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Gui Z, Chen X, Wang D, Chen Z, Liu S, Yu G, Jiang Y, Duan H, Pan D, Lin X, Liu L, Wan H, Shen J. Inflammatory and metabolic markers mediate the association of hepatic steatosis and fibrosis with 10-year ASCVD risk. Ann Med 2025; 57:2486594. [PMID: 40189927 PMCID: PMC11980196 DOI: 10.1080/07853890.2025.2486594] [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: 12/02/2024] [Revised: 03/13/2025] [Accepted: 03/17/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND AND AIMS Liver steatosis and fibrosis increase the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk, though the roles of chronic inflammation and metabolic dysregulation remain unclear. This cross-sectional study quantitatively assesses this association and evaluates the mediating effects of metabolic dysregulation and chronic inflammation. METHODS In this study, we enrolled 6110 adults from ten communities in Canton, China. Hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE) through controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), while predicted 10-year ASCVD risk was calculated using the China-PAR project model. Associations between CAP/LSM values and predicted 10-year ASCVD risk were analyzed. Mediation analysis quantified the effects of high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), remnant cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C). The main statistical methods used included logistic regression, restricted cubic splines (RCS) analysis, interaction calculations, and mediation analysis to examine the relationships and mediators. RESULTS The study population had a mean age of 50.1 years (SD = 9.7), with 3927 females (64.3%) and 2183 males (35.7%). Additionally, 808 participants (13.2%) had type 2 diabetes, and 1911 participants (31.3%) had hypertension. Compared to the first CAP quartile (Q1), higher CAP quartiles showed increased odds ratios (OR) for predicted moderate to high 10-year ASCVD risk: 1.14 (0.89, 1.45), 1.37 (1.08, 1.73), and 2.44 (1.93, 3.10). Mediation analysis showed hs-CRP and HOMA-IR mediated CAP's link to ASCVD risk, with mediation proportions of 15.40% and 27.37%. RC and non-HDL-C mediated this association at 7.12% and 6.26%. Among patients with hepatic steatosis (CAP ≥ 248 dB/m), LSM Q4 participants had a significantly higher predicted 10-year ASCVD risk than those in LSM Q1 (OR 2.22, [1.52, 3.25]), with hs-CRP and HOMA-IR mediating 2.62% and 13.75%, respectively. CONCLUSION Liver steatosis and fibrosis were associated with the increased predicted ASCVD risk, with mediation effects from hs-CRP, HOMA-IR, RC, and non-HDL-C.
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Affiliation(s)
- Zihao Gui
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Xingying Chen
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Dongmei Wang
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Zhi Chen
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Siyang Liu
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Genfeng Yu
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Yuqi Jiang
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Hualin Duan
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Daoyan Pan
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China
| | - Xu Lin
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Lan Liu
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Heng Wan
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Jie Shen
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
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Dang M, Zhang J, Ren RX, Fu MM, Li KJ, Gao HQ, Zhang Q, Wang J, Sun J, Zhang XF, Wang CL, Zhang MM, Zhao CB. Platycodon grandiflorum Attenuates Non-Alcoholic Fatty Liver Disease in Rats Through Regulating Inflammatory Response via PPARγ and TLR4/NF-κB Signaling Pathway. Biomed Chromatogr 2025; 39:e70111. [PMID: 40395044 DOI: 10.1002/bmc.70111] [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: 04/02/2025] [Revised: 04/02/2025] [Accepted: 05/07/2025] [Indexed: 05/22/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been considered a main health concern worldwide, and Platycodon grandiflorum (PG) has been traditionally employed in ethnopharmacology for managing hepatic metabolic disorders. This study aimed to elucidate the potential effect of PG on NAFLD in rats, and furthermore, the mechanism was explored. PG supplementation significantly increased body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels in HFD-induced obese rats (p < 0.05). In addition, HFD-induced lipid accumulation and inflammatory response in the liver were also suppressed. Then, the factors contributing to the regulating effect of PG on NAFLD were estimated by using network pharmacology and RNA sequencing. Moreover, western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) suggested that PG treatment obviously downregulated the expression levels of nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), and inhibitor I kappa B alpha (IκBα), whereas it upregulated the expression of peroxisome proliferator-activated receptor-gamma (PPARγ). Taken together, these findings corroborated the modulatory capacity of PG on NAFLD rats through regulating inflammatory response via PPARγ and TLR4/NF-κB pathway.
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Affiliation(s)
- Ming Dang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Jie Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Run-Xin Ren
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Mao-Mao Fu
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Kang-Jie Li
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Huan-Qing Gao
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Qiao Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Jing Wang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Jing Sun
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
- Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xianyang, China
- Engineering Technology Research Center of Shaanxi Administration of Chinese Herbal Pieces, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Xiao-Fei Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Chang-Li Wang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Meng-Meng Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Chong-Bo Zhao
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China
- Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xianyang, China
- Engineering Technology Research Center of Shaanxi Administration of Chinese Herbal Pieces, Shaanxi University of Chinese Medicine, Xianyang, China
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Yang R, Jiang Q, Liu W, Wang F, Cao S. Serum polychlorinated biphenyls as a risk factor for MASLD: Exploring the association and underlying mechanisms. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 981:179617. [PMID: 40354702 DOI: 10.1016/j.scitotenv.2025.179617] [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: 02/16/2025] [Revised: 04/30/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND Fatty liver disease, a growing global health issue, is closely tied to metabolic disorders. The 2023 definition of metabolic-associated steatotic liver disease (MASLD) incorporates cardiometabolic risk factors, but the potential role of persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs), remains underexplored. Investigating the impact of environmental toxins on liver health is crucial for understanding emerging public health risks. METHODS 1080 participants were included from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). We employed weighted generalized linear models, weighted quantile sum regression, and Bayesian kernel machine regression to assess the relationship between serum PCB levels and MASLD, with NAFLD included for comparison. Protein interaction and enrichment analyses were also conducted to explore the underlying mechanisms. RESULTS PCB146, PCB156, PCB187, PCB174, and PCB180 were significantly associated with an increased MASLD risk in the GLM. Significant positive associations were found between serum PCB mixtures and MASLD in the WQS model (β: 0.411, p: 0.0056) and BKMR model (p < 0.05), with PCB180 contributing the most (β: 0.644, PIP: 0.903). NAFLD did not show significant associations. Network pharmacological analysis demonstrated enrichment in the regulation of lipolysis of adipocytes and the cAMP signaling pathway, and PPAR-γ and MAOA show significant importance in the protein-protein interaction networks. CONCLUSION This study underscores the epidemiological and mechanical link between MASLD and PCB exposure, highlighting the superiority of MASLD in identifying the impact of POPs on liver disease risk and particularly identifying PCB180 as a sentinel marker for PCB surveillance.
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Affiliation(s)
- Ruichen Yang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Qingqing Jiang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Wentao Liu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Furong Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Shiyi Cao
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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Ge Z, Wu Q, Lv C, He Q. The Roles of T Cells in the Development of Metabolic Dysfunction-Associated Steatohepatitis. Immunology 2025. [PMID: 40414629 DOI: 10.1111/imm.13943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 02/28/2025] [Accepted: 04/28/2025] [Indexed: 05/27/2025] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH), the progressed period of metabolic dysfunction-associated steatotic liver disease (MASLD), is a multifaceted liver disease characterised by inflammation and fibrosis that develops from simple steatosis, even contributing to hepatocellular carcinoma and death. MASH involves several immune cell-mediated inflammation and fibrosis, where T cells play a crucial role through the release of pro-inflammatory cytokines and pro-fibrotic factors. This review discusses the complex role of various T cell subsets in the pathogenesis of MASH and highlights the progress of ongoing clinical trials involving T cell-targeted MASH therapies.
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Affiliation(s)
- Zhifa Ge
- Department of General Surgery, Nanjing First Hospital, The Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qingwei Wu
- Department of General Surgery, Nanjing First Hospital, The Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chengyu Lv
- Department of General Surgery, Nanjing First Hospital, The Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qifeng He
- Department of General Surgery, Nanjing First Hospital, The Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Chen K, Feng Q, Liu H. Bibliometric visualization of hepatocellular carcinoma and metabolic syndrome research: trends and emerging areas. Discov Oncol 2025; 16:809. [PMID: 40388038 PMCID: PMC12089568 DOI: 10.1007/s12672-025-02518-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 04/28/2025] [Indexed: 05/20/2025] Open
Abstract
A growing body of research has highlighted the increasing relevance of hepatocellular carcinoma (HCC) and metabolic syndrome (MetS). However, a comprehensive bibliometric visualization analysis on this topic remains lacking. In this study, we retrieved 310 related articles from the Web of Science Core Collection, spanning from January 1, 2014, to December 31, 2023. Using VOS viewer and Cite Space software, we analyzed the relationships among authors, journals, institutions, countries, keywords, and citations. Between 2014 and 2023, there has been a steady increase in publications on HCC and MetS, with the United States and China being the leading contributors in terms of publication volume. The visualization analysis revealed that obesity, insulin resistance, MAFLD, and liver cirrhosis are emerging areas in the intersection of HCC and MetS. Additionally, the international community is increasingly adopting the disease diagnosis term MAFLD, which, compared to NAFLD, shows improved diagnostic performance for predicting both hepatic and extra-hepatic outcomes. Furthermore, hypertension and cardiovascular diseases are emerging as promising new research fields.
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Affiliation(s)
- Kang Chen
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou University, Chengguan District, Lanzhou, 730000, Gansu, China
| | - Qianye Feng
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
| | - Haipeng Liu
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou University, Chengguan District, Lanzhou, 730000, Gansu, China.
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Noon SL, Chun LF, Lam TBN, Thai NQN, Dunn W, Schwimmer JB. Prevalence and Predictors of Suspected Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents in the United States. Aliment Pharmacol Ther 2025; 61:1479-1488. [PMID: 39943715 PMCID: PMC11981549 DOI: 10.1111/apt.70022] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/20/2024] [Accepted: 02/01/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Nomenclature for steatotic liver disease has been updated to include metabolic dysfunction-associated steatotic liver disease (MASLD), which requires the presence of hepatic steatosis and at least one cardiometabolic risk factor. The prevalence of MASLD in adolescents is understudied. AIM To determine the prevalence of suspected MASLD among adolescents in the United States and to examine the relationships between elevated alanine aminotransferase (ALT) and cardiometabolic risk factors. METHODS A cross-sectional analysis of the National Health and Nutrition Examination Survey from 2011 to 2020 was conducted for adolescents aged 12-19 years. Elevated ALT was defined using sex-specific biological upper limits: > 26 U/L for males and > 22 U/L for females. Suspected MASLD was identified by elevated ALT and at least one cardiometabolic risk factor. Adolescents with elevated ALT were categorised as having suspected MASLD, elevated ALT due to other causes or cryptogenic ALT elevation. RESULTS Overall, 14.6% of adolescents had elevated ALT. Of these, 77.2% had suspected MASLD, 20.2% had cryptogenic ALT elevation, 1.9% took hepatotoxic medications and 0.7% had viral hepatitis. Body mass index had the strongest association with elevated ALT (OR 3.55), followed by high triglycerides (OR 2.09), low HDL cholesterol (OR 2.05) and high blood pressure (OR 1.93). CONCLUSIONS Most adolescents with elevated ALT met MASLD criteria, yet a portion lacked cardiometabolic risk factors or other identifiable causes. These results support the adoption of MASLD criteria in adolescents while indicating a need for further research into cryptogenic ALT elevation in paediatric populations.
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Affiliation(s)
- Sheila L. Noon
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsUniversity of California San Diego School of MedicineSan DiegoCaliforniaUSA
- University of California, San Diego School of MedicineSan DiegoCaliforniaUSA
| | - Lauren F. Chun
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsUniversity of California San Diego School of MedicineSan DiegoCaliforniaUSA
- Department of GastroenterologyRady Children's HospitalSan DiegoCaliforniaUSA
| | - Tin Bo Nicholas Lam
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsUniversity of California San Diego School of MedicineSan DiegoCaliforniaUSA
- Department of GastroenterologyRady Children's HospitalSan DiegoCaliforniaUSA
| | - Nhat Quang N. Thai
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsUniversity of California San Diego School of MedicineSan DiegoCaliforniaUSA
- University of California San Diego Herbert Wertheim School of Public Health and Human Longevity ScienceSan DiegoCaliforniaUSA
- San Diego State University School of Public HealthSan DiegoCaliforniaUSA
| | - Winston Dunn
- Department of GastroenterologyThe University of Kansas Health SystemKansas CityMissouriUSA
| | - Jeffrey B. Schwimmer
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsUniversity of California San Diego School of MedicineSan DiegoCaliforniaUSA
- Department of GastroenterologyRady Children's HospitalSan DiegoCaliforniaUSA
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Wu F, Zhang J, Sun W, Li JL, Zhang WQ, Bai M. Value of 1H-MRS abdominal fat quantification combined with serum IGF-1 in assessing severity of NAFLD in adolescents in Zhoushan Island area. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2025; 33:301-308. [DOI: https:/dx.doi.org/10.11569/wcjd.v33.i4.301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
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Wu F, Zhang J, Sun W, Li JL, Zhang WQ, Bai M. Value of 1H-MRS abdominal fat quantification combined with serum IGF-1 in assessing severity of NAFLD in adolescents in Zhoushan Island area. Shijie Huaren Xiaohua Zazhi 2025; 33:301-308. [DOI: 10.11569/wcjd.v33.i4.301] [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: 02/18/2025] [Revised: 04/11/2025] [Accepted: 04/22/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND The Zhoushan Island area, characterized by its unique living environment, has limited reported data on obesity and related metabolic disorders. In the era of personalized medical care, more refined diagnosis is critical for the treatment of patients' diseases. Despite China's extensive coastline, there is still a lack of relevant research exploring the combined use of 1H-magnetic resonance spectroscopy (1H-MRS) and insulin-like growth factor-1 (IGF-1) in the evaluation of non-alcoholic fatty liver disease (NAFLD) in adolescents.
