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Balakrishnan S, Ranganathan P, Prabhudesai KS, Vijay R, Gawali VP, Kareenhalli V. MASLD Risk Score (MRS) and Random Forest model (RF Model): Novel tools for screening and severity assessment of MASLD. Comput Biol Med 2025; 192:110314. [PMID: 40328026 DOI: 10.1016/j.compbiomed.2025.110314] [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: 12/06/2024] [Revised: 04/21/2025] [Accepted: 04/30/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND AND AIMS Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) spans from simple steatosis to progressive forms like non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis, making early diagnosis and grading crucial. This study aimed to develop and validate predictive models for diagnosing and assessing MASLD severity using routinely available biomarkers from both public and clinical datasets. APPROACH & RESULTS We developed a novel MASLD Risk Score (MRS) using data from the CDC NHANES (2000-2020) and validated it in a clinically profiled Indian cohort. Unlike existing indices, the predictors were derived through data-driven feature selection from large dataset, ensuring statistical robustness. It integrates novel (Uric Acid, HOMA-IR) and established (liver enzymes, triglycerides, waist circumference, BMI) biomarkers to improve metabolic profiling and predictive accuracy. The MRS also uniquely enables grading of MASLD severity, addressing a key limitation of previous models. The MRS achieved AUROCs of 0.91 (public) and 0.85 (clinical) with accuracies of 94 % and 82 %, respectively. A Random Forest (RF) model built on the same features provided AUROCs of 0.87 (public) and 0.94 (clinical), with accuracies of 83 % and 82 %. MRS parameters were optimized using a diverse population, improving generalizability across demographics. Both models showed strong correlation with ultrasonography results and outperformed existing indices. CONCLUSIONS The MRS offers a novel, interpretable, and cost-effective solution for MASLD screening. Its development from a large, demographically diverse population and incorporation of varied biomarkers supports generalizability. While results are promising, external validation in multi-center clinical settings is needed to confirm broad utility.
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Affiliation(s)
| | | | | | - Ria Vijay
- Bhaktivedanta Hospital and Research Institute, India
| | | | - Venkatesh Kareenhalli
- MetFlux Research Private Limited, India; Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India.
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Wang B, Li Y, Ouyang Q, Xu MT, Wang YY, Fu SJ, Liu WQ, Liu XT, Ling H, Zhang X, Xiu RJ, Liu MM. Strain- and sex-dependent variability in hepatic microcirculation and liver function in mice. World J Gastroenterol 2025; 31:101058. [PMID: 40309233 PMCID: PMC12038547 DOI: 10.3748/wjg.v31.i15.101058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 02/02/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND The integrity and functionality of the hepatic microcirculation are essential for maintaining liver health, which is influenced by sex and genetic background. Understanding these variations is crucial for addressing disparities in liver disease outcomes. AIM To investigate the sexual dimorphism and genetic heterogeneity of liver microcirculatory function in mice. METHODS We assessed hepatic microhemodynamics in BALB/c, C57BL/6J, and KM mouse strains using laser Doppler flowmetry and wavelet analysis. We analyzed the serum levels of alanine transaminase, glutamic acid aminotransferase, total bile acid, total protein, alkaline phosphatase, and glucose. Histological and immunohistochemical staining were employed to quantify microvascular density and the expression levels of cluster of differentiation (CD) 31, and estrogen receptor α, and β. Statistical analyses, including the Mantel test and Pearson correlation, were conducted to determine the relationships among hepatic function, microcirculation, and marcocirculation between different sexes and across genetic backgrounds. RESULTS We identified sex-based disparities in hepatic microhemodynamics across all strains, with males exhibiting higher microvascular perfusion and erythrocyte concentration, but lower blood velocity. Strain-specific differences were evident, particularly in the endothelial oscillatory characteristics of the erythrocyte concentration. No sex-dependent differences in estrogen receptor expression were observed, while significant variations in CD31 expression and microvascular density were observed. The correlations highlighted relationships between hepatic microhemodynamics and liver function indicators. CONCLUSION Our findings indicate the influence of genetic and sex differences on hepatic microcirculation and liver function, highlighting the necessity of incorporating both genetic background and sex into hepatic physiology studies and potential liver disease management strategies.
