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Gao G, Zhang X, Wang Z, Xu J, Wang J, Liu T, Xie Z. Multiscale insights into cornuside's effects on NAFLD: A cross-disciplinary integrating bioinformatics, computational chemistry, and machine learning. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 142:156809. [PMID: 40344848 DOI: 10.1016/j.phymed.2025.156809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 04/07/2025] [Accepted: 04/25/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a complex metabolic disorder involving intertwined signaling pathways, posing challenges for targeted therapeutic interventions. Cornus Fructus (CF), a traditional medicinal herb, holds potential for NAFLD treatment, with cornuside (COR) identified as its primary active component. METHODS This study employed a cross-disciplinary approach, integrating bioinformatics, computational chemistry, and machine learning to uncover COR's therapeutic mechanisms with precision and depth. RESULTS Using bioinformatics-driven analysis, 27 core targets were identified, revealing that COR modulated critical metabolic and inflammatory pathways. COR mitigated insulin resistance by regulating the AKT/GSK3β axis, enhanced cholesterol metabolism through LXR signaling, promoted fatty acid oxidation via PPARα activation, and suppressed inflammation by inhibiting NF-κB signaling. These results highlighted COR's ability to orchestrate multi-pathway regulation essential for restoring metabolic homeostasis in NAFLD. Molecular docking and molecular dynamics (MD) simulations provided atomistic insights, demonstrating COR's stable and high-affinity interactions with key targets. Additionally, machine learning algorithms enhanced target identification and pathway prediction, improving the precision and efficiency of the discovery process. CONCLUSION This study offered multi-scale mechanistic insights into COR's therapeutic effects on NAFLD, bridging experimental pharmacology and computational methods. The integration of bioinformatics, molecular simulation, and machine learning established a comprehensive framework for drug discovery, positioning COR as a promising candidate for NAFLD therapy and guiding future development of precision interventions.
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Affiliation(s)
- Gai Gao
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China; School of Pharmacy, Minzu University of China, Beijing 100081, China
| | - Xiaowei Zhang
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Zhenzhen Wang
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Jiangyan Xu
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China
| | - Jinghui Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China.
| | - Tongxiang Liu
- School of Pharmacy, Minzu University of China, Beijing 100081, China.
| | - Zhishen Xie
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China.
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Trifylli EM, Angelakis A, Kriebardis AG, Papadopoulos N, Fortis SP, Pantazatou V, Koskinas J, Kranidioti H, Koustas E, Sarantis P, Manolakopoulos S, Deutsch M. Extracellular vesicles as biomarkers for metabolic dysfunction-associated steatotic liver disease staging using explainable artificial intelligence. World J Gastroenterol 2025; 31:106937. [DOI: 10.3748/wjg.v31.i22.106937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/18/2025] [Accepted: 05/22/2025] [Indexed: 06/12/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally. Current diagnostic methods, such as liver biopsies, are invasive and have limitations, highlighting the need for non-invasive alternatives.
AIM To investigate extracellular vesicles (EVs) as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning (ML) and explainable artificial intelligence (XAI).
METHODS In this single-center observational study, 798 patients with metabolic dysfunction were enrolled. Of these, 194 met the eligibility criteria, and 76 successfully completed all study procedures. Transient elastography was used for steatosis and fibrosis staging, and circulating plasma EV characteristics were analyzed through nanoparticle tracking. Twenty ML models were developed: Six to differentiate non-steatosis (S0) from steatosis (S1-S3); and fourteen to identify severe steatosis (S3). Models utilized EV features (size and concentration), clinical (advanced fibrosis and presence of type 2 diabetes mellitus), and anthropomorphic (sex, age, height, weight, body mass index) data. Their performance was assessed using receiver operating characteristic (ROC)-area under the curve (AUC), specificity, and sensitivity, while correlation and XAI analysis were also conducted.
RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86 (train/test) on average across ten random five-fold cross-validations, using EV features alone to distinguish S0 from S1-S3. The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00 (train/test) on average across ten random three-fold cross-validations, using engineered features including EVs, clinical features like diabetes and advanced fibrosis, and anthropomorphic data like body mass index and weight for identifying severe steatosis (S3). Key predictors included EV mean size and concentration. Correlation, XAI, and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.
CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis (S0) in patients with metabolic dysfunction, while the combination of EV, clinical, and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis. The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights. However, further large multicenter studies, comparisons, and validation with histopathology and advanced imaging methods are needed.
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Affiliation(s)
- Eleni Myrto Trifylli
- Gastrointestinal-Liver Unit, The 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, General Hospital of Athens “Hippocratio,” Athens 11521, Greece
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica, Egaleo 12243, Attikí, Greece
| | - Athanasios Angelakis
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, Amsterdam 1105, Netherlands
- Department of Methodology, Digital Health, Amsterdam Public Health Research Institute, Amsterdam 1105, Netherlands
- Data Science Center, University of Amsterdam, Amsterdam 1098, Netherlands
| | - Anastasios G Kriebardis
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica, Egaleo 12243, Attikí, Greece
| | - Nikolaos Papadopoulos
- The Second Department of Internal Medicine, 401 General Army Hospital of Athens, Athens 11525, Greece
| | - Sotirios P Fortis
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica, Egaleo 12243, Attikí, Greece
| | - Vasiliki Pantazatou
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica, Egaleo 12243, Attikí, Greece
| | - John Koskinas
- Gastrointestinal-Liver Unit, The 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, General Hospital of Athens “Hippocratio,” Athens 11521, Greece
| | - Hariklia Kranidioti
- Gastrointestinal-Liver Unit, The 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, General Hospital of Athens “Hippocratio,” Athens 11521, Greece
| | - Evangelos Koustas
- Department of Oncology, General Hospital Evangelismos, Athens 10676, Greece
| | - Panagiotis Sarantis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Spilios Manolakopoulos
- Gastrointestinal-Liver Unit, The 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, General Hospital of Athens “Hippocratio,” Athens 11521, Greece
| | - Melanie Deutsch
- Gastrointestinal-Liver Unit, The 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, General Hospital of Athens “Hippocratio,” Athens 11521, Greece
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Wang H, Xia GQ, Ke T, Chen XX, Zhen WJ, Tian YY, Chen S, Zhang C, Li J, Zhang L, Wu DJ, Wang YT, He L, Tian WF, Wu BM. Kv1.3 knockdown attenuates alcohol-related liver injury in mice through induction of tryptamine. Acta Pharmacol Sin 2025. [DOI: 10.1038/s41401-025-01544-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 03/16/2025] [Indexed: 06/09/2025]
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Huang Y, Wan T, Hong Y, Wang X, Jiang X, Yang 杨洋 Y, Gao H, Ji J, Wang L, Yang 杨阳 Y, Li X, Wang H. Impact of NAFLD and Fibrosis on Adverse Cardiovascular Events in Patients With Hypertension. Hypertension 2025; 82:1012-1023. [PMID: 40265267 DOI: 10.1161/hypertensionaha.124.24252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 04/04/2025] [Indexed: 04/24/2025]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity in hypertension. However, the impact of NAFLD and related fibrosis on hypertension and its control of cardiovascular disease (CVD) and mortality outcomes remains unclear. METHODS Participants with hypertension were sourced from two cohorts, with 12 907 individuals from the National Health and Nutrition Examination Survey (NHANES) and 120 639 from the UK Biobank (UKBB). Mendelian randomization analyses explored the causal relationship among hypertension, NAFLD, and CVD. Cox regression models estimated the hazard ratios for CVD and mortality associated with NAFLD (defined by fatty liver index) and liver fibrosis (defined by fibrosis-4 index or NAFLD fibrosis score). RESULTS The NHANES documented 3376 deaths over a median follow-up of 8.5 years, and the UKBB documented 15 864 deaths, 4062 incident ischemic strokes, and 5314 incident myocardial infarctions over a median follow-up of 13.5 years. The hazard ratios for CVD and mortality increased in accordance with NAFLD grading (ischemic stroke, 1.16 [95% CI, 1.01-1.33]; myocardial infarction, 1.64 [95% CI, 1.44-1.86] in UKBB; and all-cause mortality, 1.29 [95% CI, 1.09-1.54] in NHANES). High-risk fibrosis increased the hazard ratios for all-cause mortality by 91% and ischemic stroke by 42% in patients with NAFLD in UKBB and for all-cause mortality by 95% in NHANES. NAFLD partially mediates the risk of hypertension for incident CVD and mortality (NHANES, 6.45% of all-cause mortality; UKBB, 5.17% of all-cause mortality; and 8.20% of myocardial infarction). CONCLUSIONS NAFLD and related liver fibrosis are associated with a higher risk of incident CVD and mortality in hypertensives. NAFLD and related liver fibrosis seem to partially mediate hypertension-induced CVD and mortality.
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Affiliation(s)
- Yanqiu Huang
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health (Y.H., T.W., Y.H., Y.Y.[], X.L., H.W.), Shanghai Jiao Tong University School of Medicine, China
| | - Tingya Wan
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health (Y.H., T.W., Y.H., Y.Y.[], X.L., H.W.), Shanghai Jiao Tong University School of Medicine, China
| | - Yuemei Hong
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health (Y.H., T.W., Y.H., Y.Y.[], X.L., H.W.), Shanghai Jiao Tong University School of Medicine, China
| | - Xiaoyu Wang
- Division of Gastroenterology and Hepatology, National Health Commission Key Laboratory of Digestive Diseases, Renji Hospital, Shanghai Institute of Digestive Disease (X.W.), Shanghai Jiao Tong University School of Medicine, China
| | - Xu Jiang
- Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University of Medicine Affiliated Ninth People's Hospital (X.J., L.W.), Shanghai Jiao Tong University School of Medicine, China
| | | | - Hong Gao
- General Practice, Community Health Center of Huaqiao Town, Suzhou, China (H.G., J.J.)
| | - Juan Ji
- General Practice, Community Health Center of Huaqiao Town, Suzhou, China (H.G., J.J.)
| | - Liao Wang
- Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University of Medicine Affiliated Ninth People's Hospital (X.J., L.W.), Shanghai Jiao Tong University School of Medicine, China
| | - Yang Yang 杨阳
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health (Y.H., T.W., Y.H., Y.Y.[], X.L., H.W.), Shanghai Jiao Tong University School of Medicine, China
- Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD (Y.Y.[])
| | - Xiaoguang Li
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health (Y.H., T.W., Y.H., Y.Y.[], X.L., H.W.), Shanghai Jiao Tong University School of Medicine, China
| | - Hui Wang
- State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health (Y.H., T.W., Y.H., Y.Y.[], X.L., H.W.), Shanghai Jiao Tong University School of Medicine, China
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Cao T, Ni X, Halengbieke A, Tang J, Han Y, Sun F, Gao B, Zheng D, Yan Y, Yang X. Effects of the triglyceride-glucose index on non-alcoholic fatty liver disease: Causal evidence from longitudinal cohort studies. Arch Gerontol Geriatr 2025; 133:105813. [PMID: 40073798 DOI: 10.1016/j.archger.2025.105813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 02/08/2025] [Accepted: 03/02/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND Insulin resistance (IR) is strongly related to non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index serves as a novel substitute indicator for IR. However, research on the effect of TyG index on NAFLD remains sparse. This study aims to investigate the causal association between TyG index and incident NAFLD. METHODS The primary cohort consisted of 27,052 participants from the Beijing Health Management Cohort, while the external validation cohort included 75,023 participants from the Taiwan MJ Cohort. Entropy balancing for continuous treatments (EBCT) combined with logistic regression and targeted maximum likelihood estimation (TMLE) were used to evaluate the causal association between the TyG index and incident NAFLD. RESULTS During a median follow-up of 2.49 years in the primary cohort, 6,168 participants (median age: 36.0 years) developed incident NAFLD. EBCT combined with logistic regression revealed the odds ratio (95 % CI) of NAFLD risk was 1.742 (1.478-2.054) for each 1-unit increase in the baseline TyG index. In the TMLE model, the risk ratio (95 % CI) for NAFLD was 1.540 (1.406-1.687) in the Q4 (quartile 4) group compared with the Q1 group. These findings were consistent with those from the external validation cohort, reinforcing the robustness of the causal relationship between the TyG index and NAFLD incidence. CONCLUSIONS The advanced double-robust estimation method suggests that a higher baseline TyG index may be causally associated with an increased NAFLD risk, providing more reliable evidence for its role as a simple biomarker and demonstrating the utility of double-robust estimation causal inference models in epidemiology.
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Affiliation(s)
- Tengrui Cao
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Xuetong Ni
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Aheyeerke Halengbieke
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Jianmin Tang
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Yumei Han
- Science and Education Section, Beijing Physical Examination Center, No. 59, Beiwei Road, Xicheng District, Beijing 100050, China.
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
| | - Bo Gao
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Deqiang Zheng
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Yuxiang Yan
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
| | - Xinghua Yang
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
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Yi H, Zhang Y, Zhou Z, Sun W, Wang Y, Tao W, Yu H, Yao L, Li J, Li L. Diagnostic Performance of Noninvasive Tests for Identifying Advanced Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease With Mixed Etiologies. Endocr Pract 2025:S1530-891X(25)00140-5. [PMID: 40334939 DOI: 10.1016/j.eprac.2025.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/10/2025] [Accepted: 04/28/2025] [Indexed: 05/09/2025]
Abstract
OBJECTIVES To assess the performance of fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and aspartate aminotransferase to platelet ratio index (APRI) for advanced fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) subgroups categorized by concomitant liver conditions. METHODS We conducted a multicentered study comprising inpatients with type 2 diabetes mellitus and MAFLD. Participants were categorized into 2 groups: MAFLD with pure metabolic etiologies (MAFLD-P) and MAFLD with mixed etiologies (MAFLD-M). Diagnostic performance of FIB-4, NFS, and APRI was assessed by area under the curve (AUC), sensitivity, and specificity. RESULTS This study comprised a total of 1475 participants, with a mean (SD) age of 58.4 (13) years and 835 (56.6%) males. FIB-4 and APRI had higher AUCs for advanced fibrosis in the MAFLD-M group than in the MAFLD-P group (MAFLD-M vs MAFLD-P: FIB-4 0.680 vs 0.591, P = .0442; APRI 0.723 vs 0.631, P = .0363). No significant difference was observed in the AUC of NFS between the 2 subgroups (MAFLD-M 0.572 vs MAFLD-P 0.617; P = .3237). Besides, the sensitivity of FIB-4 (69.6% vs 54.0%; P = .019) and APRI (43.5% vs 26.1%; P = .005) was higher in the MAFLD-M group. However, no significant difference in sensitivity of NFS and specificity of FIB-4, NFS, and APRI was observed between subgroups. CONCLUSIONS In this diagnostic study of the type 2 diabetes mellitus population, FIB-4 and APRI showed better performance for identifying advanced fibrosis in MAFLD with mixed etiologies.