AIM To explore the utility of quantitative 1H-MRS of adolescent abdominal fat combined with serum IGF-1 in evaluating the severity of NAFLD in adolescents from the Zhoushan Island area.
METHODS A total of 99 adolescent patients with suspected NAFLD who were admitted to Zhoushan Women's and Children's Hospital from January 2022 to June 2024 were selected. They were divided into a non-NAFLD group (41 cases), a mild NAFLD group (37 cases), and a moderate to severe NAFLD group (21 cases) according to pathological diagnosis. Metabolic-related indicators [body mass index (BMI), 2-hour postprandial glucose (2HPG), triglycerides (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] were compared among the three groups. The 1H-MRS spectral values, intrahepatic lipid (IHL), and serum IGF-1 were also compared among the three groups. The correlation between IHL, serum IGF-1, metabolic related indicators, and 1H-MRS spectral values was analyzed using Pearson correlation. The correlation between IHL, serum IGF-1, and disease severity was analyzed by point-biserial correlation. The value of IHL and serum IGF-1 for evaluating the severity of NAFLD was analyzed.
RESULTS In the moderate to severe NAFLD group, HDL-C levels were lower than those of the other two groups, while BMI, 2HPG, ALT, AST, TG, TC, and LDL-C levels were higher than those of the other two groups (P < 0.05). Compared to the non-NAFLD group and the mild NAFLD group, the moderate to severe NAFLD group had lower water peak values and higher lipid peak values (P < 0.05). The level of IHL in the moderate and severe NAFLD group was higher than those of the other two groups, while the level of IGF-1 was lower than those of the other two groups (P < 0.05). BMI, 2HPG, ALT, AST, TG, TC, and LDL-C were positively correlated with IHL and negatively correlated with IGF-1 (P < 0.05). HDL-C, water peak, and lipid peak were negatively correlated with IHL and positively correlated with IGF-1 (P < 0.05). The severity of NAFLD was positively correlated with IHL and negatively correlated with serum IGF-1 (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve (AUC) values of IHL and serum IGF-1 for evaluating the severity of NAFLD were 0.740 (95% confidence interval [CI]: 0.608-0.846) and 0.721 (95%CI: 0.588-0.831), respectively. The combined evaluation of the two had the highest AUC of 0.896 (95%CI: 0.787-0.961) (P < 0.05). High levels of IHL (> 18.51%) and low levels of serum IGF-1 (≤ 0.24 μg/L) can significantly distinguish the risk of developing moderate to severe NAFLD (P < 0.05).
CONCLUSION Abdominal fat quantified by 1H-MRS and serum IGF-1 are closely related to the metabolism of adolescents, and the combination of the two has high value for evaluaing the severity of NAFLD.
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Affiliation(s)
- Fan Wu
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Jie Zhang
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Wen Sun
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Jia-Lin Li
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Wen-Qi Zhang
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Min Bai
- Department of Pediatrics, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
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Wu F, Zhang J, Sun W, Li JL, Zhang WQ, Bai M. Value of 1H-MRS abdominal fat quantification combined with serum IGF-1 in assessing severity of NAFLD in adolescents in Zhoushan Island area. Shijie Huaren Xiaohua Zazhi 2025; 33:308-315. [DOI: 10.11569/wcjd.v33.i4.308] [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: 02/18/2025] [Revised: 04/11/2025] [Accepted: 04/22/2025] [Indexed: 04/28/2025] Open
Abstract
BACKGROUND The Zhoushan Island area, characterized by its unique living environment, has limited reported data on obesity and related metabolic disorders. In the era of personalized medical care, more refined diagnosis is critical for the treatment of patients' diseases. Despite China's extensive coastline, there is still a lack of relevant research exploring the combined use of 1H-magnetic resonance spectroscopy (1H-MRS) and insulin-like growth factor-1 (IGF-1) in the evaluation of non-alcoholic fatty liver disease (NAFLD) in adolescents.
AIM To explore the utility of quantitative 1H-MRS of adolescent abdominal fat combined with serum IGF-1 in evaluating the severity of NAFLD in adolescents from the Zhoushan Island area.
METHODS A total of 99 adolescent patients with suspected NAFLD who were admitted to Zhoushan Women's and Children's Hospital from January 2022 to June 2024 were selected. They were divided into a non-NAFLD group (41 cases), a mild NAFLD group (37 cases), and a moderate to severe NAFLD group (21 cases) according to pathological diagnosis. Metabolic-related indicators [body mass index (BMI), 2-hour postprandial glucose (2HPG), triglycerides (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] were compared among the three groups. The 1H-MRS spectral values, intrahepatic lipid (IHL), and serum IGF-1 were also compared among the three groups. The correlation between IHL, serum IGF-1, metabolic related indicators, and 1H-MRS spectral values was analyzed using Pearson correlation. The correlation between IHL, serum IGF-1, and disease severity was analyzed by point-biserial correlation. The value of IHL and serum IGF-1 for evaluating the severity of NAFLD was analyzed.
RESULTS In the moderate to severe NAFLD group, HDL-C levels were lower than those of the other two groups, while BMI, 2HPG, ALT, AST, TG, TC, and LDL-C levels were higher than those of the other two groups (P < 0.05). Compared to the non-NAFLD group and the mild NAFLD group, the moderate to severe NAFLD group had lower water peak values and higher lipid peak values (P < 0.05). The level of IHL in the moderate and severe NAFLD group was higher than those of the other two groups, while the level of IGF-1 was lower than those of the other two groups (P < 0.05). BMI, 2HPG, ALT, AST, TG, TC, and LDL-C were positively correlated with IHL and negatively correlated with IGF-1 (P < 0.05). HDL-C, water peak, and lipid peak were negatively correlated with IHL and positively correlated with IGF-1 (P < 0.05). The severity of NAFLD was positively correlated with IHL and negatively correlated with serum IGF-1 (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve (AUC) values of IHL and serum IGF-1 for evaluating the severity of NAFLD were 0.740 (95% confidence interval [CI]: 0.608-0.846) and 0.721 (95%CI: 0.588-0.831), respectively. The combined evaluation of the two had the highest AUC of 0.896 (95%CI: 0.787-0.961) (P < 0.05). High levels of IHL (> 18.51%) and low levels of serum IGF-1 (≤ 0.24 μg/L) can significantly distinguish the risk of developing moderate to severe NAFLD (P < 0.05).
CONCLUSION Abdominal fat quantified by 1H-MRS and serum IGF-1 are closely related to the metabolism of adolescents, and the combination of the two has high value for evaluaing the severity of NAFLD.
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Affiliation(s)
- Fan Wu
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Jie Zhang
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Wen Sun
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Jia-Lin Li
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Wen-Qi Zhang
- Department of Radiology, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
| | - Min Bai
- Department of Pediatrics, Zhoushan Women and Children's Hospital, Zhoushan 316000, Zhejiang Province, China
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Zhang K, Zhang S, Deng G, He G, Yuan Y, Fu Y, Liu Y, Gong Z, Kong L, Zheng C. Brown adipose tissue-derived extracellular vesicles regulate hepatocyte mitochondrial activity to alleviate high-fat diet-induced jawbone osteoporosis in mice. Front Endocrinol (Lausanne) 2025; 16:1583408. [PMID: 40343072 PMCID: PMC12058480 DOI: 10.3389/fendo.2025.1583408] [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: 02/25/2025] [Accepted: 03/25/2025] [Indexed: 05/11/2025] Open
Abstract
Background Lipid metabolic disorder (LMD) serves as a systemic driver of osteoporosis (OP), with jawbone osteoporosis (JOP) representing a clinically significant yet underexplored complication. Current clinical treatments for JOP remain suboptimal, highlighting the need for innovative approaches. The use of metabolic regulators represents a promising therapeutic strategy for OP management. While brown adipose tissue-derived extracellular vesicles (BEV) exhibit metabolic regulatory potential, their capacity to mitigate LMD-associated OP remains unclear. Methods A high-fat diet (HFD)-induced LMD mouse model was established to identify the JOP phenotype through micro-computed tomography (micro-CT) and transcriptomic profiling. BEV isolation was optimized using liberase enzyme-enhanced differential centrifugation, with in vivo tracking confirming biodistribution. In vitro, BEV effects on hepatocytes were assessed with triglyceride (TG) content, free fatty acid (FFA) levels, and mitochondrial function. The additional benefits of BEV on the osteogenic microenvironment were evaluated via AML12/MC3T3-E1 indirect co-culture under high-lipid conditions. Dual therapeutic effects of BEV on LMD and JOP in vivo were validated through metabolic phenotyping, micro-CT and histomorphometry analysis. Results Sixteen weeks of HFD successfully induced typical LMD and JOP manifestations in mice. Transcriptomic sequencing revealed downregulation of osteogenic-related genes concomitant with upregulation of lipid metabolism-associated genes in the jawbone of LMD mice. In vivo tracking showed the exogenous BEV predominantly accumulated in the liver rather than the jawbone. BEV treatment significantly reduced intracellular TG and FFA content in hepatocytes, while enhancing osteogenic activity of MC3T3-E1 cells through indirect co-culture. Mitochondrial analyses revealed that BEV effectively increased the proportion of active mitochondria, reduced reactive oxygen species (ROS) generation rate, and enhanced oxygen consumption rate (OCR) in hepatocytes. Biochemical assay and metabolic cage testing showed a lower systemic lipid content level along with improved fat utilization and thermogenesis capacity in BEV-treated mice. Micro-CT and immunofluorescence staining further confirm significant improvements in the jawbone of BEV-treated mice regarding bone volume fraction, trabecular number, trabecular thickness, trabecular separation, and RUNX2 expression. Conclusion This study establishes LMD as a crucial driver factor in JOP and identifies BEV-mediated mitochondrial transferring in hepatocytes as a therapeutic strategy for LMD-related JOP.
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Affiliation(s)
- Kai Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an, China
| | - Sha Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, China
- College of Basic Medicine, Shaanxi Key Laboratory of Research on TCM Physical Constitution and Diseases Prevention and Treatment, Shaanxi University of Chinese Medicine, Xianyang, China
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, China
| | - Guorong Deng
- Department of Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Guangxiang He
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, China
- The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Yuan Yuan
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, China
| | - Yu Fu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, China
| | - Yihan Liu
- Department of Stomatology, The First Medical Center, Chinese Chinese PLA General Hospital, Beijing, China
| | - Zhen Gong
- Analysis & Testing Laboratory for Life Sciences and Medicine of Fourth Military Medical University, Xi’an, China
| | - Liang Kong
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an, China
| | - Chenxi Zheng
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, China
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Jiang M, Butt AS, Cua IH, Pan Z, Al-Busafi SA, Méndez-Sánchez N, Eslam M. MAFLD vs. MASLD: a year in review. Expert Rev Endocrinol Metab 2025:1-12. [PMID: 40237514 DOI: 10.1080/17446651.2025.2492767] [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: 01/02/2025] [Accepted: 04/04/2025] [Indexed: 04/18/2025]
Abstract
INTRODUCTION In 2023, metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced following metabolic dysfunction-associated fatty liver disease (MAFLD). Both aim to address the limitations of nonalcoholic fatty liver disease (NAFLD). This review analyzes the similarities and differences between MAFLD and MASLD, focusing on their impacts on epidemiology, diagnosis, stigma, and related liver diseases. AREAS COVERED Current evidence suggests that MAFLD criteria effectively identify individuals at higher risk through a good balance of sensitivity and specificity. Moreover, MAFLD is a more generalizable term that is easily understood globally. EXPERT OPINION The transition from NAFLD to MAFLD and MASLD marks a significant advance in understanding fatty liver disease within hepatology. MAFLD identifies a homogeneous cohort of patients with fatty liver due to metabolic dysfunction and provides a valuable framework for holistic, patient-centered management strategies that consider various contributing factors to improve health outcomes.