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Affiliation(s)
- Bing Wang
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Yuan Li
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Qin Ouyang
- Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Science, Beijing 100102, China
| | - Meng-Ting Xu
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Ying-Yu Wang
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Sun-Jing Fu
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Wei-Qi Liu
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Xue-Ting Liu
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Hao Ling
- Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, Hunan Province, China
| | - Xu Zhang
- Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing 100034, China
| | - Rui-Juan Xiu
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Ming-Ming Liu
- Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
- Diabetes Research Center, Chinese Academy of Medical Sciences, Beijing 100005, China
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Miller KC, Geyer B, Alexopoulos AS, Moylan CA, Pagidipati N. Disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease Prevalence, Diagnosis, Treatment, and Outcomes: A Narrative Review. Dig Dis Sci 2025; 70:154-167. [PMID: 39560808 DOI: 10.1007/s10620-024-08722-0] [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: 12/19/2023] [Accepted: 10/26/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a leading cause of morbidity and mortality, and health disparities have been shown to influence disease burden. AIM In this review, we aim to characterize disparities in prevalence, diagnosis, treatment, and outcomes of MASLD, and to make recommendations for next steps to minimize these disparities. METHODS Literature search on PubMed and Scopus databases was conducted to identify relevant articles published before September 2, 2024. RESULTS Relative to women and White populations, MASLD is more common in men and Hispanic populations and less common in Black populations. It is also more prevalent among those with lower SES. Noninvasive clinical scores may perform differently across groups, and screening practices vary both for initial disease and for progression to metabolic dysfunctionassociated steatohepatitis (MASH), formerly called non-alcoholic steatohepatitis (NASH). Women and Black and Hispanic patients suffer worse outcomes including rates of progression to MASH and mortality. CONCLUSIONS Health disparities related to race, ethnicity, gender, and socioeconomic factors impact multiple stages of care for patients with MASLD.
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Errico J. Metabolic syndrome: Understanding its root cause, and the role of macrophages and why vagus nerve stimulation may be an effective treatment. VAGUS NERVE STIMULATION 2025:313-325. [DOI: 10.1016/b978-0-12-816996-4.00014-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Hu J, Du Y, Zhou Y, Wang H. High sensitivity troponins and mortality in the population with metabolic dysfunction-associated steatotic liver disease. Sci Rep 2024; 14:19541. [PMID: 39174636 PMCID: PMC11341865 DOI: 10.1038/s41598-024-70645-7] [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: 04/29/2024] [Accepted: 08/20/2024] [Indexed: 08/24/2024] Open
Abstract
Given the global high prevalence of MASLD and its poor CVD prognosis, it is essential to perform risk stratification for MASLD patients. The specific impact of High Sensitivity Troponins (hs-cTn ) on mortality in MASLD patients remains unexplored. The NHANES databases from 1999 to 2004, which include data on high-sensitivity cardiac troponin (hs-cTn) levels and comorbidities, were linked with the most recent mortality dataset. Myocardial injury was determined using the 99th upper reference limits (URL) for hs-cTn. Our study included 3460 MASLD patients. The mean follow-up duration was 192 months, during which 1074 (23%) MASLD participants died from all-cause mortality, and 363 (7.3%) died from CVD mortality. Our findings indicate that MASLD patients with elevated levels of hs-cTnT (> 99th URL) exhibit increased risks of all-cause mortality [adjusted hazard ratio (aHR) = 1.93] and CVD mortality (aHR = 2.4). Similar results were observed for hs-cTnI, where the aHRs for all-cause mortality and CVD mortality were 2.03 and 2.97, respectively. Furthermore, we identified a nonlinear dose-response relationship between hs-cTn levels and the risk of mortality (P for nonlinearity < 0.001). Our findings suggest that hs-cTn can predict mortality risk in MASLD, aiding clinicians in risk-stratifying this population. Therefore, we recommend considering hs-cTn detection in individuals with MASLD to effectively assess their future mortality risk.