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Affiliation(s)
- He Yi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China
| | - Yan Zhang
- Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, China
| | - Ziwei Zhou
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China
| | - Weixia Sun
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China
| | - Yifan Wang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China
| | - Wenxuan Tao
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China
| | - Hekai Yu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China
| | - Liqin Yao
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China.
| | - Jia Li
- Department of Ultrasound, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, China.
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Li MP, Luo KZ. The outcomes and mechanisms of chronic hepatitis B complicated by metabolic dysfunction-associated steatotic liver disease. Hepatobiliary Pancreat Dis Int 2025:S1499-3872(25)00087-6. [PMID: 40355317 DOI: 10.1016/j.hbpd.2025.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 04/24/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND In recent years, the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, given the substantial global prevalence of chronic hepatitis B (CHB), instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios. Both conditions can lead to liver fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). However, the intricacies of the dual etiology, consequential outcomes, and associated risks of CHB concurrent with MASLD are still not fully understood. DATA SOURCES A literature search was conducted on PubMed for articles published up to March 2024. The search keywords included nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic hepatitis B, liver fibrosis, hepatocellular carcinoma, nuclear factor erythroid 2-related factor 2, and oxidative stress. RESULTS This review examined recent studies on the interplay between MASLD and CHB. The coexistence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus (HBV) replication. Conversely, individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD. Nevertheless, these observations do not necessarily indicate universally positive outcomes. Indeed, MASLD and CHB may synergistically act as "co-conspirators" to exacerbate clinical manifestations, particularly liver fibrosis and HCC. CONCLUSIONS As our understanding of the interaction between steatosis and HBV infection becomes clearer, we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD. These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.
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Affiliation(s)
- Mao-Ping Li
- Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Institute of Hepatology, Central South University, Changsha 410011, China; Furong Laboratory, Changsha 410078, China
| | - Kai-Zhong Luo
- Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Institute of Hepatology, Central South University, Changsha 410011, China; Furong Laboratory, Changsha 410078, China.
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Chu Y, Yang S, Chen X. Fibroblast growth factor receptor signaling in metabolic dysfunction-associated fatty liver disease: Pathogenesis and therapeutic targets. Pharmacol Ther 2025; 269:108844. [PMID: 40113178 DOI: 10.1016/j.pharmthera.2025.108844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/08/2025] [Accepted: 02/20/2025] [Indexed: 03/22/2025]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a significant hepatic manifestation of metabolic syndrome, with its prevalence increasing globally alongside the epidemics of obesity and diabetes. MAFLD represents a continuum of liver damage, spanning from uncomplicated steatosis to metabolic dysfunction-associated steatohepatitis (MASH). This condition can advance to more severe outcomes, including fibrosis and cirrhosis. Fibroblast growth factor receptors (FGFRs) are a family of four receptor tyrosine kinases (FGFR1-4) that interact with both paracrine and endocrine fibroblast growth factors (FGFs). This interaction activates the phosphorylation of tyrosine kinase residues, thereby triggering downstream signaling pathways, including RAS-MAPK, JAK-STAT, PI3K-AKT, and PLCγ. In the context of MAFLD, paracrine FGF-FGFR signaling is predominantly biased toward the development of liver fibrosis and carcinogenesis. In contrast, endocrine FGF-FGFR signaling is primarily biased toward regulating the metabolism of bile acids, carbohydrates, lipids, and phosphate, as well as maintaining the overall balance of energy metabolism in the body. The interplay between these biased signaling pathways significantly influences the progression of MAFLD. This review explores the critical functions of FGFR signaling in MAFLD from three perspectives: first, it examines the primary roles of FGFRs relative to their structure; second, it summarizes FGFR signaling in hepatic lipid metabolism, elucidating mechanisms underlying the occurrence and progression of MAFLD; finally, it highlights recent advancements in drug development aimed at targeting FGFR signaling for the treatment of MAFLD and its associated diseases.
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Affiliation(s)
- Yi Chu
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology & College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Su Yang
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology & College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Xiaodong Chen
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology & College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
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Wong SW, Yang YY, Chen H, Xie L, Shen XZ, Zhang NP, Wu J. New advances in novel pharmacotherapeutic candidates for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) between 2022 and 2024. Acta Pharmacol Sin 2025; 46:1145-1155. [PMID: 39870846 PMCID: PMC12032127 DOI: 10.1038/s41401-024-01466-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 12/18/2024] [Indexed: 01/29/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) covers a broad spectrum of profile from simple fatty liver, evolving to metabolic dysfunction-associated steatohepatitis (MASH), to hepatic fibrosis, further progressing to cirrhosis and hepatocellular carcinoma (HCC). MASLD has become a prevalent disease with 25% in average over the world. MASH is an active stage, and requires pharmacological intervention when there is necroptotic damage with fibrotic progression. Although there is an increased understanding of MASH pathogenesis and newly approved resmetirom, given its complexity and heterogeneous pathophysiology, there is a strong necessity to develop more drug candidates with better therapeutic efficacy and well-tolerated safety profile. With an increased list of pharmaceutical candidates in the pipeline, it is anticipated to witness successful approval of more potential candidates in this fast-evolving field, thereby offering different categories of medications for selective patient populations. In this review, we update the advances in MASH pharmacotherapeutics that have completed phase II or III clinical trials with potential application in clinical practice during the latest 2 years, focusing on effectiveness and safety issues. The overview of fast-evolving status of pharmacotherapeutic candidates for MASH treatment confers deep insights into the key issues, such as molecular targets, endpoint selection and validation, clinical trial design and execution, interaction with drug administration authority, real-world data feedback and further adjustment in clinical application.
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Affiliation(s)
- Shu Wei Wong
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Yong-Yu Yang
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Hui Chen
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Li Xie
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Xi-Zhong Shen
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Ning-Ping Zhang
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
| | - Jian Wu
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
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Zhu Y, Geng SY, Chen Y, Ru QJ, Zheng Y, Jiang N, Zhu FY, Zhang YS. Machine learning algorithms reveal gut microbiota signatures associated with chronic hepatitis B-related hepatic fibrosis. World J Gastroenterol 2025; 31:105985. [PMID: 40308807 PMCID: PMC12038523 DOI: 10.3748/wjg.v31.i16.105985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/17/2025] [Accepted: 04/09/2025] [Indexed: 04/27/2025] Open
Abstract
BACKGROUND Hepatic fibrosis (HF) represents a pivotal stage in the progression and potential reversal of cirrhosis, underscoring the importance of early identification and therapeutic intervention to modulate disease trajectory. AIM To explore the complex relationship between chronic hepatitis B (CHB)-related HF and gut microbiota to identify microbiota signatures significantly associated with HF progression in CHB patients using advanced machine learning algorithms. METHODS This study included patients diagnosed with CHB and classified them into HF and non-HF groups based on liver stiffness measurements. The HF group was further subdivided into four subgroups: F1, F2, F3, and F4. Data on clinical indicators were collected. Stool samples were collected for 16S rRNA sequencing to assess the gut microbiome. Microbiota diversity, relative abundance, and linear discriminant analysis effect size (LEfSe) were analyzed in different groups. Correlation analysis between clinical indicators and the relative abundance of gut microbiota was performed. The random forest and eXtreme gradient boosting algorithms were used to identify key differential gut microbiota. The Shapley additive explanations were used to evaluate microbiota importance. RESULTS Integrating the results from univariate analysis, LEfSe, and machine learning, we identified that the presence of Dorea in gut microbiota may be a key feature associated with CHB-related HF. Dorea possibly serves as a core differential feature of the gut microbiota that distinguishes HF from non-HF patients, and the presence of Dorea shows significant variations across different stages of HF (P < 0.05). The relative abundance of Dorea significantly decreases with increasing HF severity (P = 0.041). Moreover, the gut microbiota composition in patients with different stages of HF was found to correlate with several liver function indicators, such as γ-glutamyl transferase, alkaline phosphatase, total bilirubin, and the aspartate aminotransferase/alanine transaminase ratio (P < 0.05). The associated pathways were predominantly enriched in biosynthesis, degradation/utilization/assimilation, generation of precursors, metabolites, and energy, among other categories. CONCLUSION HF affects the composition of the gut microbiota, indicating that the gut microbiota plays a crucial role in its pathophysiological processes. The abundance of Dorea varies significantly across various stages of HF, making it a potential microbial marker for identifying HF onset and progression.
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Affiliation(s)
- Ying Zhu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Shi-Yu Geng
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Yao Chen
- National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems Medicine Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou 215123, Jiangsu Province, China
| | - Qing-Jing Ru
- Department of Infectious Disease, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Yi Zheng
- Department of Infectious Disease, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Na Jiang
- Department of Infectious Disease, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Fei-Ye Zhu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Yong-Sheng Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
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11
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Wang W, Gao X, Niu W, Yin J, He K. Targeting Metabolism: Innovative Therapies for MASLD Unveiled. Int J Mol Sci 2025; 26:4077. [PMID: 40362316 PMCID: PMC12071536 DOI: 10.3390/ijms26094077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 04/01/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.
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Affiliation(s)
- Weixin Wang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; (W.W.); (W.N.)
| | - Xin Gao
- School of Public Health, Jilin University, Changchun 130021, China;
| | - Wentong Niu
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; (W.W.); (W.N.)
| | - Jinping Yin
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130041, China;
| | - Kan He
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; (W.W.); (W.N.)
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12
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Zhang W, Gao B, Wang Y, Cao Y, Wang J. The relationship between hepatic steatosis index and hypertension: NHANES 2011-2018. BMC Cardiovasc Disord 2025; 25:289. [PMID: 40247193 PMCID: PMC12004791 DOI: 10.1186/s12872-025-04744-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Accepted: 04/07/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND The Hepatic Steatosis Index (HSI) serves as a non-invasive indicator for assessing liver fat accumulation. Its potential association with hypertension has garnered increasing attention, as metabolic dysfunctions, including hepatic steatosis, may contribute to elevated blood pressure via mechanisms such as insulin resistance and chronic inflammation. METHODS Utilizing data from the NHANES database (2011-2018), the HSI was calculated on the basis of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and BMI.The association between HSI and hypertension was assessed by univariate analysis, weighted multivariate Logistic regression, and restricted cubic spline (RCS) models. Subgroup analyses were performed to increase the reliability of the data. RESULTS This cross-sectional study analysed data from 17,501 adults (NHANES 2011-2018) to assess the association between HSI and hypertension. Of these, 9,890 (56.51%) were diagnosed with hypertension.In the unadjusted model, HSI demonstrated a statistically significant correlation with hypertension, showing an odds ratio (OR) of 1.05 (95% confidence interval: 1.04-1.06).After adjustment for potential confounders, a higher prevalence of hypertension was observed in participants in the upper HSI quartiles (Q3 and Q4), with corresponding ORs of 2.29 (95% CI: 2.29-2.63) and 4.03 (95% CI: 3.42-4.74), respectively. RCS analysis revealed a U-shaped non-linear relationship between HSI and hypertension (P < 0.001), indicating that while hypertension risk primarily escalated with increasing HSI, a modest risk elevation was also detected at lower HSI levels. This suggests that both excessive liver fat accumulation (indicated by a high HSI) and underlying metabolic disorders (such as malnutrition or sarcopenia) may contribute to hypertension risk in individuals with unexpectedly low HSI. Subgroup analyses identified significant interactions in relation to education, cancer, and diabetes mellitus (p for interaction < 0.05), whereas no significant interactions were observed in other stratifications. CONCLUSION This study found a U-shaped relationship between the hepatic steatosis index (HSI) and the risk of hypertension. Although the HSI shows potential as a practical screening tool in primary care, further longitudinal studies are needed to establish causality and explore the complex bidirectional pathways involved. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Wenxuan Zhang
- Acupuncture and moxibustion and Massage College of Anhui University of Chinese Medicine, HF, China
| | - Bing Gao
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China.
| | - Yaping Wang
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China
| | - Yuxiang Cao
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China
| | - Jing Wang
- College of traditional Chinese medicine, Anhui University of Chinese Medicine, HF, China.
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, HF, China.
- Key Laboratory of Xin'an Medical Education Department, HF, China.
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13
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Reuken PA, Wagner F, Finke K, Lemhöfer C, Puta C, Stengel S, Scherag A, Lewejohann JC, Stallmach A, Quickert S. Possible link between steatotic liver diseases, severe COVID-19 and cognitive impairment in post-COVID-19 syndrome. Infection 2025:10.1007/s15010-025-02531-x. [PMID: 40208509 DOI: 10.1007/s15010-025-02531-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 03/26/2025] [Indexed: 04/11/2025]
Abstract
PURPOSE Steatotic liver diseases (SLD) have become more prevalent over the last decade and are associated not only with cardiometabolic diseases but also with psychological symptoms (depression, fatigue). These symptoms are also common in post-COVID syndrome (PCS). Therefore, the aim of the study was to analyze the burden of SLD in PCS patients. METHODS We systematically screened all PCS patients from our post-COVID outpatient clinic using transient elastography, structured questionnaires for neurocognitive evaluation and blood sample analysis. Controls without PCS and without known liver diseases were also recruited and assessed with the same approach. RESULTS 560 PCS patients and 103 healthy controls were included. The overall prevalence of SLD was high in both cohorts (57 vs. 53%). PCS patients with SLD were more frequently male (41 vs. 24%), older (52 vs. 44 years) and had more cardiometabolic diseases (87.0 vs. 46.4%). Cognitive impairment was more related to SLD in PCS patients than in the no-SLD group (OR: 1.68, CI: 1.14-2.46, p = 0.008). The presence of SLD was related to severe COVID-19 with hospitalization (OR: 2.91, CI: 1.85-4.56, p < 0.001). Within 1 year of the follow-up, 152 of 289 patients described a resolution in PCS irrespective of the presence or absence of SLD (log-rank p = 0.96). CONCLUSIONS SLD is associated with severe COVID-19 and cognitive dysfunction in PCS. Longitudinal studies are needed to assess the role of hepatic steatosis, development of post-acute infection regulation (e.g., SARS-CoV-2) and to differentiate between SLD-associated symptoms and PCS.