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Affiliation(s)
- Mingqian Jiang
- Department of Endocrinology and Metabolism, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
| | - Amna Subhan Butt
- Section of Gastroenterology, Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Ian Homer Cua
- Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Taguig, Philippines
| | - Ziyan Pan
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
| | - Said A Al-Busafi
- Gastroenterology and Hepatology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
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12
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Suresh D, Gunaseelan B, Srinivas AN, Bharadwaj A, Joseph J, Megha, Varughese T, Satish S, Suvarna D, Santhekadur PK, Chidambaram SB, Duseja A, Kumar DP. Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems. Sci Rep 2025; 15:12088. [PMID: 40204999 PMCID: PMC11982280 DOI: 10.1038/s41598-025-96944-1] [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: 10/28/2024] [Accepted: 04/01/2025] [Indexed: 04/11/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated the mechanisms of how green jackfruit flour (JF) ameliorates metabolic-dysfunction-associated steatohepatitis (MASH) and halts the progression to hepatocellular carcinoma (HCC). The study used murine models of MASH and MASH-HCC that closely mimic human MASLD. C57Bl/6 male mice were fed with chow or western diet with normal or sugar water for 12 weeks, then randomized to receive either 5 kcal% green jackfruit flour (JF) or an equal volume of placebo flour (PB). JF significantly reduced body weight, liver injury, and insulin resistance, and alleviated obesity, steatosis, inflammation, fibrosis, and tumor development in WDSW or WDSW/CCl4 mice compared to placebo. Furthermore, JF activated AMPK (AMP-activated protein kinase) and inhibited MAPK (mitogen-activated protein kinase) signaling pathways in MASH and MASH-HCC models, respectively. Sodium propionate treatment, the primary short-chain fatty acid entering the liver from JF's soluble fiber microbial fermentation, further supported these mechanistic insights. Hence, our findings present strong evidence of JF's therapeutic potential in attenuating MASH and MASH-HCC, warranting further investigation of JF's efficacy as a dietary intervention in clinical trials.
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Affiliation(s)
- Diwakar Suresh
- Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, 570015, Karnataka, India
| | - Bharathwaaj Gunaseelan
- Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, 570015, Karnataka, India
| | - Akshatha N Srinivas
- Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, 570015, Karnataka, India
| | - Amith Bharadwaj
- Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, 570015, Karnataka, India
| | - James Joseph
- God's Own Food Solutions Pvt Ltd, Kochi, 683585, Kerala, India
| | - Megha
- Centre For Ayurveda Biology and Holistic Nutrition, University of Transdisciplinary Health Sciences and Technology, Bangalore, 560064, India
| | - Thomas Varughese
- Department of Surgical Oncology, St. Joseph's Hospital Trust, Manjummel, Kochi, 683501, Kerala, India
| | - Suchitha Satish
- Department of Pathology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, 570015, Karnataka, India
| | - Deepak Suvarna
- Department of Gastroenterology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, 570015, Karnataka, India
| | - Prasanna K Santhekadur
- Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, 570015, Karnataka, India
| | - Saravana Babu Chidambaram
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012, India
| | - Divya P Kumar
- Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and Research, SS Nagar, Mysuru, 570015, Karnataka, India.
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13
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Milani I, Chinucci M, Leonetti F, Capoccia D. MASLD: Prevalence, Mechanisms, and Sex-Based Therapies in Postmenopausal Women. Biomedicines 2025; 13:855. [PMID: 40299427 PMCID: PMC12024897 DOI: 10.3390/biomedicines13040855] [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: 03/08/2025] [Revised: 03/27/2025] [Accepted: 03/31/2025] [Indexed: 04/30/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease influenced by genetic, lifestyle, and environmental factors. While MASLD is more prevalent in men, women are at increased risk after menopause, highlighting the critical pathogenetic role of sex hormones. The complex interplay between estrogen deficiency, visceral fat accumulation, metabolic syndrome (MetS), and inflammation accelerates disease progression, increases cardiovascular (CV) risk, and triggers a cycle of worsening adiposity, metabolic dysfunction, and psychological problems, including eating disorders. Weight loss in postmenopausal women can significantly improve both metabolic and psychological outcomes, helping to prevent MASLD and related conditions. This review examines the prevalence of MASLD, its comorbidities (type 2 diabetes T2D, CV, mental disorders), pathogenetic mechanisms, and pharmacological treatment with GLP-1 receptor agonists (GLP1-RAs), with a focus on postmenopausal women. Given the use of GLP1-RAs in the treatment of obesity and T2D in MASLD patients, and the increase in MetS and MASLD after menopause, this review analyzes the potential of a stable GLP-1-estrogen conjugate as a therapeutic approach in this subgroup. By combining the synergistic effects of both hormones, this dual agonist has been shown to increase food intake and food reward suppression, resulting in greater weight loss and improved insulin sensitivity, glucose, and lipid metabolism. Therefore, we hypothesize that this pharmacotherapy may provide more targeted therapeutic benefits than either hormone alone by protecting the liver, β-cells, and overall metabolic health. As these effects are only supported by preclinical data, this review highlights the critical need for future research to evaluate and confirm the mechanisms and efficacy in clinical settings, particularly in postmenopausal women.
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Affiliation(s)
- Ilaria Milani
- Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, University of Rome La Sapienza, 04100 Latina, Italy; (M.C.); (F.L.); (D.C.)
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14
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Nakamura T, Masuda A, Nakano D, Amano K, Sano T, Nakano M, Kawaguchi T. Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma. Cells 2025; 14:428. [PMID: 40136677 PMCID: PMC11941585 DOI: 10.3390/cells14060428] [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: 12/19/2024] [Revised: 02/25/2025] [Accepted: 03/12/2025] [Indexed: 03/27/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer deaths worldwide. The etiology of HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). The main pathogenesis of MASLD-related HCC is the hepatic lipid accumulation of hepatocytes, which causes chronic inflammation and the subsequent progression of hepatic fibrosis. Chronic hepatic inflammation generates oxidative stress and DNA damage in hepatocytes, which contribute to genomic instability, resulting in the development of HCC. Several metabolic and molecular pathways are also linked to chronic inflammation and HCC in MASLD. In particular, the MAPK and PI3K-Akt-mTOR pathways are upregulated in MASLD, promoting the survival and proliferation of HCC cells. In addition, MASLD has been reported to enhance the development of HCC in patients with chronic viral hepatitis infection. Although there is no approved medication for MASLD besides resmetirom in the USA, there are some preventive strategies for the onset and progression of HCC. Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class of medications, has been reported to exert anti-tumor effects on HCC by regulating metabolic reprogramming. Moreover, CD34-positive cell transplantation improves hepatic fibrosis by promoting intrahepatic angiogenesis and supplying various growth factors. Furthermore, exercise improves MASLD through an increase in energy consumption as well as changes in chemokines and myokines. In this review, we summarize the recent progress made in the pathogenic mechanisms of MASLD-associated HCC. Furthermore, we introduced new therapeutic strategies for preventing the development of HCC based on the pathogenesis of MASLD.
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Affiliation(s)
- Toru Nakamura
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
- Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, Kurume University, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Atsutaka Masuda
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
- Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, Kurume University, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
- Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, Kurume University, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
- Fukuoka Consulting and Support Center for Liver Diseases, Kurume 830-0011, Japan
| | - Tomoya Sano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
- Fukuoka Consulting and Support Center for Liver Diseases, Kurume 830-0011, Japan
| | - Masahito Nakano
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan; (T.N.); (A.M.); (D.N.); (K.A.); (T.S.); (M.N.)
- Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, Kurume University, 67 Asahi-Machi, Kurume 830-0011, Japan
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15
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Huang DQ, Wong VWS, Rinella ME, Boursier J, Lazarus JV, Yki-Järvinen H, Loomba R. Metabolic dysfunction-associated steatotic liver disease in adults. Nat Rev Dis Primers 2025; 11:14. [PMID: 40050362 DOI: 10.1038/s41572-025-00599-1] [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] [Accepted: 02/07/2025] [Indexed: 03/09/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the umbrella term that comprises metabolic dysfunction-associated steatotic liver, or isolated hepatic steatosis, through to metabolic dysfunction-associated steatohepatitis, the progressive necroinflammatory disease form that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. MASLD is estimated to affect more than one-third of adults worldwide. MASLD is closely associated with insulin resistance, obesity, gut microbial dysbiosis and genetic risk factors. The obesity epidemic and the growing prevalence of type 2 diabetes mellitus greatly contribute to the increasing burden of MASLD. The treatment and prevention of major metabolic comorbidities such as type 2 diabetes mellitus and obesity will probably slow the growth of MASLD. In 2023, the field decided on a new nomenclature and agreed on a set of research and action priorities, and in 2024, the US FDA approved the first drug, resmetirom, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis. Reliable, validated biomarkers that can replace histology for patient selection and primary end points in MASH trials will greatly accelerate the drug development process. Additionally, noninvasive tests that can reliably determine treatment response or predict response to therapy are warranted. Sustained efforts are required to combat the burden of MASLD by tackling metabolic risk factors, improving risk stratification and linkage to care, and increasing access to therapeutic agents and non-pharmaceutical interventions.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Vincent W S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Mary E Rinella
- University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - Jerome Boursier
- Service d'Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, France
- Laboratoire HIFIH, SFR ICAT 4208, Université d'Angers, Angers, France
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
- City University of New York Graduate School of Public Health and Health Policy, New York, NY, USA
| | - Hannele Yki-Järvinen
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Rohit Loomba
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA.
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA.
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Boel F, Akimov V, Teuchler M, Terkelsen MK, Wernberg CW, Larsen FT, Hallenborg P, Lauridsen MM, Krag A, Mandrup S, Ravnskjær K, Blagoev B. Deep proteome profiling of metabolic dysfunction-associated steatotic liver disease. COMMUNICATIONS MEDICINE 2025; 5:56. [PMID: 40032974 PMCID: PMC11876662 DOI: 10.1038/s43856-025-00780-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 02/21/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) affects roughly 1 in 3 adults and is a leading cause of liver transplants and liver related mortality. A deeper understanding of disease pathogenesis is essential to assist in developing blood-based biomarkers. METHODS Here, we use data-independent acquisition mass spectrometry to assess disease-state associated protein profiles in human liver, blood plasma, and white adipose tissue (WAT). RESULTS In liver, we find that MASLD is associated with an increased abundance of proteins involved in immune response and extracellular matrix (ECM) and a decrease in proteins involved in metabolism. Cell type deconvolution of the proteome indicates liver endothelial and hepatic stellate cells are the main source of ECM rearrangements, and hepatocytes are the major contributor to the changes in liver metabolism. In the blood, profiles of several MASLD-associated proteins correlate with expression in WAT rather than liver and so could serve as suitable liver disease predictors in a multi-protein panel marker. Moreover, our proteomics-based logistic regression models perform better than existing methods for predicting MASLD and liver fibrosis from human blood samples. CONCLUSIONS Our comprehensive proteomic analysis deepens the understanding of liver function and MASLD pathology by elucidating key cellular mechanisms and multi-organ interactions, and demonstrates the robustness of a proteomics-based biomarker panel to enhance diagnosis of MASLD and significant fibrosis.
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Affiliation(s)
- Felix Boel
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Vyacheslav Akimov
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Mathias Teuchler
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Mike Krogh Terkelsen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Charlotte Wilhelmina Wernberg
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
- Department of Gastroenterology and Hepatology, University Hospital of Southern Denmark, Esbjerg, Denmark
| | - Frederik Tibert Larsen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Philip Hallenborg
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
| | - Mette Munk Lauridsen
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
- Department of Gastroenterology and Hepatology, University Hospital of Southern Denmark, Esbjerg, Denmark
| | - Aleksander Krag
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense M, Denmark
| | - Susanne Mandrup
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Kim Ravnskjær
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Blagoy Blagoev
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark.
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Elrashdy F, Mohamed R, Cordie A, Abdel Aziz H, Mohamed N, Kamel A, Ramadan A, Hamdy M, Yasser M, Meshaal S, Abdel Alem S, Elsharkawy A, Esmat G. A Comparison of Metabolic-Associated Fatty Liver Disease and Steatotic Liver Disease in a Cohort of Egyptian People Living with Human Immunodeficiency Virus. Metab Syndr Relat Disord 2025; 23:97-102. [PMID: 39967462 DOI: 10.1089/met.2024.0184] [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: 02/20/2025] Open
Abstract
Background: The prevalence of fatty liver disease in people living with human immunodeficiency virus (PLHIV) is significantly higher than in general population. This study aims to compare the burden of fatty liver disease in Egyptian PLHIV using both metabolic dysfunction-associated fatty liver disease (MAFLD) and steatotic liver disease (SLD) criteria. Methods: A retrospective cross-sectional study was conducted on PLHIV attending the HIV reference center at Embaba Fever Hospital in Egypt between November 2019 and July 2021. Data collection included demographics, comorbidities, physical examination, laboratory tests, liver ultrasound, controlled attenuation parameter, and liver stiffness measurement using Fibroscan®. Results: The prevalence of SLD and MAFLD was 26.92% and 21.15%, respectively. The concordance between MAFLD and SLD definitions was low (kappa = 0.465). The presence of SLD was significantly associated with increased odds of significant fibrosis (P = 0.045). However, MAFLD was not significantly associated with fibrosis (P = 0.369). Conclusion: SLD demonstrates a stronger association with significant fibrosis than MAFLD in PLHIV. This highlights the potential of SLD as a more inclusive and representative classification for steatosis in PLHIV.