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Affiliation(s)
- Jingjing Hu
- Department of Emergency Medicine, Hangzhou Third People's Hospital, Hangzhou, China
| | - Yuteng Du
- Department of Emergency Medicine, Hangzhou Third People's Hospital, Hangzhou, China
- Department of Allergy and Clinical Immunology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yidan Zhou
- Department of Emergency Medicine, Hangzhou Third People's Hospital, Hangzhou, China.
| | - Huiying Wang
- Department of Allergy and Clinical Immunology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Wen Y, Weng P, Li Y, Yang L, Li C, Chen Q, He Y, Zhang W, Hu H, Yuan Z, Yu C. Triglyceride-Targeted Molecularly Imprinted Polymers Activate Lipophagy via Cargo Exchange for Nonalcoholic Fatty Liver Disease Treatment. ACS APPLIED POLYMER MATERIALS 2024; 6:7265-7277. [DOI: 10.1021/acsapm.4c01222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Affiliation(s)
- Yilin Wen
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Ping Weng
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Yueyue Li
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Liming Yang
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Chengju Li
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Qingyang Chen
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Yanni He
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Wanping Zhang
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Hui Hu
- Pharmaceutical and Nanomedicine Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Zhiyi Yuan
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
| | - Chao Yu
- Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
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Zhou Q, Hu H, Hu L, Liu S, Chen J, Tong S. Association between processed and unprocessed red meat consumption and risk of nonalcoholic fatty liver disease: A systematic review and dose-response meta-analysis. J Glob Health 2024; 14:04060. [PMID: 38665062 PMCID: PMC11046257 DOI: 10.7189/jogh.14.04060] [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: 04/28/2024] Open
Abstract
Background The nature of the relationship between red meat consumption and nonalcoholic fatty liver disease (NAFLD) remains unclear. Through this meta-analysis, we aimed to determine the association and dose-response relationship between red meat consumption (both processed and unprocessed) and the risk of NAFLD. Methods We systematically searched CENTRAL, PubMed, Embase, Web of Science and Scopus from inception to February 2022 for observational studies in which the exposure of interest was red meat consumption; the outcome of interest was the risk of NAFLD; and where odds ratios (ORs) or risk ratios were provided or could be calculated. We used random-effects meta-analyses to pool the effect sizes and performed analyses to estimate the linearity of the dose-response relationships between red meat intake and NAFLD risk. Results We included 10 studies in this review. The meta-analysis showed a significant association between the intake of red meat (OR = 1.27; 95% confidence interval (CI) = 1.07-1.50, P = 0.000, I2 = 81%), processed red meat (OR = 1.20; 95% CI = 1.04-1.3, P = 0.162, I2 = 34.9%) or unprocessed red meat (OR = 1.28; 95% CI = 1.05-1.55, P = 0.001, I2 = 76.2%) and the risk of NAFLD. We also found a significant linear dose-response association between processed red meat intake and NAFLD, with each 25-g increment of processed red meat intake per day was associated with an 11.1% higher risk of NAFLD (OR = 1.11; 95% CI = 1.01-1.22, P = 0.029), and a nonlinear association between unprocessed meat intake and NAFLD (P = 0.003 for nonlinearity). Conclusions Our findings indicate a potential positive association between red meat consumption (both processed and unprocessed) and NAFLD risk, especially in relation to increased intake of processed red meat compared to unprocessed red meat. However, caution is advised in interpreting these results; further research could establish a clearer understanding of the relationship between red meat consumption and NAFLD risk. Registration PROSPERO: CRD42022332839.