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Affiliation(s)
- Philipp A Reuken
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Freya Wagner
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Kathrin Finke
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany
- Department of Neurology, Jena University Hospital, Jena, Germany
| | - Christina Lemhöfer
- Institute of Physical and Rehabilitation Medicine, Jena University Hospital, Jena, Germany
| | - Christian Puta
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany
- Department of Sports Medicine and Health Promotion, Friedrich-Schiller-University Jena, Jena, Germany
| | - Sven Stengel
- Department of Neuropediatrics, Jena University Hospital, Jena, Germany
| | - André Scherag
- Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany
| | | | - Andreas Stallmach
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Stefanie Quickert
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.
- Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
- Interdisciplinary Centre for Clinical Research (IZKF) Jena, Jena University Hospital, Jena, Germany.
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14
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Bai C, Song X, Yan J, Xu J, Zhou Y, Sun Z, Zheng Q, Zhang Y, Chen R, Jin X, Shao Y, Xie Y, Yang L, Zhong F, Zhang Y, Li J, Li R, Yan S, Li X. Tauroursodeoxycholic Acid Induces Liver Regeneration and Alleviates Fibrosis Through GATA3 Activation. Biomedicines 2025; 13:910. [PMID: 40299532 PMCID: PMC12024728 DOI: 10.3390/biomedicines13040910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/07/2025] [Accepted: 03/11/2025] [Indexed: 04/30/2025] Open
Abstract
Background: Liver regeneration is a critical measure of liver health and plays an essential role in inhibiting the progression of fibrotic lesions and preventing liver failure after hepatocellular carcinoma surgery. However, there are no approved drugs to address this clinical challenge. Methods: The effects of TUDCA on liver regeneration and fibrosis were studied using BRL-3A cells, a partial hepatectomy (PH) rat liver regeneration model, and a carbon tetrachloride (CCl4)-induced liver fibrosis model. GATA3-knockdown BRL-3A cells were employed to assess the role of GATA3 in TUDCA-induced proliferation. Results: TUDCA promoted the proliferation of BRL-3A cells and enhanced liver regeneration in PH rats while ameliorating liver fibrosis in CCl4-treated rats. Additionally, the knockdown of GATA3 eliminated the proliferative effect of TUDCA on BRL-3A cells. Conclusions: TUDCA promotes liver regeneration and alleviates liver fibrosis by activating GATA3.
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Affiliation(s)
- Chongyang Bai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Xiaojing Song
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China
- National Clinical Key Specialty of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China
- Hepatopancreatobiliary Surgery Institute of Gansu Province, Lanzhou 730000, China
- Clinical Research Center for General Surgery of Gansu Province, Lanzhou 730000, China
| | - Jiexi Yan
- Precision Medicine Laboratory, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Jun Xu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
- Department of Vascular Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Yongqiang Zhou
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Zongbin Sun
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Qiuxia Zheng
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Yue Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Ruixi Chen
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Xiaoyi Jin
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Yi Shao
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Yande Xie
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Lele Yang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Fupeng Zhong
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Yuting Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Jiatai Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Runfeng Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Shaolin Yan
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
| | - Xun Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China
- National Clinical Key Specialty of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China
- Hepatopancreatobiliary Surgery Institute of Gansu Province, Lanzhou 730000, China
- Clinical Research Center for General Surgery of Gansu Province, Lanzhou 730000, China
- Precision Medicine Laboratory, The First Hospital of Lanzhou University, Lanzhou 730000, China
- Cancer Prevention and Treatment Center of Lanzhou University School of Medicine, Lanzhou 730000, China
- Key Laboratory Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou 730000, China
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15
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Tang Y, Deng Y, Zhang G, Wang Y, Wang J, Wu J, Gu M. Inflammatory markers as predictors of liver fibrosis in type 2 diabetes patients with metabolic dysfunction-associated fatty liver disease. Front Endocrinol (Lausanne) 2025; 16:1556646. [PMID: 40265164 PMCID: PMC12011603 DOI: 10.3389/fendo.2025.1556646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/11/2025] [Indexed: 04/24/2025] Open
Abstract
Objective This study investigates the link between inflammatory markers and liver fibrosis in type 2 diabetes mellitus (T2DM) patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods From Oct 2020 to Oct 2024, 769 hospitalized T2DM patients were studied. They were split into Control (n=389) and Experimental groups (T2DM with MAFLD, n=380). The Experimental group was further divided based on FIB-4 scores into non-fibrosis (FIB-4< 1.3, n=267), suspected fibrosis (1.3 ≤ FIB-4 ≤ 2.67, n=99), and advanced fibrosis (FIB-4 > 2.67, n=14). Logistic regression identified factors affecting liver fibrosis, while ROC analysis assessed the predictive value of NLR, SIRI, PLR, and PHR for liver fibrosis in T2DM-MAFLD patients. Results The Experimental group showed higher BMI, FPG, TG, TC, LDL-C, ALT, AST, ALB, GGT, and SUA, but lower age, diabetes duration, MPV, and HDL-C (P< 0.05). Compared to non-fibrosis, suspected fibrosis had higher age, diabetes duration, MPV, AST, and NLR, and lower LY, PLR, PHR. Advanced fibrosis featured higher age, AST, NLR, FPG, HbA1c, SIRI, and lower LY, RBC, LDL-C, PLR, PHR, Hb, PLT, and ALB (P< 0.05). Logistic regression identified NLR, SIRI, PLR, and PHR as significant factors for liver fibrosis. ROC analysis showed AUCs of 0.712 (NLR), 0.757 (SIRI), 0.703 (PLR), and 0.806 (PHR) with sensitivities and specificities varying among markers. Optimal cut-offs were 1.573 (NLR), 1.465 (SIRI), 110.819 (PLR), and 185.379 (PHR). Conclusions NLR, SIRI, PLR, and PHR significantly influence liver fibrosis in T2DM patients with MAFLD, aiding in its diagnosis and management.
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Affiliation(s)
- Yange Tang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Yulong Deng
- Department of Orthopaedics and Traumatology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Gengliang Zhang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Yanjun Wang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Jing Wang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Jie Wu
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Mengjin Gu
- Department of Anesthesiology, Zhengding County People’s Hospital, Shijiazhuang, China
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Zhang R, Wang J, Liu T, Wang Y, Yang S, Yan F, Xue L. Proof of Concept: Super-Resolution Ultrasound and Viscoelastic Imaging of Hepatic Microcirculation for Early Detection and Staging of Liver Fibrosis in a Murine Model. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2025. [PMID: 40197694 DOI: 10.1002/jum.16703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 03/24/2025] [Accepted: 03/28/2025] [Indexed: 04/10/2025]
Abstract
OBJECTIVES Super-resolution ultrasound microvascular imaging (SRUS) has emerged as a noninvasive technology capable of visualizing the microvasculature with exceptional spatial resolution, surpassing the acoustic diffraction limit. This study aims to assess the potential of SRUS in staging liver fibrosis by evaluating its diagnostic performance against ultrasound viscosity imaging. METHODS Liver fibrosis was induced by carbon tetrachloride (CCl4) in 30 mice. The mice were evenly distributed across five stages (6 mice per stage), categorized from F0 (no fibrosis) to F4 (cirrhosis) based on the extent of collagen deposition. SRUS microvascular imaging and ultrasound viscosity imaging were compared for their efficacy in detecting liver fibrosis stages. Immunohistochemistry and histopathological analyses were conducted to correlate vessel density and collagen deposition. RESULTS SRUS effectively detected microvascular changes across all fibrosis stages. Significant vessel diameter enlargement was observed at early stages (F1), with further increases in advanced stages (F3-F4). Vessel density significantly decreased in later stages, indicating compromised angiogenesis. Ultrasound viscosity imaging showed marked viscoelastic reductions in fibrosis but lacked sensitivity in early-stage detection. SRUS parameters exhibited strong correlations with histological findings, underscoring their potential diagnostic value. Receiver operating characteristic (ROC) curve analysis further demonstrated the superior sensitivity of SRUS (89.59% [95% confidence interval (CI): 84.87-92.96%]), particularly in distinguishing early-stage fibrosis (F0-F1) from advanced stages (F2-F4) (area under the curve [AUC] = 0.9610, 95% CI: 0.9449-0.9771; P < .001). CONCLUSIONS SRUS microvascular imaging is a promising adjunct to traditional elastography, offering enhanced sensitivity for early-stage liver fibrosis detection. It provides critical insights into microcirculatory dysfunction, complementing stiffness measurements and aiding in accurate diagnosis.
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Affiliation(s)
- Rui Zhang
- Department of Cardiovascular Ultrasound, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jieqiong Wang
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Tingting Liu
- Ultrasonic Medicine, Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Yan Wang
- Department of Cardiovascular Ultrasound, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shuai Yang
- Department of Clinical and Research, Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China
| | - Fei Yan
- Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Li Xue
- Department of Cardiovascular Ultrasound, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
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17
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Man S, Zu Y, Yang X, Deng Y, Shen D, Ma Y, Fu J, Du J, Yu C, Lv J, Li G, Wang B, Li L. Prevalence of Elevated Lipoprotein(a) and its Association With Subclinical Atherosclerosis in 2.9 Million Chinese Adults. J Am Coll Cardiol 2025:S0735-1097(25)05277-5. [PMID: 40266173 DOI: 10.1016/j.jacc.2025.02.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/24/2025] [Accepted: 02/27/2025] [Indexed: 04/24/2025]
Abstract
BACKGROUND Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased risk of atherosclerotic cardiovascular disease; yet, large-scale studies on the epidemiology of elevated Lp(a) as well as its association with subclinical atherosclerosis in the Chinese population are limited. OBJECTIVES This study aimed to estimate the prevalence of elevated Lp(a) in a large check-up population of China, and investigate its associations with both site-specific and multisite subclinical atherosclerosis. METHODS Adults who underwent Lp(a) testing between 2017 and 2023 at Meinian health check-up centers in 30 provinces of China were included. Because the test results of Lp(a) were reported in either the mass unit (mg/dL) or the molar unit (nmol/L) and conversion between units was not recommended, separate analyses were conducted for each unit. Subclinical atherosclerosis was assessed using various imaging examinations at the carotid artery, the brain, and the coronary artery. The prevalence of elevated Lp(a) was estimated across the overall study population and various subpopulations. The logistic regression model was used to investigate the associations between elevated Lp(a) and subclinical atherosclerosis. RESULTS A total of 2,788,206 and 167,114 participants with the mass unit and the molar unit were included. In the mass unit group, the prevalence of Lp(a) >30 and >50 mg/dL was 18.67% and 8.41%, respectively. Significantly higher prevalence was observed among women, elderly individuals, and individuals with various cardio-renal-metabolic risk factors (all P < 0.05). Compared with Lp(a) ≤30 mg/dL, individuals with Lp(a) >30 to ∼50 mg/dL exhibited 11%, 15%, 9%, and 11% greater odds of increased carotid intima-media thickness, carotid plaque, subclinical brain infarcts, and coronary artery calcification, respectively. The odds were even higher for those with Lp(a) >50 mg/dL. Furthermore, elevated Lp(a) was significantly associated with the extent of coronary artery calcification, as well as subclinical atherosclerosis at 1, 2, and 3 sites, with the association being more pronounced in cases with severe extent and multisite involvement. These results were similar in the molar unit group. CONCLUSIONS A significant burden of elevated Lp(a) was found in China, highlighting the necessity of prioritized Lp(a) screening in high-risk groups. Elevated Lp(a) was identified as a significant risk factor for site-specific subclinical atherosclerosis, with stronger associations observed in severe extent and multisite involvement. Our findings suggest that individuals with elevated Lp(a) should undergo a comprehensive assessment of subclinical atherosclerosis at multiple sites to help prevent ASCVD.
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Affiliation(s)
- Sailimai Man
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Meinian Institute of Health, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Yining Zu
- Meinian Institute of Health, Beijing, China
| | - Xiaochen Yang
- Meinian Institute of Health, Beijing, China; Department of Social Medicine and Health Education, School of Public Health, Peking University, Beijing, China
| | - Yuhan Deng
- Chongqing Research Institute of Big Data, Peking University, Chongqing, China
| | - Dan Shen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Yuan Ma
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingzhu Fu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jing Du
- Beijing Center for Disease Prevention and Control, Beijing, China
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing, China.
| | - Gang Li
- Beijing Center for Disease Prevention and Control, Beijing, China; School of Public Health, Capital Medical University, Beijing, China.
| | - Bo Wang
- Meinian Institute of Health, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China
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Liu Z, Huang J, Dai L, Yuan H, Jiang Y, Suo C, Jin L, Zhang T, Chen X. Steatotic Liver Disease Prevalence in China: A Population-Based Study and Meta-Analysis of 17.4 Million Individuals. Aliment Pharmacol Ther 2025; 61:1110-1122. [PMID: 40013739 DOI: 10.1111/apt.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/20/2024] [Accepted: 02/16/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND Steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), has emerged as a leading cause of chronic liver disease in China. AIMS We aimed to provide a comprehensive and updated description of SLD prevalence in China. METHODS We described the prevalence, subgroup distribution, and clinical characteristics of SLD in the Taizhou Study of Liver Diseases (T-SOLID). Additionally, we searched for studies reporting SLD prevalence in five databases. Eligible data were analysed using a generalised linear mixed model. Linear regression was applied to estimate the annual average percentage change (AAPC). RESULTS Of the 28,623 participants in T-SOLID, 30.8% were diagnosed with SLD, among which 83.8% were classified as MASLD. Prevalence of SLD increased from 22.1% in 2018 to 36.7% in 2021. The meta-analysis included 792 publications and 17,404,296 subjects. Nationwide, the pooled SLD prevalence rose from 23.8% (95% CI 21.9%-25.9%) during 2001-2010 to 27.9% (26.0%-29.8%) during 2016-2023 in the general population (AAPC = 2.56, p < 0.0001), equating to approximately 402.0 million cases. An increase in SLD prevalence was observed in subpopulations by region, sex, and age, and in high-risk groups. Northeast China had the highest prevalence (35.0%). Males had a higher prevalence rate than females (35.0% vs. 20.6%). SLD prevalence increased with age, ranging from 8.1% in children and adolescents to 31.8% in the elderly. Meta-regression identified calendar period, age, sex, geographical area, and residence area as significant determinants of SLD prevalence. CONCLUSION The ubiquitously rising prevalence of SLD in Chinese populations underscores the urgent need for targeted public health interventions.