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Affiliation(s)
- Fatma Elrashdy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rahma Mohamed
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Kasr Al-Aini HIV and Viral Hepatitis Fighting Group, Cairo University Hospitals, Cairo University, Cairo, Egypt
| | - Ahmed Cordie
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Kasr Al-Aini HIV and Viral Hepatitis Fighting Group, Cairo University Hospitals, Cairo University, Cairo, Egypt
| | - Hossam Abdel Aziz
- Hepatology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Naema Mohamed
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kamel
- Clinical Pharmacy Department, Faculty of pharmacy, Cairo University, Cairo, Egypt
| | - Ahmed Ramadan
- Department of Chemical & Biotechnology Engineering, Faculty of Engineering, Université de Sherbrooke, Sherbrooke, Canada
| | - Mohamed Hamdy
- Infectious Disease Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | | | - Safa Meshaal
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Shereen Abdel Alem
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Aisha Elsharkawy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Research Center, Badr University in Cairo, Badr City, Egypt
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Wang T, Liu B, Huang J, Zhao Q, Shen H, Bi T, Liu Z, Dai Y, Sun Q. IFN-γ-mediated inhibition of JAK/STAT signaling via nano-scutellarin treatment is an efficient strategy for ameliorating liver fibrosis. J Transl Med 2025; 23:195. [PMID: 39962553 PMCID: PMC11834254 DOI: 10.1186/s12967-025-06155-5] [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] [Accepted: 01/18/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatohepatitis (MASH) is a large group of metabolic diseases that are hazardous to human health. Endothelial-to-mesenchymal transition (EndMT) mediated myofibroblast activation is an important factor that aggravates the development of liver fibrosis during MASH. However, the limited understanding of the underlying molecular mechanisms that drive EndMT in MASH has hindered the development of molecularly targeted therapies specifically targeting this pathological process. METHODS We employed wild-type and ifn-γ-deficient mice, MASH models were induced repeated CCl4 injections and a high-fat diet to verify the significance of IFN-γ role in vivo and its impact in EndMT. Male mice models of MASH were used to further analyze the effect of Scutellarin@BSA on the improvement of liver fibrosis during MASH in vivo and HUVECs were used to assess IFN-γ effect on EndMT and its interaction with JAK signaling pathway in vitro. RESULTS The results showed that IFN-γ is revealed as a key regulator of EndMT during MASH, as evidenced by the significantly lower levels of EndMT and reduced pathological damage in the livers of ifn-γ knockout mice. Furthermore, our research has led to the development of Scutellarin@BSA therapy, which targets and mitigates IFN-γ-driven EndMT, which showed excellent therapeutic effects on EndMT and liver fibrosis in vivo and in vitro during MASH. Mechanistically, IFN-γ can directly bind to the JAK protein and activate downstream STAT1 transcription factors, exerting transcriptional activity and further driving the expression of EndMT-associated proteins. Notably, Scutellarin@BSA treatment effectively diminishes the hallmarks of liver fibrosis by modulating the canonical JAK/STAT1 signaling pathway. CONCLUSIONS IFN-γ was identified as a key regulator of EndMT, and Scutellarin@BSA, as an emerging treatment, has been found to effectively inhibit EndMT by directly targeting the regulatory influence of the IFN-γ signaling. This result demonstrates significant therapeutic efficacy in alleviating hepatic fibrosis during MASH, highlighting its great potential as an innovative liver fibrosis treatment.
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Affiliation(s)
- Ting Wang
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Bangguo Liu
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Juan Huang
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Qixin Zhao
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Hongping Shen
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Tao Bi
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
- State Key Laboratories for Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 853, China
| | - Zengjin Liu
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Yong Dai
- Sichuan Police College, Luzhou, 646000, Sichuan, China.
| | - Qin Sun
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
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19
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Yun B, Park H, Ahn SH, Oh J, Kim BK, Yoon JH. Liver Cancer Risk Across Metabolic Dysfunction-Associated Steatotic Liver Disease and/or Alcohol: A Nationwide Study. Am J Gastroenterol 2025; 120:410-419. [PMID: 38934496 DOI: 10.14309/ajg.0000000000002920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024]
Abstract
INTRODUCTION New terminologies of metabolic dysfunction-associated steatotic liver disease (MASLD) have been developed. We assessed hepatocellular carcinoma (HCC) risk across MASLD and/or alcohol intake. METHODS We included participants aged 40-79 years receiving a national health checkup from 2009 to 2010 in the Republic of Korea, classified as follows: non-MASLD, MASLD, MASLD with increased alcohol intake (MetALD; weekly alcohol 210-420 g for male and 140-350 g for female individuals), and alcohol-associated liver disease (ALD; excessive alcohol intake with weekly alcohol ≥420 g for male or ≥350 g for female individuals). The primary outcome was HCC incidence. HCC risk was estimated using multivariable Cox proportional hazard models. RESULTS Among 6,412,209 participants, proportions of non-MASLD, MASLD, MetALD, and ALD cases were 59.5%, 32.4%, 4.8%, and 3.4%, respectively. During follow-up (median 13.3 years), 27,118 had newly developed HCC. Compared with non-MASLD, the HCC risk increased from MASLD (adjusted hazard ratio [aHR] 1.66, 95% confidence interval [CI] 1.62-1.71) and MetALD (aHR 2.17, 95% CI 2.08-2.27) to ALD (aHR 2.34, 95% CI 2.24-2.45) in a stepwise manner. Furthermore, the older and non-cirrhosis subgroups were more vulnerable to detrimental effects of MASLD and/or alcohol intake, concerning HCC risk. Among the older, female, and cirrhosis subgroups, MetALD poses similar HCC risks as ALD. DISCUSSION HCC risk increased from MASLD and MetALD to ALD in a stepwise manner, compared with non-MASLD. For an effective primary prevention of HCC, a comprehensive approach should be required to modify both metabolic dysfunction and alcohol intake habit.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul, Republic of Korea
| | - Heejoo Park
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Juyeon Oh
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul, Republic of Korea
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Elsabaawy M, Naguib M, Abuamer A, Shaban A. Comparative application of MAFLD and MASLD diagnostic criteria on NAFLD patients: insights from a single-center cohort. Clin Exp Med 2025; 25:36. [PMID: 39808219 PMCID: PMC11732950 DOI: 10.1007/s10238-024-01553-3] [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: 11/14/2024] [Accepted: 12/28/2024] [Indexed: 01/16/2025]
Abstract
The diagnostic criteria for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Metabolic Associated Steatotic Liver Disease (MASLD) aim to refine the classification of fatty liver diseases previously grouped under Non-Alcoholic Fatty Liver Disease (NAFLD). This study evaluates the applicability of the MAFLD and MASLD frameworks in NAFLD patients, exploring their clinical utility in identifying high-risk patients. A total of 369 NAFLD patients were assessed using MAFLD and MASLD diagnostic criteria. Baseline characteristics, metabolic profiles, hepatic fibrosis, and cardiovascular risks were compared across the groups. Among NAFLD patients, 97.55% (n = 359) met MASLD criteria, and 97.01% (n = 357) fulfilled MAFLD criteria. Both frameworks MAFLD and MASLD captured overlapping populations, with MASLD encompassing slightly more cases. No significant differences were observed in metabolic risk factors, fibrosis indices (APRI, FIB-4, NAFLD fibrosis score), or cardiovascular risk (10-year ASCVD score). A small subset of lean NAFLD patients (10 cases) with distinct profiles remained uncategorized by either framework. Pure NAFLD cases (n = 10) were with mild insulin resistance (HOMA-IR: 3.07 ± 0.33) and slightly elevated LDL (102.5 ± 42.87 mg/dL), while fibrosis indices indicated low fibrosis risk. Steatosis indices supported the diagnosis of early-stage NAFLD with preserved liver function. These patients do not meet the criteria for inclusion in the MAFLD or MASLD frameworks, highlighting a gap in the current diagnostic systems. MAFLD and MASLD criteria align closely with NAFLD in capturing patients with metabolic risk with MASLD-enhanced inclusivity. Further refinement is required to address heterogeneity, particularly in lean NAFLD patients. Hypertension prevalence was comparable (17.4% in NAFLD, 18.2% in MAFLD, 17.8% in MASLD; p = 0.960), as was diabetes mellitus (36.7%, 37.8%, and 37.6%, respectively; p = 0.945). Body mass index was also similar across groups, with medians of 33.25, 33.6, and 33.4 kg/m2 (p = 0.731). Non-invasive markers of hepatic fibrosis, including APRI, FIB-4, and NAFLD fibrosis scores, did not differ significantly, with median FIB-4 scores around 1.05 (p = 0.953). Similarly, were the results of hepatic steatosis index and ASCVD score.
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Affiliation(s)
- Maha Elsabaawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Menoufia, Egypt.
| | - Madiha Naguib
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Menoufia, Egypt
| | - Ahmed Abuamer
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Menoufia, Egypt
| | - Ahmed Shaban
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Menoufia, Egypt
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De A, Bhagat N, Mehta M, Singh P, Rathi S, Verma N, Taneja S, Premkumar M, Duseja A. Central Obesity is an Independent Determinant of Advanced Fibrosis in Lean Patients With Nonalcoholic Fatty Liver Disease. J Clin Exp Hepatol 2025; 15:102400. [PMID: 39282592 PMCID: PMC11399567 DOI: 10.1016/j.jceh.2024.102400] [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: 09/09/2023] [Accepted: 08/03/2024] [Indexed: 09/19/2024] Open
Abstract
Background The current definition of lean is based on body mass index (BMI). However, BMI is an imperfect surrogate for adiposity and provides no information on central obesity (CO). Hence, we explored the differences in clinical profile and liver disease severity in lean patients with nonalcoholic fatty liver disease (NAFLD) with and without CO. Methods One hundred seventy lean patients with NAFLD (BMI <23 kg/m2) were divided into two groups depending upon the presence or absence of CO (waist circumference ≥80 cm in females and ≥90 cm in males). Noninvasive assessment of steatosis was done by ultrasound and controlled attenuation parameter (CAP), while fibrosis was assessed with FIB-4 and liver stiffness measurement (LSM). FibroScan-AST (FAST) score was used for non-invasive prediction of NASH with significant fibrosis. Results Of 170 patients with lean NAFLD, 96 (56.5%) had CO. Female gender (40.6% vs. 17.6%, P = 0.001), hypertriglyceridemia (58.3% vs. 39.2%, P = 0.01) and metabolic syndrome (23.9% vs. 4.1%, P < 0.001) were more common in the CO group. There was a poor correlation between BMI and waist circumference (r = 0.24, 95% CI: 0.09-0.38). Grade 2-3 steatosis on ultrasound was significantly more common in CO patients (30% vs. 12.3%, P = 0.007). CAP [312.5 (289.8-341) dB/m vs. 275 (248-305.1) dB/m, P = 0.002], FAST score [0.42 (0.15-0.66) vs. 0.26 (0.11-0.39), P = 0.04], FIB-4 and LSM were higher in those with CO. Advanced fibrosis was more prevalent among CO patients using FIB-4 (19.8% vs 8.1%, P = 0.03) and LSM (9.5% vs. 0, P = 0.04). CO was independently associated with advanced fibrosis after adjusting for BMI and metabolic risk factors (aOR: 3.11 (1.10-8.96), P = 0.03). Among these 170 patients, 142 fulfilled metabolic dysfunction associated steatotic liver disease (MASLD) criteria. CO was also an independent risk factor for advanced fibrosis in MASLD (3.32 (1.23-8.5), P = 0.02). Conclusion Lean patients with NAFLD or MASLD and CO have more severe liver disease compared to those without CO.
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Affiliation(s)
- Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Naveen Bhagat
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manu Mehta
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Priya Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Noreen S, Hashmi B, Tufail T, Ikram A, Arshad MT, Gnedeka KT. Synergistic Beneficial Effects of Flaxseed ( Linum usitatissimum L.) Oil and Olive ( Olea europaea L.) Oil Against Metabolic Dysfunction Associated Fatty Liver and Its Complications. Food Sci Nutr 2025; 13:e4638. [PMID: 39803256 PMCID: PMC11717047 DOI: 10.1002/fsn3.4638] [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: 09/05/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 01/16/2025] Open
Abstract
Flaxseed and olive oil effectively treat numerous diseases and health conditions, particularly metabolic disorders. Traditional medicine has used both oils for managing cardiovascular disease, diabetes, gastrointestinal dysfunctions, metabolic-dysfunction-associated fatty liver disease (MAFLD), obesity, and more. This review explores the bioactive and polyphenolic compounds in flaxseed and olive oils that provide anti-inflammatory, antioxidant, anti-microbial, hepatoprotective, cardioprotective, antidiabetic, and gastroprotective benefits. Flaxseed oil contains beneficial compounds like alpha-linolenic acid (ALA), lignans, ferulic acid, p-coumaric acid, and phytosterols. It contributes to its therapeutic effects on fatty liver disease and other conditions. Olive oil contains phenolic compounds, including oleic acid, hydroxytyrosol, and tocopherols, which are similarly linked to metabolic health benefits, especially in managing MAFLD. The purpose of this review is to elucidate the mechanisms of action of these bioactive compounds, highlighting their potential in managing various metabolic diseases.