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Affiliation(s)
- Zhenqiu Liu
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Jiayi Huang
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Luojia Dai
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Huangbo Yuan
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Li Jin
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
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Guan L, Zhang X, Liu S, Qi X, Li Y. Prevalence of steatotic liver disease and associated fibrosis in the general population: An epidemiological survey: Letter to the editor on "Epidemiology of metabolic dysfunction-associated steatotic liver disease". Clin Mol Hepatol 2025; 31:e145-e148. [PMID: 39468843 PMCID: PMC12016584 DOI: 10.3350/cmh.2024.0921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 10/30/2024] Open
Affiliation(s)
- Lin Guan
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xinhe Zhang
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shanghao Liu
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Yiling Li
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
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Ding D, Jia G, Guo G, Cui L, Han Y. Risk stratification for patients with primary biliary cholangitis: early versus advanced-stage or non-cirrhosis versus cirrhosis? Hepatol Int 2025:10.1007/s12072-025-10820-8. [PMID: 40155490 DOI: 10.1007/s12072-025-10820-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 03/07/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is divided into early and advanced stages, which are two distinct disease states, and whether this division is optimal remains to be demonstrated. AIMS A risk stratification strategy was re-established according to histological stages and response criteria were defined accordingly. METHODS We retrospectively analyzed 721 patients with histological data. The endpoint events were liver-related death and liver transplantation (LT). RESULTS Histological stage IV was associated with LT-free survival compared to stage III (HR: 2.764, 95% CI: 1.457-5.247, p = 0.002); and stage III was not associated with LT-free survival compared to stage II (HR: 1.632, 95% CI: 0.833-3.195, p = 0.153). Total bilirubin was associated with LT-free survival (HR: 1.162, 95% CI: 1.079-1.251, p < 0.001), whereas alkaline phosphatase was not associated with LT-free survival in cirrhotic patients (HR: 1.256, 95% CI: 0.958-1.648, p = 0.100). Compared to Paris I, Paris II, and Toronto, Rotterdam had the highest area under the receiver operating characteristic curve (AUC) for predicting the 5-year endpoint events in cirrhotic patients (0.652 [0.558-0.745]). Patients who had poor response according to Rotterdam criteria had worse prognosis than those who were biochemical responders (p = 0.036). Compared to Paris II and Paris I (for stage III) + Paris II (for stage I-II), Paris I, Rotterdam, and Toronto had higher AUC in non-cirrhotic patients (p < 0.05). CONCLUSIONS Risk stratification based on histological classification of non-cirrhosis versus cirrhosis demonstrates superior clinical utility compared to the early versus advanced stage stratification. Furthermore, the Rotterdam criteria proved to be clinically applicable for assessing biochemical responses specifically in patients with histological cirrhosis.
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Affiliation(s)
- Dawei Ding
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Gui Jia
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Guanya Guo
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Lina Cui
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Ying Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China.
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De Rosa L, Ricco G, Brunetto MR, Bonino F, Faita F. Sustainability of General Population Screening for Steatotic Liver Disease: A Proof-of-Concept Study. Healthcare (Basel) 2025; 13:759. [PMID: 40218056 PMCID: PMC11989194 DOI: 10.3390/healthcare13070759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/19/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Steatotic liver disease (SLD) is a growing global health concern and may progress to more advanced liver diseases (i.e., fibrosis, cirrhosis, and hepatocellular carcinoma). Early identification of individuals at risk through effective screening strategies is crucial for timely intervention and management. The aim of this population-based study was to evaluate the feasibility of mean/large-scale screening and its importance by analyzing key risk factors, such as metabolic and lifestyle-related determinants. METHODS This cross-sectional study involved 387 subjects aged 18 to 89 years in a remote rural area that stretches among the valleys at the foot of the Apennines and the Apuan Alps. Anthropometric and demographic data were recorded, together with the measurement of blood pressure and cardiac rhythm. Furthermore, US-based liver stiffness (LS) and the ultrasound attenuation parameter (UAP) using the ILivTouch (Hisky Medical, Wuxi, China) device were performed. All data were analyzed with SPSS version 28. Univariate and multivariate analyses were conducted to identify significant predictors of both LS and UAP. RESULTS Significant associations are observed between elevated LS and UAP values and risk factors, such as BMI and waist circumference (BMI and waist with R = 0.45 and R = 0.34, R = 0.29 and R = 0.28; respectively, for UAP and LS; all with p < 0.001). The presence of hypertension is associated with a high value of LS (p < 0.05), and high UAP with alcohol consumption and sugary coffee intake habit (p < 0.001 and, p < 0.05, respectively). CONCLUSIONS General population screening for SLD is feasible, sustainable, and useful to identify both individuals at risk and patients with progressive liver disease.
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Affiliation(s)
- Laura De Rosa
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy;
| | - Gabriele Ricco
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa (AOUP), 56124 Pisa, Italy; (G.R.); (M.R.B.)
| | - Maurizia Rossana Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa (AOUP), 56124 Pisa, Italy; (G.R.); (M.R.B.)
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Ferruccio Bonino
- Institute of Biostructure and Bioimaging, National Research Council, Via De Amicis 95, 80145 Naples, Italy;
| | - Francesco Faita
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy;
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Zhao Z, Zhu Y, Wan D. Exercise and tissue fibrosis: recent advances in therapeutic potential and molecular mechanisms. Front Endocrinol (Lausanne) 2025; 16:1557797. [PMID: 40182630 PMCID: PMC11965137 DOI: 10.3389/fendo.2025.1557797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/24/2025] [Indexed: 04/05/2025] Open
Abstract
Tissue fibrosis represents an aberrant repair process, occurring because of prolonged injury, sustained inflammatory response, or metabolic disorders. It is characterized by an excessive accumulation of extracellular matrix (ECM), resulting in tissue hardening, structural remodeling, and loss of function. This pathological phenomenon is a common feature in the end stage of numerous chronic diseases. Despite the advent of novel therapeutic modalities, including antifibrotic agents, these have only modest efficacy in reversing established fibrosis and are associated with adverse effects. In recent years, a growing body of research has demonstrated that exercise has significant benefits and potential in the treatment of tissue fibrosis. The anti-fibrotic effects of exercise are mediated by multiple mechanisms, including direct inhibition of fibroblast activation, reduction in the expression of pro-fibrotic factors such as transforming growth factor-β (TGF-β) and slowing of collagen deposition. Furthermore, exercise has been demonstrated to assist in maintaining the dynamic equilibrium of tissue repair, thereby indirectly reducing tissue damage and fibrosis. It can also help maintain the dynamic balance of tissue repair by improving metabolic disorders, exerting anti-inflammatory and antioxidant effects, regulating cellular autophagy, restoring mitochondrial function, activating stem cell activity, and reducing cell apoptosis, thereby indirectly alleviating tissue. This paper presents a review of the therapeutic potential of exercise and its underlying mechanisms for the treatment of a range of tissue fibrosis, including cardiac, pulmonary, renal, hepatic, and skeletal muscle. It offers a valuable reference point for non-pharmacological intervention strategies for the comprehensive treatment of fibrotic diseases.
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Affiliation(s)
- Zheng Zhao
- School of Physical Education, Anyang Normal University, Anyang, Henan, China
| | - Yongjia Zhu
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
| | - Dongfeng Wan
- School of Health, Shanghai Normal University Tianhua College, Shanghai, China
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Liu Z, Gao H, Yan W, Li S, Jiang W, Wang Y, Jiang Y, You C. Clinical application of bile acid profile combined with lipid indices in metabolic dysfunction-associated steatotic liver disease. Clin Chim Acta 2025; 570:120217. [PMID: 40015498 DOI: 10.1016/j.cca.2025.120217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 02/21/2025] [Accepted: 02/24/2025] [Indexed: 03/01/2025]
Abstract
OBJECTIVE This study aims to investigate the diagnostic potential of bile acid profiles combined with lipid parameters in metabolic dysfunction-associated steatotic liver disease (MASLD). METHOD This study employed LC-MS technology to analyze the serum bile acid profiles of 186 male patients with MASLD and 80 male non-MASLD patients. According to whether the serum samples exhibit dyslipidemia, the subjects were divided into four groups. Subsequently, a series of analyses were conducted, including univariate analysis, the Spearman correlation test, multinomial logistic regression, restricted cubic spline regression, and ROC curve analysis. RESULT The bile acid profiles of serum samples with dyslipidemia exhibit significant differences compared to those of normal serum samples. The bile acids, which include total deoxycholic acid (DCA), secondary bile acids (SBA), unconjugated bile acids (UCBA), 12α-hydroxylated bile acids (12HBA), total bile acids (TBA), primary bile acids (PBA)/SBA, and glycine-conjugated bile acids (GCBA)/taurine-conjugated bile acids (TCBA), demonstrate a non-linear correlation with the logarithmic ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C). The ROC analysis indicates that, in populations with normal lipid levels, bile acid indicators such as GLCA and 12HBA demonstrate a superior ability to distinguish between MASLD and non-MASLD compared to populations with abnormal lipid levels and the overall population. Their diagnostic performance significantly surpasses that of existing MASLD diagnostic models. CONCLUSION The combination of bile acid profiles and lipid indicators holds significant diagnostic potential in MASLD.
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Affiliation(s)
- Zhenhua Liu
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Hongwei Gao
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Wen Yan
- Healthy Management Centre, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Simin Li
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Wenwen Jiang
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Yingying Wang
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Yao Jiang
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China
| | - Chongge You
- Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 Gansu Province, China.
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Deng L, Huang J, Yuan H, Liu Q, Lou W, Yu P, Xie X, Chen X, Yang Y, Song L, Deng L. Biological age prediction and NAFLD risk assessment: a machine learning model based on a multicenter population in Nanchang, Jiangxi, China. BMC Gastroenterol 2025; 25:172. [PMID: 40082778 PMCID: PMC11908037 DOI: 10.1186/s12876-025-03752-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 03/03/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND The objective was to develop a biological age prediction model (NC-BA) for the Chinese population to enrich the relevant studies in this population. And to investigate the association between accelerated age and NAFLD. METHODS On the basis of the physical examination data of people without noninfectious chronic diseases (PWNCDs) in Nanchang, Jiangxi, China, the biological age measurement method was developed via three feature selection methods (all-subset regression, LASSO regression (LR), and recursive feature elimination) and three machine learning algorithms (generalized linear model (GLM), support vector machine, and deep generalized linear model (deep GLM)). Model performance was evaluated by the coefficient of determination (R²) and mean absolute error (MAE). National Health and Nutrition Examination Survey (NHANES) data were used to verify the model's generalizability. The standardized age deviation (SAD) was calculated to explore the associations between age acceleration and the risk of morbidity and mortality from NAFLD. RESULTS The physical examination data of 26,356 PWNCDs were collected in Nanchang. Among the 26 biomarkers, 26 and 24 biomarkers were associated with chronological age in the male and female groups, respectively (P < 0.05). The model combining the LR and deep GLM algorithms provided the most accurate measurement of chronological age (r = 0.58, MAE = 5.33) and was named the Nanchang-biological age (NC-BA) model. The generalizability of the NC-BA model was verified in the NHANES dataset (r = 0.57, MAE = 7.12). There was a significant correlation between NC-BA and existing biological age indicators (Klemera-Doubal method biological age (KDM-BA), PhenoAge, and homeostatic dysregulation (HD), r = 0.42-0.66, P < 0.05). The physical examination data of 1,663 and 1,445 patients with NAFLD from the Nanchang population and NHANES, respectively, were obtained. The SAD values of NAFLD patients were significantly greater than those of PWNCDs (P < 0.001). The SAD values of NAFLD patients with younger chronological ages were greater (P < 0.001). Higher SAD values were associated with a greater risk of all-cause mortality (HR = 1.73, P = 0.005). CONCLUSIONS This study provides a new model for biological age measurement in the Chinese population. There is a clear link between NAFLD and age acceleration.
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Affiliation(s)
- Lianrui Deng
- Affiliated Rehabilitation Hospital of Nanchang University, Nanchang, China
| | - Jing Huang
- School of Public Health, Jiangxi Medical College, Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, China
| | - Hang Yuan
- Chaisang District Center for Disease Control and Prevention, Jiujiang, China
| | - Qiangdong Liu
- Center of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- The Institute of Periodontal Disease, JXHC Key Laboratory of Periodontology (The Second Affiliated Hospital of Nanchang University), Nanchang University, Nanchang, China
| | - Weiming Lou
- The Institute of Periodontal Disease, JXHC Key Laboratory of Periodontology (The Second Affiliated Hospital of Nanchang University), Nanchang University, Nanchang, China
| | - Pengfei Yu
- Big Data Research Center, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xiaohong Xie
- Sanming City Shaxian District General Hospital, Nanchang, China
| | - Xuyu Chen
- Physical Examination Center, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yang Yang
- Physical Examination Center, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Li Song
- Center of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
- The Institute of Periodontal Disease, JXHC Key Laboratory of Periodontology (The Second Affiliated Hospital of Nanchang University), Nanchang University, Nanchang, China.
| | - Libin Deng
- School of Public Health, Jiangxi Medical College, Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, China.
- The Institute of Periodontal Disease, JXHC Key Laboratory of Periodontology (The Second Affiliated Hospital of Nanchang University), Nanchang University, Nanchang, China.
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Liu X, Xing Y, Zu Y, Bao H, Ding X, Chen Y, Yu C, Lyu J, Wang L, Wang B, Man S, Li L, Liu H. Detection and BI-RADS Classification of Breast Nodules in Urban Women - China, 2021. China CDC Wkly 2025; 7:347-352. [PMID: 40225779 PMCID: PMC11982918 DOI: 10.46234/ccdcw2025.056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 02/26/2025] [Indexed: 04/15/2025] Open
Abstract
What is already known about this topic? Female breast nodules represent the most frequently detected lesions during breast ultrasound screening. Notably, nodules classified as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 indicate an elevated risk of breast cancer. Nevertheless, the detection rate and BI-RADS classification of female breast nodules in China remain largely undocumented. What is added by this report? In 2021, breast nodules were detected in 27.9% of urban women in China. Among women with breast nodules marked with BI-RADS classification information, 95.9% were categorized as BI-RADS 2-3, while 4.0% were classified as BI-RADS 4-5. Age, geographic location, per capita gross domestic product (GDP), body mass index (BMI), high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and diabetes were identified as risk factors for BI-RADS 4-5. What are the implications for public health practice? This study highlights the importance of managing high-risk women with breast nodules through BI-RADS classification. Women with older age, high TG, high LDL-C, or diabetes demonstrate higher detection rates of BI-RADS 4-5, underscoring the need for targeted health interventions for high-risk populations while accounting for regional and socioeconomic disparities.
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Affiliation(s)
- Xiaoxi Liu
- Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China
| | - Yaxin Xing
- Peking Union Medical College, Beijing, China
| | - Yining Zu
- Meinian Institute of Health, Beijing, China
| | - Heling Bao
- Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China
| | - Xue Ding
- Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China
| | - Yongchao Chen
- Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China
| | - Canqing Yu
- Peking University Health Science Center Meinian Public Health Institute, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China
| | - Jun Lyu
- Peking University Health Science Center Meinian Public Health Institute, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China
| | - Linhong Wang
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Bo Wang
- Meinian Institute of Health, Beijing, China
- Peking University Health Science Center Meinian Public Health Institute, Beijing, China
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China
| | - Sailimai Man
- Meinian Institute of Health, Beijing, China
- Peking University Health Science Center Meinian Public Health Institute, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Liming Li
- Peking University Health Science Center Meinian Public Health Institute, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China
| | - Hui Liu
- Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China
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Xiong FX, Sun L, Zhang XJ, Chen JL, Zhou Y, Ji XM, Meng PP, Wu T, Wang XB, Hou YX. Machine learning-based models for advanced fibrosis in non-alcoholic steatohepatitis patients: A cohort study. World J Gastroenterol 2025; 31:101383. [PMID: 40061588 PMCID: PMC11886044 DOI: 10.3748/wjg.v31.i9.101383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/02/2024] [Accepted: 01/08/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND The global prevalence of non-alcoholic steatohepatitis (NASH) and its associated risk of adverse outcomes, particularly in patients with advanced liver fibrosis, underscores the importance of early and accurate diagnosis. AIM To develop a machine learning-based diagnostic model for advanced liver fibrosis in NASH patients. METHODS A total of 749 patients who underwent liver biopsy at Beijing Ditan Hospital, Capital Medical University, between January 2010 and January 2020 were included. Patients were randomly divided into training (n = 522) and validation (n = 224) cohorts. Five machine learning models were applied to predict advanced liver fibrosis, with feature selection based on Shapley Additive Explanations (SHAP). The diagnostic performance of these models was compared to traditional scores such as the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4), using metrics including the area under the receiver operating characteristic curve (AUROC), decision curve analysis (DCA), and calibration curves. RESULTS The Extreme Gradient Boosting (XGBoost) model outperformed all other machine learning models, achieving an AUROC of 0.934 (95%CI: 0.914-0.955) in the training cohort and 0.917 (95%CI: 0.880-0.953) in the validation cohort (P < 0.001). Incorporating liver stiffness measurement into the model further improved its performance, with an AUROC of 0.977 (95%CI: 0.966-0.980) in the training cohort and 0.970 (95%CI: 0.950-0.990) in the validation cohort, significantly surpassing APRI and FIB-4 scores (P < 0.001). The XGBoost model also demonstrated superior clinical utility, as evidenced by DCA and calibration curve analysis in both cohorts. CONCLUSION The XGBoost model provides a highly accurate, non-invasive diagnosis of advanced liver fibrosis in NASH patients, outperforming traditional methods. An online tool based on this model has been developed to assist clinicians in evaluating the risk of advanced liver fibrosis.
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Affiliation(s)
- Fei-Xiang Xiong
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Lei Sun
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
- Department of Pathology, Beijing Ditan Hospital, Beijing 100015, China
| | - Xue-Jie Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Jia-Liang Chen
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yang Zhou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Min Ji
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Pei-Pei Meng
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Tong Wu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xian-Bo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yi-Xin Hou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Zhang JW, Zhang N, Lyu Y, Zhang XF. Influence of Sex in the Development of Liver Diseases. Semin Liver Dis 2025; 45:15-32. [PMID: 39809453 DOI: 10.1055/a-2516-0261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
The liver is a sexually dimorphic organ. Sex differences in prevalence, progression, prognosis, and treatment prevail in most liver diseases, and the mechanism of how liver diseases act differently among male versus female patients has not been fully elucidated. Biological sex differences in normal physiology and disease arise principally from sex hormones and/or sex chromosomes. Sex hormones contribute to the development and progression of most liver diseases, with estrogen- and androgen-mediated signaling pathways mechanistically involved. In addition, genetic factors in sex chromosomes have recently been found to contribute to the sex disparity of many liver diseases, which might explain, to some extent, the difference in gene expression pattern, immune response, and xenobiotic metabolism between men and women. Although increasing evidence suggests that sex is one of the most important modulators of disease prevalence and outcomes, at present, basic and clinical studies have long been sex unbalanced, with female subjects underestimated. As such, this review focuses on sex disparities of liver diseases and summarizes the current understanding of sex-specific mechanisms, including sex hormones, sex chromosomes, etc. We anticipate that understanding sex-specific pathogenesis will aid in promoting personalized therapies for liver disease among male versus female patients.
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Affiliation(s)
- Jie-Wen Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | - Nan Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | - Yi Lyu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
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28
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Yang C, Zhang H, Tian J, Li Z, Liu R, Huang G, Zhao L. Structural alteration of hippocampal subfields in type 2 diabetes mellitus patients with dyslipidemia. Brain Res 2025; 1850:149368. [PMID: 39622483 DOI: 10.1016/j.brainres.2024.149368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/11/2024] [Accepted: 11/28/2024] [Indexed: 12/14/2024]
Abstract
OBJECTIVE To explore alterations in hippocampal subfield volumes in type 2 diabetes mellitus (T2DM) patients with dyslipidemia using hippocampal subfield segmentation. METHODS A total of 99 T2DM patients were prospectively recruited and divided into two groups based on the presence or absence of dyslipidemia: the T2DM dyslipidemia group and the T2DM normal lipidemia group. Additionally, 57 healthy volunteers were recruited as the healthy control (HC) group. General clinical data and cognitive psychological scale scores were collected. Subgroup analyses of T2DM patients were conducted based on the presence or absence of mild cognitive impairment (MCI). Hippocampal subfield volumes were analyzed using a general linear model with post-hoc Bonferroni correction. Significant differential hippocampal subfields were further analyzed in subgroups using the general linear model with post-hoc Bonferroni tests. Partial correlation analyses were performed to assess correlations between subfield-specific volumes and lipid and glucose metabolism indicators, as well as cognitive psychological scale scores. P-values from partial correlation analyses were corrected using the false discovery rate (FDR). RESULTS Volumes of the bilateral hippocampal tail, left presubiculum_body, and right subiculum_body were significantly reduced in the T2DM dyslipidemia group compared to both the HC group and the T2DM normal lipidemia group. Post-hoc analyses revealed that the T2DM dyslipidemia group had the smallest hippocampal subfield volumes. Further subgroup analysis showed that T2DM dyslipidemia patients with MCI exhibited the most pronounced volume reductions in the bilateral hippocampal tail and right subiculum_body. After FDR correction, partial correlation analysis indicated that, in the T2DM dyslipidemia group, the left hippocampal tail volume was positively correlated with the Montreal Cognitive Assessment score. In the T2DM dyslipidemia without MCI group, the volume of the right subiculum_body was negatively correlated with fasting insulin levels and the insulin resistance index, but positively correlated with total cholesterol and low-density lipoprotein cholesterol levels. In T2DM patients with normal lipidemia without MCI, the volume of the right subiculum_body was positively correlated with TC levels. CONCLUSION T2DM patients with dyslipidemia, especially those with MCI, exhibit significant atrophy in hippocampal subfield volumes, with correlations observed between lipid levels and hippocampal subfield volume changes. These findings suggest that lipid alterations may play an essential role in hippocampal structural abnormalities and cognitive impairment in T2DM patients. This study provides new insights into the neuropathophysiological mechanisms underlying brain alterations and cognitive decline in T2DM.
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Affiliation(s)
- Chen Yang
- Department of Radiology, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Huiyan Zhang
- School of Clinical Medicine, Ningxia Medical University, Yinchuan 750000, China
| | - Jing Tian
- Department of Radiology, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Zhoule Li
- Department of Radiology, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Ruifang Liu
- Department of Radiology, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Gang Huang
- Department of Radiology, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Lianping Zhao
- Department of Radiology, Gansu Provincial Hospital, Lanzhou 730000, China.
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Yang H, Atak D, Yuan M, Li M, Altay O, Demirtas E, Peltek IB, Ulukan B, Yigit B, Sipahioglu T, Álvez MB, Meng L, Yüksel B, Turkez H, Kirimlioglu H, Saka B, Yurdaydin C, Akyildiz M, Dayangac M, Uhlen M, Boren J, Zhang C, Mardinoglu A, Zeybel M. Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies. Cell Rep Med 2025; 6:101935. [PMID: 39889710 PMCID: PMC11866494 DOI: 10.1016/j.xcrm.2025.101935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 09/20/2024] [Accepted: 01/08/2025] [Indexed: 02/03/2025]
Abstract
Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.
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Affiliation(s)
- Hong Yang
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Dila Atak
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye
| | - Meng Yuan
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Mengzhen Li
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Ozlem Altay
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Elif Demirtas
- School of Medicine, Koç University, Istanbul 34450, Turkiye
| | | | - Burge Ulukan
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye
| | - Buket Yigit
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye
| | - Tarik Sipahioglu
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye
| | - María Bueno Álvez
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Lingqi Meng
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | | | - Hasan Turkez
- Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkiye
| | - Hale Kirimlioglu
- Department of Pathology, School of Medicine, Acibadem Mehmet Ali Aydinlar University Istanbul 34752, Turkiye
| | - Burcu Saka
- Department of Pathology, School of Medicine, Koç University, Istanbul 34010, Turkiye
| | - Cihan Yurdaydin
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye
| | - Murat Akyildiz
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye
| | - Murat Dayangac
- Department of General Surgery, International School of Medicine, Medipol University, Istanbul 34010, Turkiye
| | - Mathias Uhlen
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Jan Boren
- Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Cheng Zhang
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden
| | - Adil Mardinoglu
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden; Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK.
| | - Mujdat Zeybel
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, İstanbul 34010, Turkiye; Clinical Trials Unit, Koç University Hospital, Istanbul 34010, Turkiye.
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30
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Liu Z, Jiang Y, Suo C, Yuan H, Yuan Z, Zhang T, Jin L, Chen X. Cohort Profile: Taizhou Study of Liver Diseases (T-SOLID). Int J Epidemiol 2025; 54:dyaf030. [PMID: 40199566 DOI: 10.1093/ije/dyaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 03/07/2025] [Indexed: 04/10/2025] Open
Affiliation(s)
- Zhenqiu Liu
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Huangbo Yuan
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Ziyu Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Li Jin
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
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Thangaraj SV, Bellingham M, Lea R, Evans N, Sinclair K, Padmanabhan V. Developmental programming: Sex-specific effects of prenatal exposure to a real-life mixture of environmental chemicals on liver function and transcriptome in sheep. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 367:125630. [PMID: 39756566 PMCID: PMC11813678 DOI: 10.1016/j.envpol.2025.125630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 12/01/2024] [Accepted: 01/01/2025] [Indexed: 01/07/2025]
Abstract
Humans are chronically exposed to a mixture of environmental chemicals (ECs), many with metabolic and endocrine disrupting potential, contributing to non-communicable disease burden. Understanding the effects of chronic exposure to low-level mixtures of ECs requires an animal model that reflects real-world conditions, lags behind studies on single ECs. Biosolids, from wastewater treatment, offers a real-life model to investigate the developmental health risks from EC mixtures. Prenatal biosolids exposure studies have documented metabolic perturbations including heavier thyroid glands in male fetuses and reduced bodyweight in prepubertal male lambs followed by catchup growth. We hypothesized that maternal preconceptional and gestational exposure of sheep to biosolids programs sex-specific transcriptional and functional changes in the offspring liver. Ewes (F0) were grazed on either inorganic fertilizer (C) or biosolids-treated pastures (BTP) preconception till parturition. All lambs (n = 15/group with male n = 7/group and females n = 8/group) were raised on Control pastures until euthanasia at 9.5 weeks. Next generation sequencing of liver RNA and DESeq2 was used to identify exposure-specific differentially expressed genes (DEG) and sex-differentially expressed genes (SDG). Liver function was assessed with markers of oxidative stress, triglyceride and fibrosis markers. Control lambs exhibited 647 SDGs confirming the inherent sexual dimorphism in hepatic gene expression. A sex-stratified analysis identified 10 DEG, mostly affecting metabolism, in male and none in female lambs. Biosolids exposure diminished the sexual dimorphism in hepatic gene expression barring 41 genes, potentially due to the increase in androgenic steroids found in F0 maternal circulation. Additionally, BTP male lambs showed elevated plasma triglyceride and a trend towards increased liver triglyceride concentrations. The identified effects of prenatal exposure to low-dose mixture of ECs via biosolids, in a precocial species paralleling human developmental patterns holds translational importance for understanding the sexually dimorphic origin of non-communicable diseases.