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Affiliation(s)
- Sana Noreen
- University Institute of Diet and Nutritional SciencesThe University of LahoreLahorePakistan
| | - Bushra Hashmi
- University Institute of Diet and Nutritional SciencesThe University of LahoreLahorePakistan
| | - Tabussam Tufail
- University Institute of Diet and Nutritional SciencesThe University of LahoreLahorePakistan
| | - Ali Ikram
- University Institute of Food Science and TechnologyThe University of LahoreLahorePakistan
| | - Muhammad Tayyab Arshad
- University Institute of Food Science and TechnologyThe University of LahoreLahorePakistan
| | - Kodjo Théodore Gnedeka
- Togo Laboratory: Applied Agricultural Economics Research Team (ERE2A)University of LoméLoméTogo
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Li F, Wu M, Wang F, Luo L, Wu Z, Huang Z, Wen Z. Unveiling the endocrine connections of NAFLD: evidence from a comprehensive mendelian randomization study. Biomed Eng Lett 2025; 15:239-248. [PMID: 39781064 PMCID: PMC11704114 DOI: 10.1007/s13534-024-00442-8] [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: 08/18/2024] [Revised: 10/17/2024] [Accepted: 10/29/2024] [Indexed: 01/03/2025] Open
Abstract
Background NAFLD is gaining recognition as a complex, multifactorial condition with suspected associations with endocrine disorders. This investigation employed MR analysis to explore the potential causality linking NAFLD to a spectrum of endocrine diseases, encompassing T1D, T2D, obesity, graves' disease, and acromegaly. Methods Our methodology leveraged a stringent IV selection process, adhering to the STROBE-MR guidelines. The MR analysis was conducted utilizing three distinct methods: IVW, WM, and MR-Egger. The IVW method was prioritized as the primary analytical approach. We conducted MR analyses to analyze the causal relationship between NAFLD and metabolic disorders. We also examined 1400 metabolites implicated in NAFLD. Metabolic pathway analysis was performed using the MetaboAnalyst database. Results The findings indicated that T2D (OR = 1.211, 95%CI: 0.836-1.585) and obesity (OR = 1.245, 95%CI: 0.816-1.674) are associated with an increased risk of NAFLD development. Further exploration into the the 1400 metabolites revealed that cys-gly and diacetylornithine are predictive of NAFLD, T2D, and obesity, whereas isovalerylcarnitine exhibited an inverse association, potentially inhibiting disease development. Metabolic pathways involving alanine, aspartate, and glutamate metabolism were identified as pivotal regulators in the pathophysiology of NAFLD, T2D, and obesity. Conclusion The present study generated innovative viewpoints on the etiology of NAFLD. Our findings underscore the significant role of T2D and obesity in NAFLD pathogenesis through metabolic pathways, presenting opportunities for targeted therapeutic strategies and warranting further investigation. Supplementary Information The online version contains supplementary material available at 10.1007/s13534-024-00442-8.
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Affiliation(s)
- Fan Li
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Mingjun Wu
- Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China
| | - Fenfen Wang
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Linfei Luo
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Zhengqiang Wu
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Zixiang Huang
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Zhili Wen
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
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Guan C, Zou X, Shi W, Gao J, Yang C, Ge Y, Xu Z, Bi S, Zhong X. Metallothionein 1B attenuates inflammation and hepatic steatosis in MASH by inhibiting the AKT/PI3K pathway. J Lipid Res 2025; 66:100701. [PMID: 39551239 PMCID: PMC11714418 DOI: 10.1016/j.jlr.2024.100701] [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: 08/05/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 11/19/2024] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is a severe form of metabolic dysfunction-associated fatty liver disease metabolic dysfunction-associated steatohepatitis , characterized by hepatic steatosis, inflammation, and fibrosis. This study investigates the role and potential mechanisms of metallothionein 1B (MT1B) in MASH through bioinformatics analysis and experimental validation. quantitative reverse transcription PCR and Western blot analyses confirm that MT1B expression is significantly downregulated in liver tissues of MASH patients, in high-fat diet-induced mouse models, and in hepatocytes induced by FFAs. Further functional experiments show that upregulation of MT1B reduces intracellular triglycerides and total cholesterol levels, lipid droplet formation, and proinflammatory factors. In vivo experiments demonstrate that specific downregulation of hepatic MT1B expression via AAV8-shMT1B injection significantly increases triglyceride and total cholesterol levels, exacerbates lipid accumulation, and markedly elevates liver fibrosis and inflammatory factor expression. RNA-seq and bioinformatics analyses show that the AKT/PI3K pathway is significantly suppressed in MT1B-overexpressing cells. Further experiments indicate that AKT inhibition can reverse the lipid metabolism disorders and inflammatory responses caused by MT1B downregulation. Additionally, Zinc can promote the nuclear translocation of MTF1, leading to its binding to the MT1B promoter, thereby upregulating MT1B expression and ultimately mitigating MASH progression. These findings suggest that zinc-regulated MT1B plays a critical role in lipid metabolism and inflammatory responses by regulating the AKT/PI3K signaling pathway, influencing MASH progression.
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Affiliation(s)
- Canghai Guan
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang, China
| | - Xinlei Zou
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Wujiang Shi
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Jianjun Gao
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Chengru Yang
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Yifei Ge
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Zhaoqiang Xu
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Shaowu Bi
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Xiangyu Zhong
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
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Niu QQ, Xi YT, Zhang CR, Li XY, Li CZ, Wang HD, Li P, Yin YL. Potential mechanism of perillaldehyde in the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking. Eur J Pharmacol 2024; 985:177092. [PMID: 39510336 DOI: 10.1016/j.ejphar.2024.177092] [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: 05/30/2024] [Revised: 10/08/2024] [Accepted: 10/31/2024] [Indexed: 11/15/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic metabolic liver diseases worldwide. Perillaldehyde (4-propyl-1-en-2-ylcyclohexene-1-aldehyde, PA) is a terpenoid compound extracted from Perilla, which has effective pharmacological activities such as anti-inflammatory, antidepressant, and anticancer. This study aimed to explore the pharmacological effects of PA in intervening with NAFLD and reveal its potential mechanisms. Firstly, we identified the core targets of PA intervention therapy for NAFLD through network pharmacology and molecular docking techniques. After that, in vitro animal experiments such as H&E and Masson staining, immunofluorescence, immunohistochemistry, and Western blot were conducted to validate the results network effectively pharmacology predicted. Network pharmacology analysis suggested that PPAR-α may be the core target of PA intervention in NAFLD. H&E and Masson staining showed that after low-dose (50 mg/kg) PA administration, there was a noticeable improvement in fat deposition in the livers of NAFLD mice, and liver tissue fibrosis was alleviated. Immunohistochemical and immunofluorescence analysis showed that low dose (50 mg/kg) PA could reduce hepatocyte apoptosis, decrease the content of pro-apoptosis protein Bax, and increase the expression of anti-apoptosis protein Bcl-2 in NAFLD mice. Western blot results confirmed that low-dose (50 mg/kg) PA could increase the expression of PPAR-α and inhibit the expression of NF-κB in NAFLD mice. Our study indicated that PA could enhance the activity of PPAR-α and reduce the level of NF-κB in NAFLD mice, which may positively affect the prevention of NAFLD.
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Affiliation(s)
- Qian-Qian Niu
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China; Department of Toxicology, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, 13200, Malaysia
| | - Yu-Ting Xi
- Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, 453003, China
| | - Chun-Rui Zhang
- Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, 453003, China
| | - Xi-Yue Li
- Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, 453003, China
| | - Cheng-Zhi Li
- Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, 453003, China
| | - Hui-Dan Wang
- Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, 453003, China
| | - Peng Li
- Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, 453003, China.
| | - Ya-Ling Yin
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
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Deng Q, Zhang Y, Guan X, Wang C, Guo H. Association of healthy lifestyles with risk of all-cause and cause-specific mortality among individuals with metabolic dysfunction-associated steatotic liver disease: results from the DFTJ cohort. Ann Med 2024; 56:2398724. [PMID: 39247937 PMCID: PMC11385647 DOI: 10.1080/07853890.2024.2398724] [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: 10/08/2023] [Revised: 06/18/2024] [Accepted: 07/19/2024] [Indexed: 09/10/2024] Open
Abstract
AIM To examine the associations of healthy lifestyles with risk of all-cause and cause-specific mortality among adults with metabolic dysfunction-associated steatotic liver disease (MASLD), and whether the association was mediated by systemic immune-inflammatory biomarkers (SIIBs). METHODS The study included 10,347 subjects with MASLD, who were enrolled in the Dongfeng-Tongji cohort study. The healthy lifestyles referred to non-smoking, being physically active (≥7.5 metabolic equivalents-hours/week), low-risk alcohol consumption (1-14 g/day for women and 1-28 g/day for men), and optimal sleep duration (≥6 to ≤8 h/day). Cox proportional hazard models were used to examine the relationship between each lifestyle and SIIBs with the risk of all-cause and cause-specific mortality. A mediation analysis was conducted to investigate the role of SIIBs on the association between healthy lifestyles and mortality. RESULTS There were 418 MASLD subjects dead till the follow-up of 2018, including 259 deaths from cardiovascular disease (CVD). Compared to MASLD participants with 0-1 healthy lifestyle score (HLS), those with 3-4 HLS had the lowest risk of all-cause mortality [hazard ratio (HR), 0.46; 95% CI, (0.36-0.60)], and CVD mortality [HR (95%CI), 0.41 (0.29-0.58)]. Mediation analyses indicated that SIIBs mediated the association between healthy lifestyles and mortality, with proportions ranging from 2.5% to 6.1%. CONCLUSIONS These findings suggest that adherence to healthy lifestyles can significantly reduce mortality for MASLD patients, and the decreased SIIBs may partially explain the protection mechanism of healthy lifestyles.
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Affiliation(s)
- Qilin Deng
- Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yingchen Zhang
- Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Guan
- Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chenming Wang
- Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huan Guo
- Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Jiang M, Pan Z, George J, Eslam M. Clinical features and mortality outcomes of patients with MASLD only compared to those with MAFLD and MASLD. Hepatol Int 2024; 18:1731-1739. [PMID: 39196505 DOI: 10.1007/s12072-024-10721-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 08/08/2024] [Indexed: 08/29/2024]
Abstract
BACKGROUND AND AIMS The applicability of the proposed metabolic dysfunction-associated steatotic liver disease (MASLD) definition has not been validated. We aimed to characterize the profiles and long-term survival of people meeting the criteria for MASLD, but not that of metabolic dysfunction-associated fatty liver disease (MAFLD), i.e. MASLD only. METHODS Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, 7791 adult participants were included and categorized into four distinct groups: no SLD, non-MAFLD MASLD, MASLD-MAFLD, and cryptogenic SLD (steatosis without metabolic dysfunction). RESULTS Participants in the MASLD-only group were younger and had better metabolic profiles and fibrosis degree compared to those with MASLD-MAFLD and those with no SLD. Their profiles were comparable to those with cryptogenic SLD. Similarly, the MASLD-only group tend to have lower cumulative incidence of all-cause and cardiovascular mortality. Clustering analysis showed that MASLD only clusters differently from individuals with MASLD-MAFLD. CONCLUSIONS MASLD only is a distinct clinical group with substantial heterogeneity compared to those captured using the MAFLD criteria.
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Affiliation(s)
- Mingqian Jiang
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
- Department of Endocrinology and Metabolism, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Ziyan Pan
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia.
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Kaylan KB, Paul S. NAFLD No More: A Review of Current Guidelines in the Diagnosis and Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Curr Diab Rep 2024; 25:5. [PMID: 39535566 DOI: 10.1007/s11892-024-01558-y] [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] [Accepted: 10/10/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE OF REVIEW Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation. RECENT FINDINGS Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications. MASLD has been increasing in prevalence and disease burden but is underrecognized in primary care and endocrinology clinics. Multiple society guidelines, synthesized here, provide a framework for the initial approach in the diagnosis and evaluation of MASLD. Recent advances in pharmacologic treatment underline the importance of screening for patients who are at risk for advanced fibrosis as they are most likely to benefit from new drug classes, such as the liver-directed thyroid receptor agonist resmiterom.
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Affiliation(s)
- Kerim B Kaylan
- Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago Medicine, Chicago, IL, USA
| | - Sonali Paul
- Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA.
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Bae J, Han E, Lee HW, Park CY, Chung CH, Lee DH, Cho EH, Rhee EJ, Yu JH, Park JH, Bae JC, Park JH, Choi KM, Kim KS, Seo MH, Lee M, Kim NH, Kim SH, Lee WY, Lee WJ, Choi YK, Lee YH, Hwang YC, Lyu YS, Lee BW, Cha BS, on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association. Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association. Diabetes Metab J 2024; 48:1015-1028. [PMID: 39610131 PMCID: PMC11621661 DOI: 10.4093/dmj.2024.0541] [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: 09/06/2024] [Accepted: 10/23/2024] [Indexed: 11/30/2024] Open
Abstract
Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist's perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.
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Affiliation(s)
- Jaehyun Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hye Won Lee
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
| | - Cheol-Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hee Chung
- Department of Internal Medicine and Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dae Ho Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Eun-Hee Cho
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Eun-Jung Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Ji-Cheol Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Jung Hwan Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kyung-Soo Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Mi Hae Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
| | - Minyoung Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Nan-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yeon-Kyung Choi
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yong-ho Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - You-Cheol Hwang
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Young Sang Lyu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine and Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
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Guan C, Zou X, Yang C, Shi W, Gao J, Ge Y, Xu Z, Bi S, Zhong X. Polyribonucleotide nucleotidyltransferase 1 participates in metabolic-associated fatty liver disease pathogenesis by affecting lipid metabolism and mitochondrial homeostasis. Mol Metab 2024; 89:102022. [PMID: 39218215 PMCID: PMC11414560 DOI: 10.1016/j.molmet.2024.102022] [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: 07/03/2024] [Revised: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 09/04/2024] Open
Abstract
OBJECTIVE Metabolic-associated fatty liver disease (MAFLD) represents one of the most prevalent chronic liver conditions worldwide, but its precise pathogenesis remains unclear. This research endeavors to elucidate the involvement and molecular mechanisms of polyribonucleotide nucleotidyltransferase 1 (PNPT1) in the progression of MAFLD. METHODS The study employed western blot and qRT-PCR to evaluate PNPT1 levels in liver specimens from individuals diagnosed with MAFLD and in mouse models subjected to a high-fat diet. Cellular studies investigated the effects of PNPT1 on lipid metabolism, apoptosis, and mitochondrial stability in hepatocytes. Immunofluorescence was utilized to track the subcellular movement of PNPT1 under high lipid conditions. RNA immunoprecipitation and functional assays were conducted to identify interactions between PNPT1 and Mcl-1 mRNA. The role of PPARα as an upstream transcriptional regulator of PNPT1 was investigated. Recombinant adenoviral vectors were utilized to modulate PNPT1 expression in vivo. RESULTS PNPT1 was found to be markedly reduced in liver tissues from MAFLD patients and HFD mice. In vitro, PNPT1 directly regulated hepatic lipid metabolism, apoptosis, and mitochondrial stability. Under conditions of elevated lipids, PNPT1 relocated from mitochondria to cytoplasm, modifying its physiological functions. RNA immunoprecipitation revealed that the KH and S1 domains of PNPT1 bind to and degrade Mcl-1 mRNA, which in turn affects mitochondrial permeability. The transcriptional regulator PPARα was identified as a significant influencer of PNPT1, impacting both its expression and subsequent cellular functions. Alterations in PNPT1 expression were directly correlated with the progression of MAFLD in mice. CONCLUSIONS The study confirms the pivotal function of PNPT1 in the development of MAFLD through its interactions with Mcl-1 and its regulatory effects on lipid metabolism and mitochondrial stability. These insights highlight the intricate association between PNPT1 and MAFLD, shedding light on its molecular pathways and presenting a potential new therapeutic avenue for MAFLD management.
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Affiliation(s)
- Canghai Guan
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, 148 Baojian Street, Harbin 150086, Heilongjiang, China
| | - Xinlei Zou
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Chengru Yang
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Wujiang Shi
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Jianjun Gao
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Yifei Ge
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Zhaoqiang Xu
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Shaowu Bi
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China
| | - Xiangyu Zhong
- General Surgery Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Baojian Street, Harbin 150086, Heilongjiang Province, China.
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31
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Souza M, Diaz I, Al-Sharif L. Liver and cardiovascular outcomes in lean non-alcoholic fatty liver disease: an updated systematic review and meta-analysis of about 1 million individuals. Hepatol Int 2024; 18:1396-1415. [PMID: 39117942 DOI: 10.1007/s12072-024-10716-z] [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: 04/20/2024] [Accepted: 07/22/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) is present in lean people. However, the magnitude of the prognostic hepatic and cardiovascular risk in these patients compared to non-lean counterparts remains unclear. We aimed to investigate this topic, and to explore whether these risks change based on factors related to NAFLD severity. METHODS PubMed and Embase databases were searched for cohort studies (published through April 2024) that evaluated liver and cardiovascular (CV) outcomes in lean and non-lean individuals with NAFLD and reported unadjusted or adjusted data. We pooled risk ratios (RRs) or hazard ratios (HRs) using a random-effects modeling and performed subgroup and meta-regressions analyses. RESULTS We identified 22 studies with over 1 million NAFLD patients (13.0% were lean). Lean NAFLD showed a similar risk of liver-related events in unadjusted analysis (RR 1.08, 95% CI 0.79-1.49, I2 = 31%), but a higher risk in adjusted analysis (HR 1.66, 95% CI 1.17-2.36, I2 = 83%) compared to non-lean NAFLD. Lean NAFLD had a higher risk of liver-related mortality (RR 2.22, 95% CI 1.57-3.15, I2 = 0%; HR 2.26, 95% CI 1.14-4.51, I2 = 0%). For CV outcomes, lean NAFLD had a lower risk of any cardiovascular disease in unadjusted analysis (RR = 0.82, 95% CI 0.70-0.95, I2 = 88%), but similar risk in adjusted analysis (HR 0.89, 95% CI 0.77-1.02, I2 = 78%), and similar risk of cardiovascular mortality (RR 1.09, 95% CI 0.71-1.66, I2 = 85%; HR 1.26, 95% CI 0.89-1.78, I2 = 46%) compared to non-lean NAFLD. CONCLUSIONS Lean NAFLD patients have worse liver outcomes, but similar CV outcomes compared to non-lean NAFLD patients, highlighting the importance of monitoring both groups closely.
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Affiliation(s)
- Matheus Souza
- Department of Internal Medicine, Federal University of Rio de Janeiro, 255 Professor Rodolpho Paulo Rocco Av, Rio de Janeiro, 21941-913, Brazil.
| | - Ivanna Diaz
- Department of Internal Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA
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Allen AM, Younossi ZM, Diehl AM, Charlton MR, Lazarus JV. Envisioning how to advance the MASH field. Nat Rev Gastroenterol Hepatol 2024; 21:726-738. [PMID: 38834817 DOI: 10.1038/s41575-024-00938-9] [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] [Accepted: 05/02/2024] [Indexed: 06/06/2024]
Abstract
Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.
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Affiliation(s)
- Alina M Allen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA
- The Global NASH Council, Washington DC, USA
| | | | - Michael R Charlton
- Center for Liver Diseases, Department of Medicine, The University of Chicago, Chicago, IL, USA
| | - Jeffrey V Lazarus
- The Global NASH Council, Washington DC, USA.
- CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA.
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain.
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
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Zhou XD, Lonardo A, Pan CQ, Shapiro MD, Zheng MH. Clinical features and long-term outcomes of patients diagnosed with MASLD, MAFLD, or both. J Hepatol 2024; 81:e157-e159. [PMID: 38554846 DOI: 10.1016/j.jhep.2024.03.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/15/2024] [Accepted: 03/25/2024] [Indexed: 04/02/2024]
Affiliation(s)
- Xiao-Dong Zhou
- Department of Cardiovascular Medicine, The Heart Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | | | - Calvin Q Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University Grossman School of Medicine, New York, USA
| | - Michael D Shapiro
- Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, 325000, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, 325000, China.
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34
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De A, Mehta M, Duseja A. Substantial overlap between NAFLD and MASLD with comparable disease severity and non-invasive test performance: An analysis of the Indian Consortium on MASLD (ICOM-D) cohort. J Hepatol 2024; 81:e162-e164. [PMID: 38801919 DOI: 10.1016/j.jhep.2024.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 05/29/2024]
Affiliation(s)
- Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Manu Mehta
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
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35
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Iruzubieta P, Arias-Loste MT, Crespo J. Lights and shadows in the new definition of steatotic liver disease. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:523-525. [PMID: 39235184 DOI: 10.17235/reed.2024.10696/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/06/2024]
Abstract
The presence of marked hepatic steatosis in patients with high alcohol consumption was first described in 1836 by Addison et al.1 Many years later, in 1980, Ludwig and colleagues described a histological picture very similar to that seen in patients with alcoholic hepatitis but who did not consume alcohol, coining the term non-alcoholic steatohepatitis (NASH).2 In recent years, the terminology used to describe conditions related to hepatic steatosis has undergone significant evolution. In 2020, Eslam et al.3 subsequently modified it to MAFLD (Metabolic Associated Fatty Liver Disease) to better reflect its association with metabolic dysfunction, a nomenclature that, from the beginning, generated some reluctance due to the absence of clear international consensus.
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Affiliation(s)
- Paula Iruzubieta
- Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla. IDIVAL, 39002
| | | | - Javier Crespo
- Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla. IDIVAL, 39002
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Abenavoli L, Spagnuolo R, Scarlata GGM, Gambardella ML, Boccuto L, Méndez-Sánchez N, Luzza F. Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients with Inflammatory Bowel Diseases: A Pilot Study. Life (Basel) 2024; 14:1226. [PMID: 39459526 PMCID: PMC11509059 DOI: 10.3390/life14101226] [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: 08/26/2024] [Revised: 09/14/2024] [Accepted: 09/24/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is characterized by persistent inflammation and is often associated with metabolic dysfunction-associated steatotic liver disease (MASLD). IBD patients are at risk of developing MASLD due to shared risk factors such as gut dysbiosis and systemic inflammation. The new MASLD nomenclature emphasizes the link between liver steatosis and cardiometabolic comorbidities. However, the prevalence of MASLD in IBD patients remains poorly explored. The main aim of this cross-sectional study is to assess the prevalence of ultrasound (US) and the clinical features of MASLD in patients with IBDs. MATERIALS AND METHODS We conducted a retrospective study enrolling 272 Italian IBD patients attending Renato Dulbecco Teaching Hospital in a period between 1 January 2021 and 31 December 2023. MASLD was diagnosed based on the presence of liver steatosis with cardiometabolic risk factors, using established guidelines. Demographic, clinical, and laboratory data were collected and analyzed. Statistical significance was determined at a p-value < 0.05. RESULTS Of the 272 IBD patients, 6% had non-alcoholic fatty liver disease (NAFLD), while 18% had MASLD. Patients with IBD-MASLD were significantly older, had higher body mass index, waist circumference, and triglyceride levels, and were more likely to have type 2 diabetes mellitus and hypertension compared to those with IBD-NAFLD. IBD-MASLD patients also showed higher disease activity scores and required more frequent surgical interventions. Bivariate logistic regression revealed triglyceride levels as a significant predictor of MASLD in IBD patients. CONCLUSIONS MASLD is more prevalent in IBD patients, highlighting the importance of early detection of liver steatosis in this at-risk population. The association between MASLD and cardiometabolic risk factors underscores the need for a multidisciplinary approach to manage these patients effectively. Further studies in larger cohorts are necessary to confirm these findings and explore the pathophysiological mechanisms involved.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (R.S.); (G.G.M.S.); (M.L.G.); (F.L.)
| | - Rocco Spagnuolo
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (R.S.); (G.G.M.S.); (M.L.G.); (F.L.)
| | - Giuseppe Guido Maria Scarlata
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (R.S.); (G.G.M.S.); (M.L.G.); (F.L.)
| | - Maria Luisa Gambardella
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (R.S.); (G.G.M.S.); (M.L.G.); (F.L.)
| | - Luigi Boccuto
- Healthcare Genetics and Genomics Doctoral Program, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29634, USA;
| | - Nahum Méndez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico;
| | - Francesco Luzza
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (R.S.); (G.G.M.S.); (M.L.G.); (F.L.)
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Donghia R, Tatoli R, Campanella A, Losurdo G, Di Leo A, De Pergola G, Bonfiglio C, Giannelli G. Extra Virgin Olive Oil Reduces the Risk of Non-Alcoholic Fatty Liver Disease in Females but Not in Males: Results from the NUTRIHEP Cohort. Nutrients 2024; 16:3234. [PMID: 39408202 PMCID: PMC11478343 DOI: 10.3390/nu16193234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. One way to resolve this reversible condition is by making dietary changes. Extra virgin olive oil (EVOO) is often associated with an improvement in this disease. The aim of this study was to explore the protective role of EVOO on NAFLD conditions, stratified by gender. METHODS The study cohort included 1426 participants assessed in the second recall of the NUTRIHEP cohort (2014-2018), subdivided by gender and dividing the EVOO intake into quartiles of daily gram intake. RESULTS The results indicated a protective role of the last quartile of EVOO only for female subjects, OR = 0.43, p = 0.02, 0.21 to 0.85 at 95% C.I., whereas in the male sub-cohort, the effect was not statistically significant. CONCLUSIONS The protective role of EVOO is different between genders. This difference has not been explored in the literature, so we conclude that this is one of the few papers in the literature to evaluate a gender difference in the intestinal absorption of humans based on an epidemiological study.
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Affiliation(s)
- Rossella Donghia
- National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (R.T.); (A.C.); (G.D.P.); (C.B.); (G.G.)
| | - Rossella Tatoli
- National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (R.T.); (A.C.); (G.D.P.); (C.B.); (G.G.)
| | - Angelo Campanella
- National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (R.T.); (A.C.); (G.D.P.); (C.B.); (G.G.)
| | - Giuseppe Losurdo
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy; (G.L.); (A.D.L.)
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy; (G.L.); (A.D.L.)
| | - Giovanni De Pergola
- National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (R.T.); (A.C.); (G.D.P.); (C.B.); (G.G.)
| | - Caterina Bonfiglio
- National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (R.T.); (A.C.); (G.D.P.); (C.B.); (G.G.)
| | - Gianluigi Giannelli
- National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (R.T.); (A.C.); (G.D.P.); (C.B.); (G.G.)