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Affiliation(s)
| | - Michelle Bellingham
- School of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK
| | - Richard Lea
- Schools of Biosciences and Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, UK
| | - Neil Evans
- School of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK
| | - Kevin Sinclair
- Schools of Biosciences and Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, UK
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Song J, Gao Z, Lai L, Zhang J, Liu B, Sang Y, Chen S, Qi J, Zhang Y, Kai H, Ye W. Machine learning-based plasma metabolomics for improved cirrhosis risk stratification. BMC Gastroenterol 2025; 25:61. [PMID: 39915740 PMCID: PMC11800577 DOI: 10.1186/s12876-025-03655-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 01/29/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND Cirrhosis is a leading cause of mortality in patients with chronic liver disease (CLD). The rapid development of metabolomic technologies has enabled the capture of metabolic changes related to the progression of cirrhosis. METHODS This study used proton nuclear magnetic resonance (1 H-NMR) serum metabolomics data from the UK Biobank (UKB) and employed elastic net-regularized Cox proportional hazards models to explore the role of metabolomics in cirrhosis risk stratification in patients with CLD. Metabolomic data were integrated with aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 score (FIB-4) to construct predictive models for cirrhosis risk. The model performance was assessed in both the derivation and validation cohorts. RESULTS A total of 2,738 eligible patients were included in the analysis. Several metabolites showed an independent association with cirrhosis events (68 out of 168 metabolites after adjustment for age and sex, and 21 out of 168 metabolites after full adjustment). The integration of metabolomics with FIB-4 improved the predictive performance compared to FIB-4 alone (Harrell's C: 0.717 vs. 0.696, ΔC = 0.021, 95% confidence interval [CI] 0.014-0.028, Net Reclassification Improvement [NRI]: 0.504 [0.488-0.520]). Similarly, the combination of metabolomics with APRI also improved predictive performance compared to APRI alone (Harrell's C: 0.747 vs. 0.718, ΔC = 0.029, 95% CI 0.022-0.035, NRI: 0.378 [0.366-0.389]). Key metabolites, including branched-chain amino acids (BCAAs), lipids, and markers of oxidative stress, were identified as significant predictors. Pathway enrichment analysis revealed that disruptions in lipid and amino acid metabolism play a central role in the progression of cirrhosis. CONCLUSION 1 H-NMR serum metabolomics significantly improves the prediction of cirrhosis risk in patients with CLD. The APRI + Metabolomics model demonstrated strong discriminatory power, with key metabolites involved in fatty acid and amino acid metabolism, providing a promising tool for the early screening of cirrhosis risk.
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Affiliation(s)
- Jingru Song
- Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Ziwei Gao
- Hangzhou School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Liqun Lai
- Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Jie Zhang
- Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Binbin Liu
- Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Yi Sang
- Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Siqi Chen
- Hangzhou School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Jiachen Qi
- Hangzhou School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Yujun Zhang
- Hangzhou School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China
| | - Huang Kai
- Department of cardiovascular surgery, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
| | - Wei Ye
- Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, Zhejiang, China.
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Gan C, Yuan Y, Shen H, Gao J, Kong X, Che Z, Guo Y, Wang H, Dong E, Xiao J. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Ther 2025; 10:33. [PMID: 39904973 PMCID: PMC11794951 DOI: 10.1038/s41392-024-02072-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 10/06/2024] [Accepted: 11/12/2024] [Indexed: 02/06/2025] Open
Abstract
As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.
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Affiliation(s)
- Can Gan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Aier Institute of Ophthalmology, Central South University, Changsha, China
| | - Haiyuan Shen
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Jinhang Gao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangxin Kong
- Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, China
| | - Zhaodi Che
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yangkun Guo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Erdan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Jia Xiao
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
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Liu X, Huang X, Zhang M, Jiang T, Zhang G. Letter: A Prospective Study on the Prevalence of MASLD in Patients With Type 2 Diabetes and Hyperferritinaemia. Aliment Pharmacol Ther 2025. [PMID: 39905793 DOI: 10.1111/apt.18419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 11/18/2024] [Accepted: 11/18/2024] [Indexed: 02/06/2025]
Affiliation(s)
- Xiaojuan Liu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, China
- Traditional Chinese Medicine "Preventing Disease" Wisdom Health Project Research Center of Zhejiang, Hangzhou, China
| | - Xueru Huang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, China
- Traditional Chinese Medicine "Preventing Disease" Wisdom Health Project Research Center of Zhejiang, Hangzhou, China
| | - Mingsi Zhang
- Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, China
| | - Tao Jiang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, China
- Traditional Chinese Medicine "Preventing Disease" Wisdom Health Project Research Center of Zhejiang, Hangzhou, China
| | - Guangji Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou, China
- Traditional Chinese Medicine "Preventing Disease" Wisdom Health Project Research Center of Zhejiang, Hangzhou, China
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Wu M, Li K, Wu J, Ding X, Ma X, Wang W, Xiao W. Ginsenoside Rg1: A bioactive therapeutic agent for diverse liver diseases. Pharmacol Res 2025; 212:107571. [PMID: 39756553 DOI: 10.1016/j.phrs.2024.107571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 12/10/2024] [Accepted: 12/29/2024] [Indexed: 01/07/2025]
Abstract
Diverse liver diseases are characterised by late diagnosis and rapid progression and have become one of the major threats to human health. To delay the transition from benign tissue lesions to a substantial organ injury, scientists have gradually applied natural compounds derived from plants as a complementary therapy in the field of hepatology. Ginseng (Panax ginseng C. A. Meyer) is a tonic traditional Chinese herbal medicine, and natural products, including ginsenoside Rg1 (G-Rg1), which is a kind of 20(S)-protopanaxatriol saponin with a relatively high biological activity, can be isolated from the roots or stems of ginseng. Given these information, this review aimed to summarise and discuss the metabolic mechanisms of G-Rg1 in the regulation of diverse liver diseases and the measures to improve its bioavailability. As a kind of monomer in Chinese medicine with multitarget pharmacological effects, G-Rg1 can provide significant therapeutic benefits in the alleviation of alcoholic liver disease, nonalcoholic fatty liver disease, liver fibrosis, viral hepatitis, etc., which mainly rely on the inhibition of apoptosis, strengthening endogenous anti-inflammatory and antioxidant mechanisms, activation of immune responses and regulation of efflux transport signals, to improve pathological changes in the liver caused by lipid deposition, inflammation, oxidative stress, accumulation of hepatotoxic product, etc. However, the poor bioavailability of G-Rg1 must be overcome to improve its clinical application value. In summary, focusing on the hepatoprotective benefits of G-Rg1 will provide new insights into the development of natural Chinese medicine resources and their pharmaceutical products to target the treatment of liver diseases.
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Affiliation(s)
- Mingyu Wu
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Ke Li
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Jiabin Wu
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Xianyi Ding
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Xiaotong Ma
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Wenhong Wang
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; Biomedical Research Institute, Hunan University of Medicine, Huaihua 418000, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Weihua Xiao
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
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Lu Z, Meng C, Yang J, Wang X, Li X, Zhang J, Tian X, Wang Q. Effect of different intensity aerobic exercise on remodeling immune microenvironment of adipose tissue in obesity mouse. Am J Physiol Regul Integr Comp Physiol 2025; 328:R220-R234. [PMID: 39745717 DOI: 10.1152/ajpregu.00227.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/06/2024] [Accepted: 12/10/2024] [Indexed: 01/26/2025]
Abstract
Obesity can change the immune microenvironment of adipose tissue and induce inflammation. This study is dedicated to exploring the internal mechanism by which different intensities of exercise reprogram the immune microenvironment of epididymal adipose tissue in nutritionally obese mice. C57BL/6J male obese mouse models were constructed by high-fat diet, which were respectively obese control group (OC), moderate-intensity continuous exercise group (HF-M), high-intensity continuous exercise group (HF-H), and high-intensity intermittent exercise group (HF-T). The exercise group was subjected to aerobic exercise intervention for 8 wk, and samples of mice were collected at the fourth and eighth week, respectively. Mice blood, liver, and adipose tissue of the epididymis were collected for index detection and adipose tissue ordinary transcriptome sequencing. After exercise intervention, when compared with the OC group, the morphology and blood indexes of the exercise groups were significantly improved. The liver lipid content was decreased, adipose tissue inflammation was reduced, and the mRNA and protein expression levels of IL-1β, F4/80, and CD64 in adipose tissue were significantly decreased (P < 0.01). Among the three exercise groups, the effect of the HF-T group was more significant. When compared with the OC group, fibroblast-specific marker genes, neutrophil marker genes, macrophage marker genes, and immune-related signaling pathways were significantly downregulated in the HF-T group. Exercise can reshape the immune microenvironment of adipose tissue, and high-intensity intermittent aerobic exercise is the most effective.NEW & NOTEWORTHY The present study has revealed that obesity is capable of altering the immune microenvironment within adipose tissue, thereby giving rise to inflammation. It has been demonstrated that exercise holds the potential to reverse the onset of inflammatory responses, with high-intensity intermittent aerobic exercise emerging as the most efficacious approach.
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Affiliation(s)
- Zhimin Lu
- College of Management, Qilu Medical University, Zibo, People's Republic of China
- College of Sport and Health, Shandong Sport University, Jinan, People's Republic of China
| | - Chang Meng
- College of Management, Qilu Medical University, Zibo, People's Republic of China
| | - JinRu Yang
- College of Management, Qilu Medical University, Zibo, People's Republic of China
| | - Xuecong Wang
- College of Management, Qilu Medical University, Zibo, People's Republic of China
| | - Xueying Li
- College of Management, Qilu Medical University, Zibo, People's Republic of China
| | - Jie Zhang
- College of Medical Laboratory, Qilu Medical University, Zibo, People's Republic of China
| | - Xuewen Tian
- College of Sport and Health, Shandong Sport University, Jinan, People's Republic of China
| | - Qinglu Wang
- College of Sport and Health, Shandong Sport University, Jinan, People's Republic of China
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Zheng Y, Sun Y, Ren W, Duan R, Li S, Chen M, Qin H, Ying M, Ren J. Factors Associated with Nonalcoholic Fatty Liver Disease in a Non-Overweight/Obese and Overweight/Obese Chinese Population at Risk for Metabolic Syndrome: A Cross-Sectional Multicenter Study. Metab Syndr Relat Disord 2025; 23:41-52. [PMID: 39311687 DOI: 10.1089/met.2024.0168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025] Open
Abstract
Background: To investigate the association of demographic, clinical, and metabolic factors with nonalcoholic fatty liver disease (NAFLD) in a non-overweight/obese and overweight/obese Chinese population at risk for metabolic syndrome. Patients and Method: A cross-sectional multicenter study was conducted using convenience sampling from eight selected counties/cities in Zhejiang, China, between May 2021 and September 2022. Demographics, epidemiological, anthropometric, and clinical characteristics were obtained from a questionnaire. Least absolute shrinkage and selection operator (LASSO)-logistic regression analysis was used to identify the variables associated with NAFLD. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value and clinical utility of the variables and models. Results: A total of 1739 patients were enrolled in the final analysis, 345 (19.8%) were non-overweight/obese and 1394 (80.2%) were overweight/obese participants. There were 114 (33.0%) and 1094 (78.5%) patients who met the criteria for NAFLD in the non-overweight/obese participants and the overweight/obese participants respectively. Older age, current smoking, higher triglyceride (TG) levels, higher AST levels, higher albumin levels, lower insulin levels, and higher controlled attenuation parameter (CAP) scores were associated with NAFLD in both non-overweight/obese and overweight/obese participants. The combination of TG+CAP scores had strong predictive values for NAFLD, especially in non-overweight/obese (Area Under Curve = 0.812, 95% confidence interval: 0.764-0.863). DCA showed a superior net benefit of the TG+CAP score over other variables or models, suggesting a better clinical utility in identifying NAFLD. Conclusions: More stringent lipid management strategies remain essential, and the convenience and efficacy of transient elastography for liver steatosis should be recognized, especially in the non-overweight/obese population.
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Affiliation(s)
- Yang Zheng
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Allergy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yujing Sun
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wen Ren
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ruoshu Duan
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shuai Li
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Mingmin Chen
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hongli Qin
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Meike Ying
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jingjing Ren
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Hu B, Yang L, Li RB, Gong J, Dai EH, Wang W, Lin FQ, Wang CM, Yang XL, Han Y, Qi XL, Teng J, Wang YJ, Wang CB. A nomogram model for predicting advanced liver fibrosis in patients with hepatitis B: A multicenter study. Clin Chim Acta 2025; 567:120102. [PMID: 39694219 DOI: 10.1016/j.cca.2024.120102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND Biopsy is the gold standard method for diagnosing liver fibrosis. FibroScan is a non-invasive method of diagnosing liver fibrosis, but it still faces some limitations. This study aimed to establish a nomogram model and identify patients at high risk of advanced liver fibrosis associated with hepatitis B infection. METHODS Data were collected from 375 patients with hepatitis B who underwent liver biopsy. Patients were divided randomly into the training (n = 263) and validation sets (n = 112). Their demographic and clinical characteristics were analyzed using the least absolute shrinkage and selection operator regression (LASSO). A nomogram model was established to predict the fibrosis stage, and its performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) and was compared with other recognized models. RESULTS In total, 209 patients with non-advanced fibrosis (S0-1) and 166 patients with advanced fibrosis (S ≥ 2) were included. Hyaluronic acid (HA), laminin, total cholesterol (TC), platelet, and age were entered into the nomogram model based on the LASSO analysis. The nomogram model for predicting advanced fibrosis exhibited a relatively high AUC in the training set. Compared with FIB4 and APRI, the nomogram model showed a better agreement between the actual status and predicted status based on the calibration curve. The nomogram model showed an AUC similar to FibroScan in the validation cohort, and showed high clinical net benefits in the training and validation sets. CONCLUSION Our nomogram model can help identify patients with hepatitis B and advanced liver fibrosis.