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Oh J, Kim BK, Yoon JH, Lee HH, Park H, Lee J, Park Y, Yun B, Chung J. Metabolic Dysfunction-Associated Steatotic Liver Disease Is Associated with Increased Risk of Kidney Cancer: A Nationwide Study. Cancers (Basel) 2024; 16:3161. [PMID: 39335133 PMCID: PMC11430135 DOI: 10.3390/cancers16183161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/13/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Background: This study investigated the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and Kidney Cancer Risk, as the incidence of both diseases gradually increases owing to metabolic health issues. Methods: Participants (aged 20-79) undergoing a national health examination between 2009 and 2010 were monitored for new-onset kidney cancer. The MASLD spectrum was classified as non-MASLD, MASLD, or MASLD with increased alcohol uptake (MetALD). Kidney Cancer Risk associated with the MASLD spectrum was estimated using multivariate Cox proportional hazard models. Age- and sex-stratified analyses were also performed. Results: Among 8,829,510 participants (median follow-up 13.3 years), the proportion of non-MASLD, MASLD, and MetALD was 64.9%, 30.3%, and 4.7%, respectively, with newly developed kidney cancer in 17,555 participants. Kidney cancer was significantly increased with MASLD (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.46-1.56) and MetALD (aHR 1.51, 95% CI 1.42-1.61), compared with the non-MASLD group. Kidney Cancer Risk was the highest among young populations (aHR 1.93, 95% CI 1.77-2.11 for MASLD and aHR 1.91, 95% CI 1.65-2.22 for MetALD), according to stratification analysis. Furthermore, the cumulative relationship between metabolic dysfunction and Kidney Cancer Risk was confirmed across all MASLD spectra. Conclusions: Our study highlights the positive association between MASLD and Kidney Cancer Risk, emphasizing a comprehensive approach to metabolic health. This also serves as a call to devote closer attention to the metabolic health of younger patients.
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Affiliation(s)
- Juyeon Oh
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Republic of Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul 03722, Republic of Korea
| | - Hyung Ho Lee
- Department of Urology, National Cancer Center, Goyang 10408, Republic of Korea
| | - Heejoo Park
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
| | - Jian Lee
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
| | - Youngsun Park
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
| | - Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul 03722, Republic of Korea
| | - Jinsoo Chung
- Department of Urology, National Cancer Center, Goyang 10408, Republic of Korea
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Uojima H, Tsujikawa H, Yamazaki K, Sugiyama M, Take A, Sakaguchi Y, Gotoh K, Satoh T, Hidaka H, Hayashi S, Kusano C, Sakamoto M, Mizokami M. Hepatic Mac2-BP expression depends on liver fibrosis and inflammation due to fat accumulation in patients with metabolic dysfunction-associated steatotic liver disease. Hepatol Res 2024. [PMID: 39257093 DOI: 10.1111/hepr.14109] [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: 06/08/2024] [Revised: 07/30/2024] [Accepted: 08/16/2024] [Indexed: 09/12/2024]
Abstract
AIM Data on the upregulation of Mac-2 binding protein (M2BP) expression associated with fat accumulation in the liver are limited. Therefore, we aimed to assess the relationship between hepatic M2BP expression and changes in the liver microenvironment due to fat accumulation in patients with metabolic dysfunction associated steatotic liver disease (MASLD). METHODS Liver specimens obtained from 46 patients with MASLD were subjected to immunohistochemical staining to visualize M2BP expression in the liver. The staining intensity in the hepatocytes and sinusoidal cells was classified as high or low grade. First, the correlation between hepatic M2BP expression and microenvironmental changes caused by fat accumulation was examined. Then, the influence of hepatic M2BP expression on serum M2BP glycosylation isomer levels in patients with MASLD was evaluated. RESULTS The staining grade of M2BP was higher in the sinusoidal cells than in the hepatocytes (p = 0.015). The patients with high staining grade in their hepatocytes had more severe lobular inflammation than those with low staining grade (p = 0.037). Additionally, the patients with high staining grade in their sinusoidal cells presented more severe fibrosis than those with low staining grade (p = 0.018). The staining grade in the hepatocytes correlated positively with serum M2BP glycosylation isomer levels (p = 0.023), whereas no correlation was observed between sinusoidal staining grade and serum M2BP glycosylation isomer levels (p = 0.393). CONCLUSIONS Fat accumulation in patients with MASLD leads to M2BP expression in hepatocytes due to liver inflammation and that in sinusoidal cells due to fibrosis.
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Affiliation(s)
- Haruki Uojima
- Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hanako Tsujikawa
- Department of Diagnostic Pathology, National Hospital Organization Saitama Hospital, Wako, Japan
- Department of Pathology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
| | - Ken Yamazaki
- Department of Pathology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
- Division of Molecular Pathology, Research Institute, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan
| | - Masaya Sugiyama
- Department of Viral Pathogenesis and Controls, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Akira Take
- Department of Microbiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Yoshihiko Sakaguchi
- Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, Japan
| | - Kazuyoshi Gotoh
- Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Takashi Satoh
- Division of Hematology, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Shunji Hayashi
- Department of Viral Pathogenesis and Controls, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Chika Kusano
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
- Department of Pathology, School of Medicine, International University of Health and Welfare, Narita, Chiba, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
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Rakusanova S, Cajka T. Metabolomics and Lipidomics for Studying Metabolic Syndrome: Insights into Cardiovascular Diseases, Type 1 & 2 Diabetes, and Metabolic Dysfunction-Associated Steatotic Liver Disease. Physiol Res 2024; 73:S165-S183. [PMID: 39212142 PMCID: PMC11412346 DOI: 10.33549/physiolres.935443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
Metabolomics and lipidomics have emerged as tools in understanding the connections of metabolic syndrome (MetS) with cardiovascular diseases (CVD), type 1 and type 2 diabetes (T1D, T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review highlights the applications of these omics approaches in large-scale cohort studies, emphasizing their role in biomarker discovery and disease prediction. Integrating metabolomics and lipidomics has significantly advanced our understanding of MetS pathology by identifying unique metabolic signatures associated with disease progression. However, challenges such as standardizing analytical workflows, data interpretation, and biomarker validation remain critical for translating research findings into clinical practice. Future research should focus on optimizing these methodologies to enhance their clinical utility and address the global burden of MetS-related diseases.
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Affiliation(s)
- S Rakusanova
- Laboratory of Translational Metabolism, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
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Ciardullo S, Perseghin G. From NAFLD to MAFLD and MASLD: a tale of alcohol, stigma and metabolic dysfunction. METABOLISM AND TARGET ORGAN DAMAGE 2024. [DOI: 10.20517/mtod.2024.39] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Liver steatosis is a frequent finding in clinical practice and it is estimated to affect 30% of the general adult population worldwide. It became one of the leading causes of end-stage liver disease and hepatocellular carcinoma. From its first description, a diagnosis of nonalcoholic fatty liver disease (NAFLD) required the exclusion of excessive alcohol consumption and concomitant chronic liver diseases of different origins, making it a diagnosis of exclusion. In recent years, the need to stress the strict association between liver steatosis and metabolic dysfunction (i.e., insulin resistance, overweight/obesity, type 2 diabetes, and metabolic syndrome), as well as the desire to define a condition in a positive rather than negative way, led to new definitions and new diagnostic criteria. Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by Eslam et al. in 2020. More recently, a Delphi consensus endorsed by several international hepatologic societies proposed a new terminology [metabolic dysfunction-associated steatotic liver disease (MASLD)] and a new set of diagnostic criteria. The MAFLD and MASLD definitions have a good degree of concordance. They mainly differ in the number of metabolic derangements needed to define “metabolic dysfunction” in normal-weight individuals and in alcohol consumption. Indeed, while MAFLD does not exclude patients with significant alcohol consumption, the recent Delphi consensus included the metabolic dysfunction and alcohol-related liver disease (MetALD) disease entity, a condition in which steatosis, metabolic dysfunction, and moderate alcohol intake coexist. In the present narrative review, we underline the strengths and possible limitations of each definition and summarize available evidence from epidemiologic studies evaluating the clinical usefulness of each set of diagnostic criteria.
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Zou J, Li J, Wang X, Tang D, Chen R. Neuroimmune modulation in liver pathophysiology. J Neuroinflammation 2024; 21:188. [PMID: 39090741 PMCID: PMC11295927 DOI: 10.1186/s12974-024-03181-w] [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: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 08/04/2024] Open
Abstract
The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area.
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Affiliation(s)
- Ju Zou
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jie Li
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoxu Wang
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Ruochan Chen
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Zhu Y, Wang L, Lin L, Huo Y, Wan Q, Qin Y, Hu R, Shi L, Su Q, Yu X, Yan L, Qin G, Tang X, Chen G, Wang S, Lin H, Wu X, Hu C, Li M, Xu M, Xu Y, Wang T, Zhao Z, Gao Z, Wang G, Shen F, Gu X, Luo Z, Chen L, Li Q, Ye Z, Zhang Y, Liu C, Wang Y, Wu S, Yang T, Deng H, Chen L, Zeng T, Zhao J, Mu Y, Wang W, Ning G, Bi Y, Chen Y, Lu J. The Association between Educational Attainment and the Risk of Nonalcoholic Fatty Liver Disease among Chinese Adults: Findings from the REACTION Study. Gut Liver 2024; 18:719-728. [PMID: 38384199 PMCID: PMC11249937 DOI: 10.5009/gnl230220] [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: 06/13/2023] [Revised: 09/14/2023] [Accepted: 09/21/2023] [Indexed: 02/23/2024] Open
Abstract
Background/Aims : Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.
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Affiliation(s)
- Yuanyue Zhu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Long Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lin Lin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanan Huo
- Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, China
| | - Qin Wan
- The Affiliated Hospital of Luzhou Medical College, Luzhou, China
| | - Yingfen Qin
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ruying Hu
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Lixin Shi
- Affiliated Hospital of Guiyang Medical University, Guiyang, China
| | - Qing Su
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuefeng Yu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Yan
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guijun Qin
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xulei Tang
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Gang Chen
- Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China
| | - Shuangyuan Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Lin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xueyan Wu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chunyan Hu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhengnan Gao
- Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, China
| | - Guixia Wang
- The First Hospital of Jilin University, Changchun, China
| | - Feixia Shen
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xuejiang Gu
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zuojie Luo
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Li Chen
- Qilu Hospital of Shandong University, Jinan, China
| | - Qiang Li
- The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhen Ye
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Yinfei Zhang
- Central Hospital of Shanghai Jiading District, Shanghai, China
| | - Chao Liu
- Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China
| | - Youmin Wang
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Shengli Wu
- Karamay Municipal People’s Hospital, Xinjiang, China
| | - Tao Yang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Huacong Deng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lulu Chen
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tianshu Zeng
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiajun Zhao
- Shandong Provincial Hospital affiliated to Shandong University, Jinan, and
| | - Yiming Mu
- Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Nazir S, Abbas Z, Gazder DP, Maqbool S, Samejo SA, Kumar M. Characterizing Nonalcoholic Fatty Liver Disease (NAFLD) in Lean Individuals at a Tertiary Care Hospital: A Cross-sectional Study. Euroasian J Hepatogastroenterol 2024; 14:198-204. [PMID: 39802861 PMCID: PMC11714105 DOI: 10.5005/jp-journals-10018-1452] [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: 09/22/2024] [Accepted: 10/14/2024] [Indexed: 01/16/2025] Open
Abstract
Background Fat accumulation in the liver is affecting 38% of the global population. It can also occur in normal-weight individuals, termed lean non-alcoholic fatty liver disease (NAFLD). This study examines Asian and Western body mass index (BMI) criteria, as well as metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) diagnostic guidelines, in lean fatty liver cases within a healthcare setting. Materials and methods This study was cross-sectional included 111 lean patients diagnosed with NAFLD using either ultrasound or VCTE from January 2023 to March 2024. Anthropometric, laboratory and non-invasive liver fibrosis evaluation parameters were used. The study assessed clinical characteristics and metabolic risk factors of patients with BMI ≤ 23 kg/m2 and BMI between 23 and ≤ 25 kg/m2 using MASLD and MAFLD diagnostic criteria. Results The cohort included NAFLD patients with a mean age of 43.3 years (±13.2 years). Of the participants, 33% were diagnosed through ultrasonography, whereas 67% diagnosis were made via Fibro scan. Majority were male 92 (83%), while females were 19 (17%) of the entire group. The lean NAFLD criteria for Asia and the West were satisfied by 43 (39%) persons with a BMI ≤ 23 kg/m2 and 68 (61%) individuals with a BMI between 23 and ≤ 25 kg/m2, respectively. The average body mass index (BMI) was 23.0 ± 1.5 kg/m2. Diabetes was observed in 16%, hypertension 11%, and ischemic heart disease in 2%. Out of the total individuals, 92 satisfied the MASLD-MAFLD criteria, whereas 18 did not qualify the MAFLD criteria for diagnosis and were classed as MASLD-Alone. Elevated triglycerides, insulin resistance (HOMA-IR ≥ 2), and three or more cardiometabolic risk factors (CMRF) were significant in the MASLD-MAFLD group compared to the MASLD-Alone group (p < 0.05). Comparing BMI criteria, no significant differences were found in terms of fibrosis between the Western and Asian lean NAFLD BMI criteria's (p = 0.243). Conclusion Lean NAFLD is a major global health concern. Applying non-Asian BMI criteria (BMI ≤ 25 kg/m2) for lean Asians improves early detection and intervention for at-risk individuals. Accurate use of MAFLD and MASLD criteria is essential to prevent confusion in diagnosing lean NAFLD. Further multicenter investigations with larger sample numbers are required to corroborate these results in our community. How to cite this article Nazir S, Abbas Z, Gazder DP, et al. Characterizing Nonalcoholic Fatty Liver Disease (NAFLD) in Lean Individuals at a Tertiary Care Hospital: A Cross-sectional Study. Euroasian J Hepato-Gastroenterol 2024;14(2):198-204.