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Affiliation(s)
- Bo Hu
- Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Li Yang
- Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang 050024, China
| | - Rui-Bing Li
- Department of Laboratory Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jiao Gong
- Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Er-Hei Dai
- Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang 050024, China
| | - Wei Wang
- Clinical Laboratory, Fuyang People's Hospital, Fuyang 236011, China
| | - Fa-Quan Lin
- Department of Laboratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Chang-Min Wang
- Clinical Laboratory Center of People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Xiao-Li Yang
- Department of Clinical Laboratory, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Ying Han
- Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Long Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China
| | - Jing Teng
- Departments of Laboratory Medicine, Xiamen Traditional Chinese Medicine Hospital, Xiamen 361013, China.
| | - Ya-Jie Wang
- Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
| | - Cheng-Bin Wang
- Department of Laboratory Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
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Deng K, Li M, Xiang L, Wang Y, Li Y, Wen J, Li Y, Kuang S, Wen J, Zhou C, Huang S, Lv Z. Integrated UHPLC-Q-exactive orbitrap HRMS and serum pharmacochemistry for the investigation of anti-hepatic fibrosis effect of Baoganning Decoction. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 137:156363. [PMID: 39799893 DOI: 10.1016/j.phymed.2025.156363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/21/2024] [Accepted: 01/01/2025] [Indexed: 01/15/2025]
Abstract
BACKGROUND Early intervention in hepatic fibrosis (HF) is critical to reducing the risk of cirrhosis-related mortality and hepatocellular cancer. However, treating fibrosis has proven to be more challenging, with no approved anti-fibrotic therapies currently available for HF. Traditional Chinese medicines (TCMs) hold significant potential for the management of HF. PURPOSE This study aims to propose a systematic approach for investigating the pharmacological basis of Baoganning (BGN) Decoction, providing empirical evidence to support future research on its targets and mechanisms of BGN. STUDY DESIGN Ultrahigh-performance liquid chromatography coupled with high- resolution mass spectrometry (UPLC-HRMS) was employed to analyze the chemical composition of BGN. Key compounds were investigated using disease databases to predict relevant targets, followed by molecular docking and molecular dynamics simulations to explore molecular-level interactions. The efficacy and critical targets of BGN were validated through in vivo and in vitro experiments. METHODS UPLC-HRMS was used to identify the chemical composition of the BGN, and serum pharmacology determined the active chemical constituents in rat plasma. Zebrafish, HSC-T6 cells, JS-1 cell line and mice served as experimental models to evaluate the antifibrotic effects of BGN. RESULTS BGN demonstrated significant antifibrotic effect in vivo and in vitro models. A total of 757 compounds were identified in BGN, with 18 prototypical components and metabolites detected. Three compounds-quillaic acid, methyl cholate, and 3β-hydroxy-5-cholenoic exhibited dose-dependent inhibitory effects on HF. Molecular docking studies revealed stable interactions between these compounds and predicted targets. Additionally, the screened components effectively reduced the expression of α-SMA and COL-I in both a cellular model and a zebrafish fibrosis model in a dose-dependent manner. CONCLUSION The comprehensive analysis of BGN's chemical composition and its metabolic processes provides valuable insights into its pharmacological effects. These findings support the potential clinical and international application of BGN in treating hepatic fibrosis and improving patient outcomes.
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Affiliation(s)
- Kaili Deng
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Min Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Liangliang Xiang
- Auckland Bioengineering Institute, The University of Auckland, Auckland, 1010, New Zealand
| | - Yuhua Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Yamei Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Junya Wen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Yuanyuan Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Shanshan Kuang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Jinjie Wen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Chuying Zhou
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China
| | - Sha Huang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China.
| | - Zhiping Lv
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
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Serrano-Sandoval SN, Parralejo-Sanz S, Lobo MG, Cano MP, Antunes-Ricardo M. A bio-guided search of anti-steatotic compounds in Opuntia stricta var. dillenii by fast centrifugal partition chromatography. Food Chem 2025; 464:141682. [PMID: 39447270 DOI: 10.1016/j.foodchem.2024.141682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 09/27/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024]
Abstract
The fruit extract of Opuntia stricta var. dillenii (OSDE) has been recognized for its effects on hepatic steatosis, but the compounds responsible for this activity have yet to be precisely identified. This work aimed to evaluate the anti-steatotic effect of OSDE and its different fractions obtained by fast centrifugal-partition chromatography (FCPC) to identify the compounds potentially responsible for this biological activity. Hepatic lipid accumulation and triglyceride content were evaluated, as well as cellular antioxidant activity and inhibition of lipid peroxidation. Pool 1-Pool 4 showed lower lipid accumulation than OSDE in liver cells, while a greater reduction in triglyceride levels, even lower than OSDE and lovastatin (LOV), was observed for Pool 1, 9, and 10. Compared to OSDE, Pools 1,6, 7, and 12 showed higher cellular antioxidant effects, whereas OSDE showed better lipid peroxidation inhibition than all of Pools. Quinic and piscidic acids were the main bioactive present in Pool 1, exhibiting +1597 % and + 997 % increases in their content related to OSDE, respectively. Likewise, the most abundant compounds in Pool 2- Pool 4 were betalains such as betanin and isobetanin, with +163 % and + 162 % of increases in their concentration related to OSDE, respectively. Antioxidant effects in Pools 6 and 7 correlated with higher phenolic acid concentration. OSDE significantly reduced triglyceride levels in a steatotic-induced model. Although OSDE showed anti-steatotic effects, they were more pronounced for some of its constituents in FCPC Pools. Results suggested that these compounds might be potentially responsible for this anti-steatotic effect. FCPC fractionation facilitated the separate biological evaluation of OSDE constituents and thus identified them. Future studies should focus on validating these anti-steatotic effects in in vivo models.
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Affiliation(s)
- Sayra N Serrano-Sandoval
- Tecnologico de Monterrey, Centro de Biotecnología FEMSA, Escuela de Ingeniería y Ciencias, Av. Eugenio Garza Sada 2501 Sur, Monterrey, Nuevo Leon 64849, Mexico; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo Leon, Mexico.
| | - Sara Parralejo-Sanz
- Laboratory of Phytochemistry and Plant Food Functionality, Biotechnology and Food Microbiology Department, Institute of Food Science Research (CIAL) (CSIC-UAM), 28049 Madrid, Spain.
| | - M Gloria Lobo
- Departamento de Producción Vegetal en Zonas Tropicales y Subtropicales, Instituto Canario de Investigaciones Agrarias, 38270 Tenerife, Spain.
| | - M Pilar Cano
- Laboratory of Phytochemistry and Plant Food Functionality, Biotechnology and Food Microbiology Department, Institute of Food Science Research (CIAL) (CSIC-UAM), 28049 Madrid, Spain.
| | - Marilena Antunes-Ricardo
- Tecnologico de Monterrey, Centro de Biotecnología FEMSA, Escuela de Ingeniería y Ciencias, Av. Eugenio Garza Sada 2501 Sur, Monterrey, Nuevo Leon 64849, Mexico; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo Leon, Mexico.
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Wang J, Zhang Z, Yin S, Zhang S, Zhu L, Pan Y, Fan T, Cao F, Xiong Y, Jiang C, Wang G, Yang Y, Jia B, Liu J, Xia J, Yan X, Li J, Zhu C, Liu X, Chen Y, Wu C, Huang R. Favourable Prognosis of Patients With Untreated HBeAg-Negative Chronic Hepatitis B Virus Infection With HBsAg < 100 IU/mL. Aliment Pharmacol Ther 2025; 61:472-480. [PMID: 39523981 DOI: 10.1111/apt.18383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 06/12/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Serum hepatitis B surface antigen (HBsAg) < 100 IU/mL has been recently proposed as one of the key criteria of 'partial cure' in patients with chronic hepatitis B virus (HBV) infection. We analysed the clinical prognosis of hepatitis B e antigen (HBeAg)-negative untreated patients with HBsAg < 100 IU/mL and normal alanine aminotransferase (ALT) levels. METHODS Five hundred and twenty-one untreated patients with HBeAg negativity, HBsAg < 100 IU/mL and normal ALT levels were included from three hospitals. Spontaneous HBsAg seroclearance, phase transition, liver fibrosis progression and hepatocellular carcinoma (HCC) development were analysed. RESULTS The median age was 43.0 years, and 62.2% of the patients were male. After a median follow-up of 25.0 months, 52 (10.0%) patients achieved spontaneous HBsAg seroclearance. The annual HBsAg seroclearance rate is 4.2%. Patients with baseline HBsAg ≤ 10 IU/mL (adjusted hazard ratio [aHR] = 3.490, p < 0.001) and male sex (aHR = 1.980, p = 0.041) were more likely to achieve HBsAg seroclearance. Only 4 (0.8%) and 23 (4.8%) patients transitioned to the immune escape phase and HBeAg-negative indeterminate phase, respectively. Baseline serum HBsAg > 10 IU/mL (aHR = 3.846, p = 0.034) and detectable HBV DNA (aHR = 2.672, p = 0.023) were associated with transition to the HBeAg-negative indeterminate phase. No patient developed HCC or had fatal outcomes. CONCLUSIONS HBeAg-negative patients with serum HBsAg < 100 IU/mL and normal ALT levels had a favourable prognosis. HBsAg ≤ 10 IU/mL and male sex were associated with a higher rate of HBsAg seroclearance, while HBsAg > 10 IU/mL and detectable HBV DNA were associated with a higher risk of transition to the indeterminate phase.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Tao Fan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Fei Cao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ye Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu, China
| | - Guiyang Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yue Yang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Bei Jia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu, China
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Tian HY, Yu DJ, Xie T, Xu MX, Wang YH, Sun XL, Zhou XM, Han YX, Liao QQ, Zhao YJ, Liao J, El-Kassas M, Sun XD, Zhang YY. Cordycepin alleviates metabolic dysfunction-associated liver disease by restoring mitochondrial homeostasis and reducing oxidative stress via Parkin-mediated mitophagy. Biochem Pharmacol 2025; 232:116750. [PMID: 39793718 DOI: 10.1016/j.bcp.2025.116750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 12/01/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) keeps rising with only a few drugs available. The present study aims to investigate the effects and mechanisms of cordycepin on MASLD. Male C57BL/6 mice were induced with a 90-day high-fat diet (HFD) and intraperitoneal administration with streptozotocin to establish MASLD murine model. Then they were randomly divided into the HFD and cordycepin groups (15, 30, 45 mg/kg). Cordycepin was orally given for 30 days. Serum total cholesterol (TC), triacylglyceride (TG), and aspartate aminotransferase (AST) levels were measured. L02 cells were induced by oleate acid (OA) or lipopolysaccharides (LPS), and treated with cordycepin or combined with inhibitors including chloroquine, 3-Methyladenine, and compound C. Atg7 and Parkin were knocked down in L02 cells using siRNA. Oil Red O and Nile Red staining for measuring lipid deposition. Mitochondria were visualized by transfection with mCherry-TOMM20-N10. Quantitative real-time PCR, Western blotting, and immunofluorescence staining were used to determine expressions of key molecules in inflammation, lipid metabolism, mitochondria homeostasis, and oxidative stress. Cordycepin significantly mitigated lipid deposition and ballooning in the livers of MASLD mice. Serum TC, TG, and AST levels were decreased by cordycepin. Cordycepin alleviated OA-induced lipid deposition and LPS-induced inflammation in L02 cells, attenuated oxidative stress, promoted autophagy, and maintained the autophagic flux by activating AMP-activated protein kinase (AMPK). Cordycepin reduced the accumulation of impaired mitochondria by enhancing Parkin-dependent mitophagy and promoting mitochondrial biogenesis. Cordycepin alleviates MASLD by restoring mitochondrial homeostasis and reducing oxidative stress via activating the Parkin-mediated mitophagy.
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Affiliation(s)
- Hai-Ying Tian
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Dao-Jiang Yu
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China
| | - Teng Xie
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Meng-Xia Xu
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Yu-Hao Wang
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Xi-Lu Sun
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Xin-Meng Zhou
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Ying-Xuan Han
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Qing-Qing Liao
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Yu-Jie Zhao
- Medical College, Tibet University, Lhasa 850000, China
| | - Juan Liao
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Steatotic Liver Disease Study Foundation in Middle East and North Africa (SLMENA), Cairo, Egypt
| | - Xiao-Dong Sun
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; Medical College, Tibet University, Lhasa 850000, China.
| | - Yuan-Yuan Zhang
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China.
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Zhang X, Ji Z, He Q, Yang D, Wang X, Liu C, Zhang C, Yuan J, Xu N, Chu J. Gegen Qinlian Decoction inhibits liver ferroptosis in type 2 diabetes mellitus models by targeting Nrf2. JOURNAL OF ETHNOPHARMACOLOGY 2025; 340:119290. [PMID: 39732300 DOI: 10.1016/j.jep.2024.119290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 12/06/2024] [Accepted: 12/24/2024] [Indexed: 12/30/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Type 2 diabetes mellitus (T2DM) is a metabolic disease that can lead to complications affecting multiple organs, including the liver. Gegen Qinlian Decoction (GQD) has demonstrated considerable efficacy in the management of T2DM and its complications in accordance with the tenets of modern Chinese medicine. However, the molecular mechanism by which GQD alleviates diabetic liver injury is unclear. AIM OF THE STUDY To explore the effect and mechanism of GQD to ameliorate liver injury in T2DM. MATERIALS AND METHODS The active constituents of GQD were analyzed using UPLC. An in vivo T2DM mouse model was established by 6 weeks of high-fat diet and multiple streptozotocin (50 mg/kg/day) induction, followed by GQD administration. The evaluation of liver function, histopathology, oxidative stress, lipid peroxidation, and iron levels was conducted. In vitro experiments involved a high-glucose-induced AML12 cell model to assess oxidative stress, lipid peroxidation, and iron levels. RESULTS UPLC identified four main components in GQD: puerarin, baicalin, berberine and liquiritin. GQD administration resulted in enhanced liver function and a reduction in injury, accompanied by elevated antioxidant enzyme activity, increased GPX4 expression and diminished reactive oxygen species in T2DM mice. GQD treatment reduced lipid peroxidation and regulated iron transport proteins, thereby alleviating iron overload. In AML12 cells, GQD administration resulted in regulated mitochondrial morphology. CONCLUSION Our findings demonstrated that GQD ameliorated liver injury in T2DM by inhibiting ferroptosis through the modulation of Nrf2.
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Affiliation(s)
- Xinyu Zhang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Zhangxin Ji
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Qing He
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Dongmei Yang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Xueyang Wang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Conghui Liu
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Chuanqi Zhang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; School of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China
| | - Jingjing Yuan
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China.
| | - Na Xu
- College of Food and Nutrition, Joint Research Center for Food Nutrition and Health of IHM, Anhui Agricultural University, Hefei, Anhui, 230036, PR China; Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization of Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Food and Nutrition, Anhui Agricultural University, Hefei, Anhui, 230036, PR China.
| | - Jun Chu
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China; Institute of Surgery, Anhui Academy of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, PR China.
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Sun Y, Hu D, Yu M, Liang SB, Zheng Y, Wang X, Tong G. Diagnostic Accuracy of Non-Invasive Diagnostic Tests for Nonalcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis. Clin Epidemiol 2025; 17:53-71. [PMID: 39897720 PMCID: PMC11786599 DOI: 10.2147/clep.s501445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 01/17/2025] [Indexed: 02/04/2025] Open
Abstract
PURPOSE In recent decades, numerous non-invasive tests (NITs) for diagnosing nonalcoholic fatty liver disease (NAFLD) have been developed, however, a comprehensive comparison of their relative diagnostic accuracies is lacking. We aimed to assess and compare the diagnostic accuracy of various NITs for NAFLD using network meta-analysis (NMA). MATERIALS AND METHODS We conducted a systematic search in seven databases up to April 2024 to identify studies evaluating the diagnostic values of NITs, with liver biopsy as the gold standard. The participants included patients with suspected or confirmed NAFLD, irrespective of age, sex, ethnicity. Statistical analysis was conducted using R 4.0.3 for Bayesian NMA and STATA 17.0 for pairwise meta-analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUC), and superiority index were calculated. Bayesian calculations were performed using the Rstan package, specifying parameters like MCMC chain count, iteration count, and operational cycles. The methodological quality of included studies was assessed using the QUADAS-2 tool. RESULTS Out of 15,877 studies, 180 were included in the quantitative synthesis, and 102 were used in head-to-head meta-analyses. For diagnosing steatosis stage 1, Hydrogen Magnetic Resonance Spectroscopy (H-MRS, DOR 15,745,657.6, 95% CI 17.2-1,014,063.59) proved to be the most accurate. For significant fibrosis, HRI leading (DOR 80.94, 95% CI 6.46-391.41), For advanced fibrosis, CK-18 showed the highest performance (DOR 102654.16, 95% CI 1.6-134,059.8). For high-risk NASH, Real-Time Elastography showing the highest performance (DOR 18.1, 95% CI 0.7-96.33). Meta-regression analyses suggested that variability in the diagnostic accuracy of NITs for NAFLD may result from differences in study design, thresholds, populations, and performance indicators. CONCLUSION We conducted a network meta-analysis to rank the accuracy of these tests. While some results are promising, not all NITs demonstrate substantial accuracy, highlighting the need for validation with larger datasets. Future research should concentrate on studying the thresholds of NITs and enhancing the clarity of methodological reporting.
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Affiliation(s)
- Yuxin Sun
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
| | - Die Hu
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
| | - Mingkun Yu
- Department of Oncology, Binzhou Hospital of Traditional Chinese Medicine, Binzhou, People’s Republic of China
| | - Shi-Bing Liang
- Clinical Study Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
- Centre for Evidence-Based Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
- Postdoctoral Research Station, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Youyou Zheng
- Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
| | - Xin Wang
- Department of Traditional Chinese Medicine, Sanbo Brian Hospital of Capital Medical University, Beijing, People’s Republic of China
| | - Guangdong Tong
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
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Tao Y, Niu Q, Yao Y, Wang K, Dong H, Zhao X, Zeng Z, Li H. Qizhu Rougan Granules suppress liver fibrosis by inhibiting the expression of the P2Y14 receptor on hepatic stellate cells. Front Pharmacol 2025; 15:1528100. [PMID: 39850561 PMCID: PMC11755101 DOI: 10.3389/fphar.2024.1528100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 12/19/2024] [Indexed: 01/25/2025] Open
Abstract
Introduction Liver fibrosis is a globally prevalent chronic liver disease, often representing the advanced stage of various chronic liver conditions. Despite its widespread occurrence, there is currently no widely accepted or effective treatment for liver fibrosis. However, increasing evidence supports the efficacy of Traditional Chinese Medicine (TCM) in inhibiting the progression of fibrosis. In this study, we explored the effects and potential mechanisms of Qizhu-Ruogan-Granules (QZRG), a formulation from the Affiliated Hospital of the Chengdu University of TCM, on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Methods A total of 40 male C57BL/6J mice were randomly divided into five groups (n = 8 per group), with liver fibrosis induced by injecting 10% CCl4 for 15 weeks. From the 7th week onward, QZRG granules were administered orally to the treatment groups at low, medium, and high doses. To assess liver function, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Liver morphology and fibrosis were evaluated using hematoxylin-eosin (H&E) and Masson's trichrome staining, while gene and protein expression levels were analyzed through quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot techniques. Results The results showed that QZRG granules significantly reduced serum levels of AST, ALT, and ALP in CCl4-treated mice, alleviated liver damage, and reduced collagen accumulation. Furthermore, QZRG granules inhibited the expression of apoptosis-related proteins BAX, Caspase9, Caspase8, and Caspase3, while reducing P2Y14 expression in fibrotic liver tissues. Additionally, QZRG granules suppressed the proliferation of activated hepatic stellate cells. Conclusion Our findings suggest that QZRG granules may exert anti-fibrotic effects by downregulating P2Y14 expression and effectively slowing the progression of liver fibrosis.
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Affiliation(s)
- Yujing Tao
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qun Niu
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yuanqian Yao
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Kaixin Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Haijian Dong
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xin Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Zijian Zeng
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Hui Li
- Hospital of Chengdu University of Traditional Chinese Medicine, TCM Hospital of Sichuan Province, Chengdu, Sichuan, China
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Liu S, Wan H, Yang L, Shen J, Qi X. High prevalence of steatotic liver disease and fibrosis in the general population: A large prospective study in China. J Hepatol 2025; 82:e23-e25. [PMID: 39084473 DOI: 10.1016/j.jhep.2024.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/02/2024]
Affiliation(s)
- Shanghao Liu
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China; Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Heng Wan
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Guangdong, China
| | - Ling Yang
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
| | - Jie Shen
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Guangdong, China.
| | - Xiaolong Qi
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China; Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China.
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Zong J, Li Y, Zhou W, Mao M, Xu X, Cai S, Li M, Ding K. The structure elucidation and alleviating effect on liver fibrosis in vivo of a pectin-like polysaccharide isolated from Buddleja officinalis. Int J Biol Macromol 2025; 284:137936. [PMID: 39579817 DOI: 10.1016/j.ijbiomac.2024.137936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 11/08/2024] [Accepted: 11/20/2024] [Indexed: 11/25/2024]
Abstract
Buddleja officinalis has been used as a traditional Chinese medicine for years. Although evidence has demonstrated it can enhance liver function, the active material basis remains unknown. We hypothesize polysaccharides from Buddleja officinalis may be the active material against liver disease. Herein, we elucidated the structure of a novel pectin-like polysaccharide designed BOM0.05S2 with a molecular weight of 13.6 kDa. Combined with endo-1, 4-β-Mannanase degradation, we found its backbone consists of alternate 1, 2, 4-linked α-Rhap and 1, 4-linked α-GalpA (RG-I type pectin) and mannoglucan, with branches of 1, 4-, 1, 6- and 1, 3, 6-linked β-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf, T-linked β-Manp and T-linked α-Glcp substituted at C-4 of 1, 2, 4-linked α-Rhap and C-6 of 1, 4, 6-linked α-Glcp. As speculated, BOM0.05S2 showed a significant improvement on carbon tetrachloride (CCl4)-induced liver damage in mice. Bioactivity test showed that BOM0.05S2 reduced AST, ALT and four indexes of liver fibrosis including LN, HA, IV-C, PC-III. Further, we demonstrated that BOM0.05S2 attenuated the collagenous fiber and α-SMA in liver. These findings highlight the potential of BOM0.05S2 as a lead compound for the treatment of liver fibrosis.
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Affiliation(s)
- Jianing Zong
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province 210029, China
| | - Yun Li
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
| | - Wanqi Zhou
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China; Lingang Laboratory, Shanghai, China
| | - Mengfei Mao
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
| | - Xin Xu
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
| | - Simin Cai
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, Henan University, Kaifeng, Henan Province 475004, China
| | - Meixia Li
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
| | - Kan Ding
- Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province 210029, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Science, SSIP Healthcare and Medicine Demonstration Zone, Zhongshan Tsuihang New District, Zhongshan 528400, China; School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China; Lingang Laboratory, Shanghai, China.
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Yu H, Su X, Tao W, Sun W, Zhang X, Han Q, Zhao Z, Zhang Y, Chen X, Liu X, Jia D, Fang L, Li L. Prevalence and characteristics of liver steatosis and fibrosis in type 2 diabetes mellitus (T2DM) patients: a cross-sectional study in populations of eastern China. BMJ Open 2024; 14:e087550. [PMID: 39672583 PMCID: PMC11647396 DOI: 10.1136/bmjopen-2024-087550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 11/22/2024] [Indexed: 12/15/2024] Open
Abstract
OBJECTIVES To describe the prevalence, clinical characteristics and risk factors of liver steatosis and fibrosis in type 2 diabetes mellitus (T2DM) patients in eastern China. DESIGN A cross-sectional, multicentre study based on an ongoing cohort study. SETTING 16 clinics in eastern China, including primary clinics to tertiary hospitals. PARTICIPANTS 1816 patients with T2DM diagnosis who met the inclusion criteria were recruited into the study. INTERVENTION Participants underwent elastography examination. MAIN OUTCOME MEASURES Descriptive analysis was performed to calculate the prevalence and characteristics of liver steatosis and fibrosis. The correlated factors were analysed using single- and multivariate logistic regression analysis. RESULTS The prevalence of liver steatosis in T2DM patients is 69.7%, with 46% moderate to severe steatosis. 34.6% and 6.7% of the patients were detected with liver fibrosis and cirrhosis. Steatosis patients were younger, had higher body mass index (BMI), higher levels of insulin resistance and more severe lipid metabolism disorders. Similar trends of differences were observed in patients with fibrosis. Female gender (OR=0.574, 95% CI 0.381 to 0.865), BMI (OR=1.491, 95% CI 1.375 to 1.616), disease duration, inflammation and serum lipid profile markers were risk factors of steatosis, while BMI (OR=1.204, 95% CI 1.137 to 1.275) and female gender (OR=0.672, 95% CI 0.470 to 0.961) were still the most significant predictors of liver fibrosis. CONCLUSIONS The prevalence of liver steatosis and fibrosis were high in patients with T2DM. Liver steatosis and fibrosis in these patients appeared to be more associated with lipid metabolism disorders and insulin resistance rather than glucose levels. TRIAL REGISTRATION NUMBER Clinical trial: NCT05597709.
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Affiliation(s)
- Hekai Yu
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Xianghui Su
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, Xinjiang, China
| | - Wenxuan Tao
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Weixia Sun
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Xiaoyan Zhang
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
| | - Qing Han
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
| | - Zhuoxiao Zhao
- Nanjing Gaochun Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Yan Zhang
- Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xiaoqian Chen
- Department of Endocrinology, Nanjing Central Hospital, Nanjing, Jiangsu, China
| | - Xinliang Liu
- Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China
| | - Dianrong Jia
- Department of Endocrinology, Taizhou Jiangyan Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu, China
| | - Li Fang
- Nanjing Gaochun Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Ling Li
- Department of Endocrinology, School of Medicine, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
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Ding D, Hu Y, Jia G, Wang B, Zheng L, Deng J, Sun R, Wang X, Guo G, Cui L, Shang Y, Han Y. Low-risk individuals with primary biliary cholangitis and significant liver stiffness: prognosis and treatment. Hepatol Int 2024:10.1007/s12072-024-10743-w. [PMID: 39661270 DOI: 10.1007/s12072-024-10743-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 10/26/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Some patients treated with ursodeoxycholic acid (UDCA) or combined fenofibrate had well-controlled biochemical parameters but high liver stiffness, and the prognosis as well as therapeutic options for these patients may be an area worthy of further exploration. AIMS To explore the prognosis and treatment of patients with low-risk and high liver stiffness. METHODS A retrospective study included 424 cases of UDCA monotherapy and 102 cases of combined fenofibrate treatment. RESULTS The combination of liver stiffness measurement (LSM) and the GLOBE score improved prognostic prediction for patients with UDCA monotherapy (area under the receiver operating characteristic curve [AUC] of 0.868 (0.811-0.925) for the fitted model and 0.834 (0.767-0.900) for the GLOBE score, p = 0.006). Further analyses revealed that LSM had an additive prognostic effect mainly in low-risk patients defined by GLOBE < 0.5 (AUC, 0.777 [0.724-0.825] vs 0.642 [0.583-0.699], p = 0.001). For patients in the low-risk group, the prognosis was worse when LSM > 11 kPa (7/53 [13%] vs 2/227 [1%], p = 0.001). The prognosis was consistent between patients in the "low-risk and LSM > 11 kPa" group and the medium-risk group defined by 0.5 < GLOBE < 1.8 (7/53 [13%] vs 22/121 [18%], p = 0.418). In low-risk patients treated with combined fenofibrate therapy, the prognosis was worse when LSM > 11 kPa (3/21 [14%] vs 0/47 [0%], p = 0.022). The prognosis was consistent between patients in the "low-risk and LSM > 11 kPa" and the medium-risk groups (3/21 [14%] vs 6/27 [22%], p = 0.353). Antifibrotic drugs failed to reduce the incidence of the primary outcome (5/45 [11%] vs 5/27 [19%], p = 0.598), and delayed the progression of LSM in patients with low-risk and LSM > 11 kPa at 36 months of follow-up (changes in LSM, - 3.31 [- 5.04 to - 1.52] vs - 1.74 [- 2.83 to 1.5], p = 0.046). CONCLUSIONS Patients with GLOBE-defined low-risk and LSM > 11 kPa had a poor prognosis, and antifibrotic therapy may slow the progression of liver stiffness in these patients.
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Affiliation(s)
- Dawei Ding
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Yinan Hu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Gui Jia
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Boling Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Linhua Zheng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Juan Deng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Ruiqing Sun
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Xiufang Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Guanya Guo
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Lina Cui
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Yulong Shang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Ying Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Air Force Military Medical University, Xi'an, 710032, Shaanxi, China.
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50
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Wang J, Zhu L, Zhang S, Zhang Z, Fan T, Cao F, Xiong Y, Pan Y, Li Y, Jiang C, Yin S, Tong X, Xiong Y, Xia J, Yan X, Liu Y, Liu X, Chen Y, Li J, Zhu C, Wu C, Huang R. Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA. Emerg Microbes Infect 2024; 13:2339944. [PMID: 38584592 PMCID: PMC11022914 DOI: 10.1080/22221751.2024.2339944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 04/03/2024] [Indexed: 04/09/2024]
Abstract
Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Tao Fan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Fei Cao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Ye Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Yuanyuan Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Chao Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Yali Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
| | - Yong Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, People’s Republic of China
| | - Yuxin Chen
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China
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