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Affiliation(s)
- Shamim Nazir
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Zaigham Abbas
- Department of Gastroenterology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Darayus P Gazder
- Department of Gastroenterology and Hepatology, Dr. Ziauddin University Hospital, Karachi, Pakistan
| | - Sania Maqbool
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Shaukat Ali Samejo
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Manesh Kumar
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
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Jamalinia M, Lonardo A. Perspective article: determinants and assessment of cardiovascular risk in steatotic liver disease owing to metabolic dysfunction-addressing the challenge. METABOLISM AND TARGET ORGAN DAMAGE 2024; 4. [DOI: 10.20517/mtod.2024.34] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) stands as an independent risk factor for cardiovascular disease (CVD), which is the leading cause of mortality among MASLD patients. The diverse spectrum of cardio-nephro-metabolic and vascular manifestations inherent in MASLD highlights the complex profile of CVD risk associated with this condition. However, current approaches to assessing CVD risk in MASLD lack specificity, predominantly relying on traditional markers. Although it is widely accepted that patients with advanced fibrosis are more prone to CVD risk, recent evidence suggests that this isolated focus may overlook the remarkable phenotypic variability of this CVD risk across the entire MASLD population. Emerging data indicate a progressive escalation of CVD risk in parallel with the severity of MASLD, highlighting the need for precise disease staging to inform accurate risk assessment. To address this challenge, we propose a novel sequential approach to CVD risk assessment in MASLD. While traditional CVD risk factors remain essential, incorporating liver-specific parameters enhances risk stratification and guides targeted interventions to mitigate the substantial burden of cardiovascular disease in this vulnerable population. This approach involves initial screening using FIB-4 and NAFLD fibrosis score, followed by assessment of liver fibrosis with imaging-based non-invasive techniques in individuals at intermediate-high risk for advanced fibrosis and liver fat quantification in low-risk individuals. Future prospective investigations should focus on the simultaneous use of liver biomarkers and imaging modalities to evaluate, in a sex-specific manner, the efficacy of the proposed approach and to determine optimal thresholds of liver fibrosis and steatosis for optimal CVD risk assessment.
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Suzuki K, Tamaki N, Kurosaki M, Takahashi Y, Yamazaki Y, Uchihara N, Tanaka Y, Miyamoto H, Yamada M, Keitoku T, Okada R, Higuchi M, Takaura K, Tanaka S, Maeyashiki C, Yasui Y, Tsuchiya K, Nakanishi H, Izumi N. Concordance between metabolic dysfunction-associated steatotic liver disease and nonalcoholic fatty liver disease. Hepatol Res 2024; 54:600-605. [PMID: 38234088 DOI: 10.1111/hepr.14011] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/18/2023] [Accepted: 12/31/2023] [Indexed: 01/19/2024]
Abstract
AIM A multisociety consensus group proposed a new nomenclature for metabolic dysfunction-associated steatotic liver disease (MASLD). Although patients with nonalcoholic fatty liver disease (NAFLD) are expected to be reclassified as patients with MASLD under the new nomenclature, the concordance between MASLD and NAFLD remains unclear. Moreover, waist circumference could be adjusted by ethnicity for diagnosing MASLD; however, there are limited data on the optimal waist circumference in the Japanese population. METHODS This cross-sectional study was conducted on 3709 Japanese patients with NAFLD. The primary endpoint was the prevalence of MASLD in patients with NAFLD. The difference between the original waist circumference criteria (>94 cm for men and >80 cm for women) and the Japanese metabolic syndrome criteria (≥85 cm for men and ≥90 cm for women) for concordance between NAFLD and MASLD was also investigated. RESULTS According to the original criteria, the prevalence of MASLD in patients with NAFLD was 96.7%. Similarly, according to the Japanese waist circumference criteria, 96.2% of patients with NAFLD could be reclassified as those with MASLD. The concordance rate was significantly higher in the original criteria than in the Japanese criteria (p = 0.02). CONCLUSIONS NAFLD could be considered MASLD using the original MASLD criteria in the Japanese population, and insights from NAFLD research could be applied to MASLD.
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Affiliation(s)
- Keito Suzuki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yudai Yamazaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Naoki Uchihara
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuki Tanaka
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Haruka Miyamoto
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michiko Yamada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Taisei Keitoku
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Risa Okada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shohei Tanaka
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Chrysavgis L, Cholongitas E. From NAFLD to MASLD: what does it mean? Expert Rev Gastroenterol Hepatol 2024; 18:217-221. [PMID: 38934451 DOI: 10.1080/17474124.2024.2374472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 06/26/2024] [Indexed: 06/28/2024]
Affiliation(s)
- Lampros Chrysavgis
- First Department of Internal Medicine, Athens Naval Hospital, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens Greece
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Boldys A, Buldak L. Metabolic dysfunction-associated steatotic liver disease: Navigating terminological evolution, diagnostic frontiers and therapeutic horizon-an editorial exploration. World J Gastroenterol 2024; 30:2387-2390. [PMID: 38764762 PMCID: PMC11099391 DOI: 10.3748/wjg.v30.i18.2387] [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: 12/28/2023] [Revised: 04/07/2024] [Accepted: 04/24/2024] [Indexed: 05/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), once known as non-alcoholic fatty liver disease (NAFLD), represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes. The redefinition of NAFLD in 2023 marked a significant reposition in terminology, emphasizing a broader understanding of liver steatosis and its associated risks. MASLD is now recognized as a major risk factor for liver cirrhosis, hepatocellular carcinoma, and systemic complications such as cardiovascular diseases or systemic inflammation. Diagnostic challenges arise, particularly in identifying MASLD in lean individuals, necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools. Therapeutically, there is an urgent need for effective treatments targeting MASLD, with emerging pharmacological options focusing on, among others, carbohydrate and lipid metabolism. Additionally, understanding the roles of bile acid metabolism, the microbiome, and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches. There is a strong need to emphasize the importance of collaborative efforts in understanding, diagnosing, and managing MASLD to improve physicians' approaches and patient outcomes.
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Affiliation(s)
- Aleksandra Boldys
- Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice 40-752, Poland
| | - Lukasz Buldak
- Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice 40-752, Poland
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Pavlov CS, Teplyuk DA, Lazebnik LB, Ametov AS, Pashkova EY, Sorokoletov SM, Uspenskiy YP, Turkina SV, Ponomarenko EV, Maslakov AS. The clinician's view on the advantages and contradictions of the new nomenclature of steatotic liver disease: A review. TERAPEVT ARKH 2024; 96:429-435. [DOI: 10.26442/00403660.2024.04.202747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
In September 2023, the European Association for the Study of the Liver (EASL) updated the disease nomenclature for non-alcoholic (metabolically associated) fatty liver disease. The goals of the revision were to increase awareness among health care professionals, civil society and patients about the disease, its course, treatment and outcomes; combating stigma; focusing on the initial etiological factor, including the main (cardiometabolic) risk of disease progression; improved diagnosis based on disease biomarkers; positive impact on the potency to search for new drugs; the ability to provide personalized medical care. The terms “non-alcoholic” and “fatty” were considered stigmatizing, and therefore, it was proposed to use the term steatotic liver disease (SLD) as the name of this nosology. The terms non-alcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD) have been replaced by the term metabolic dysfunction-associated steatotic liver disease (MASLD). In the case of being combined with an alcohol factor, a diagnosis in which metabolic dysfunction is combined with alcoholic liver disease is referred to as MetALD. The fundamental principle in the diagnosis of MASLD is the presence of at least one of the cardiometabolic risk factors. Alcohol consumption interacts with cardiometabolic risk factors and increases the risk of SLD decompensation. The term nonalcoholic steatohepatitis (NASH), according to the new nomenclature, has been replaced by the term metabolic dysfunction-associated steatohepatitis (MASH). The adoption of the new nomenclature should help to increase awareness about the disease, its course and outcomes, as well as improve the quality of diagnosis and treatment.
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Affiliation(s)
- Chavdar S. Pavlov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - Daria A. Teplyuk
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | - Evgeniia Yu. Pashkova
- Russian Medical Academy of Continuous Professional Education
- Botkin City Clinical Hospital
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Kountouras J, Boziki M, Kazakos E, Theotokis P, Kesidou E, Nella M, Bakirtzis C, Karafoulidou E, Vardaka E, Mouratidou MC, Kyrailidi F, Tzitiridou-Chatzopoulou M, Orovou E, Giartza-Taxidou E, Deretzi G, Grigoriadis N, Doulberis M. Impact of Helicobacter pylori and metabolic syndrome on mast cell activation-related pathophysiology and neurodegeneration. Neurochem Int 2024; 175:105724. [PMID: 38508416 DOI: 10.1016/j.neuint.2024.105724] [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: 12/08/2023] [Revised: 03/03/2024] [Accepted: 03/17/2024] [Indexed: 03/22/2024]
Abstract
Both Helicobacter pylori (H. pylori) infection and metabolic syndrome (MetS) are highly prevalent worldwide. The emergence of relevant research suggesting a pathogenic linkage between H. pylori infection and MetS-related cardio-cerebrovascular diseases and neurodegenerative disorders, particularly through mechanisms involving brain pericyte deficiency, hyperhomocysteinemia, hyperfibrinogenemia, elevated lipoprotein-a, galectin-3 overexpression, atrial fibrillation, and gut dysbiosis, has raised stimulating questions regarding their pathophysiology and its translational implications for clinicians. An additional stimulating aspect refers to H. pylori and MetS-related activation of innate immune cells, mast cells (MC), which is an important, often early, event in systemic inflammatory pathologies and related brain disorders. Synoptically, MC degranulation may play a role in the pathogenesis of H. pylori and MetS-related obesity, adipokine effects, dyslipidemia, diabetes mellitus, insulin resistance, arterial hypertension, vascular dysfunction and arterial stiffness, an early indicator of atherosclerosis associated with cardio-cerebrovascular and neurodegenerative disorders. Meningeal MC can be activated by triggers including stress and toxins resulting in vascular changes and neurodegeneration. Likewise, H.pylori and MetS-related MC activation is linked with: (a) vasculitis and thromboembolic events that increase the risk of cardio-cerebrovascular and neurodegenerative disorders, and (b) gut dysbiosis-associated neurodegeneration, whereas modulation of gut microbiota and MC activation may promote neuroprotection. This narrative review investigates the intricate relationship between H. pylori infection, MetS, MC activation, and their collective impact on pathophysiological processes linked to neurodegeneration. Through a comprehensive search of current literature, we elucidate the mechanisms through which H. pylori and MetS contribute to MC activation, subsequently triggering cascades of inflammatory responses. This highlights the role of MC as key mediators in the pathogenesis of cardio-cerebrovascular and neurodegenerative disorders, emphasizing their involvement in neuroinflammation, vascular dysfunction and, ultimately, neuronal damage. Although further research is warranted, we provide a novel perspective on the pathophysiology and management of brain disorders by exploring potential therapeutic strategies targeting H. pylori eradication, MetS management, and modulation of MC to mitigate neurodegeneration risk while promoting neuroprotection.
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Affiliation(s)
- Jannis Kountouras
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece.
| | - Marina Boziki
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Evangelos Kazakos
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece; School of Healthcare Sciences, Midwifery Department, University of West Macedonia, Koila, Kozani, 50100, Macedonia, Greece
| | - Paschalis Theotokis
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Evangelia Kesidou
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Maria Nella
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Christos Bakirtzis
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Eleni Karafoulidou
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Elisabeth Vardaka
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece; Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, Alexander Campus, 57400, Macedonia, Greece
| | - Maria C Mouratidou
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece
| | - Foteini Kyrailidi
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece
| | - Maria Tzitiridou-Chatzopoulou
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece; School of Healthcare Sciences, Midwifery Department, University of West Macedonia, Koila, Kozani, 50100, Macedonia, Greece
| | - Eirini Orovou
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece; School of Healthcare Sciences, Midwifery Department, University of West Macedonia, Koila, Kozani, 50100, Macedonia, Greece
| | - Evaggelia Giartza-Taxidou
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece
| | - Georgia Deretzi
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece; Department of Neurology, Papageorgiou General Hospital, Thessaloniki, Macedonia, Greece
| | - Nikolaos Grigoriadis
- Laboratory of Experimental Neurology and Neuroimmunology and the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Michael Doulberis
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642, Thessaloniki, Macedonia, Greece; Gastroklinik, Private Gastroenterological Practice, 8810, Horgen, Switzerland; Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001, Aarau, Switzerland
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