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Affiliation(s)
- Qin Zhou
- Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huaidong Hu
- Department of Endocrinology and Metabolism, Chongqing General Hospital, Chongqing, China
| | - Lina Hu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shuaibin Liu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jin Chen
- Department of Evidence-based Medicine and Clinical Epidemiology, West China Medical School of Medicine/West China Hospital, Sichuan University, Chengdu, China
| | - Shiwen Tong
- Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Zhang Z, Wang H, Chen M, Chen Y. L-shaped association between the GA/HbA1c ratio and all-cause mortality in U.S. adults with NAFLD: a cross-sectional study from the NHANES 1999-2004. BMC Endocr Disord 2024; 24:35. [PMID: 38468235 PMCID: PMC10926622 DOI: 10.1186/s12902-024-01568-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 03/05/2024] [Indexed: 03/13/2024] Open
Abstract
OBJECTIVE It is currently unclear whether there is a relationship between the ratio of glycated albumin to hemoglobin A1c (GA/HbA1c) and mortality in individuals diagnosed with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to investigate the relationship between the GA/HbA1c ratio and all-cause mortality in adults with NAFLD in the U.S. METHODS The investigation included a total of 5,295 individuals aged ≥ 18 years who were diagnosed with NAFLD, these individuals were selected from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. To evaluate the outcomes of death, the researchers relied on National Death Index (NDI) records up to December 31, 2019. To better understand the nonlinear relationship between the GA/HbA1c ratio and mortality among individuals with NAFLD, this study employed both subgroup and sensitivity analyses. Furthermore, Cox proportional hazards models and two-part Cox proportional hazards model were utilized. RESULTS The study included a total of 5,295 adult patients with NAFLD in the U.S. During a median follow-up period of 16.9 years, there were 1,471 recorded deaths, including 419 cardiovascular deaths. After accounting for various factors, a higher GA/HbA1c ratio exhibited a positive and nonlinear association with an increased risk of all-cause mortality in patients with NAFLD. Furthermore, the study revealed an L-shaped relationship between the GA/HbA1c ratio and all-cause mortality, with the inflection point occurring at a GA/HbA1c ratio of 2.21. When the GA/HbA1c ratio exceeded 2.21, each 1-unit increase in the ratio was associated with a 33% increase in the adjusted hazard ratio (HR 1.33; 95% CI 1.14, 1.60) for all-cause mortality. CONCLUSIONS A nonlinear correlation between the ratio of GA to HbA1c and all-cause mortality was observed in U.S. adults with NAFLD. In addition, an elevated GA/HbA1c ratio was linked to an increased risk of all-cause mortality in these patients.
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Affiliation(s)
- Zhaofu Zhang
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China
| | - Hao Wang
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China
| | - Mingyu Chen
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China
| | - Youpeng Chen
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
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Ayres ABS, Carneiro CRG, Gestic MA, Utrini MP, Chaim FDM, Callejas-Neto F, Chaim EA, Cazzo E. Identification of Predictors of Non-alcoholic Steatohepatitis and Its Severity in Individuals Undergoing Bariatric Surgery. Obes Surg 2024; 34:456-466. [PMID: 38097891 DOI: 10.1007/s11695-023-06986-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/28/2023] [Accepted: 12/06/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND As obesity reached epidemic proportions, non-alcoholic fatty liver disease (NAFLD) also had a worrisome parallel increase. The non-invasive differentiation of non-alcoholic steatohepatitis (NASH) from uncomplicated NAFLD remains an important challenge in current clinical practice. OBJECTIVE To identify predictors of the occurrence and severity of NAFLD and NASH. METHODS This is an analytical cross-sectional study which included individuals undergoing bariatric surgery. Participants were histologically classified according to the presence NASH and severity of NAFLD. Demographic, clinical, anthropometric, and biochemical aspects were analyzed and compared. RESULTS Out of 171 individuals, 87.7% were female and the mean age was 38.4±9.3 years. The average BMI was 38±3.0 kg/m2. NAFLD was histologically confirmed in 74.9%; the commonest histopathological abnormalities were macrovesicular steatosis (74.9%) and ballooning (40.4%). Simple steatosis occurred in 30.4%, 44.4% presented with NASH, and 31% had severe NAFLD. NASH associated with higher levels of ALT (0.03), ALP (0.02), and glucose (0.02). Cutoff values were, respectively, 23 U/L, 67 U/L, and 81 mg/dL. Their concomitant use provided an 83.1% specificity for NASH. Severe NAFLD associated with diabetes (p=0.02), higher BMI (p=0.01), AST (p=0.04), ALT (p<0.01), ALP (p=0.01), glucose (p=0.02), and ferritin (p<0.01). BMI over 39.3 kg/m2 and ferritin over 178 ng/mL concomitantly provided a 70.5% accuracy for severe NAFLD. CONCLUSIONS NASH and severe NAFLD associated with higher levels of ALT, ALP, and glucose. Severe NAFLD associated with higher BMI and higher ferritin levels in this group. The concomitant evaluation of these laboratory tests could help ruling out NASH and safely screening severe NAFLD.
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Affiliation(s)
- Arthur Balestra Silveira Ayres
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | | | - Martinho Antonio Gestic
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Murillo Pimentel Utrini
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Felipe David Mendonça Chaim
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Francisco Callejas-Neto
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Elinton Adami Chaim
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil
| | - Everton Cazzo
- Dept. of Surgery-School of Medical Sciences-State University of Campinas (UNICAMP), Rua Alexander Fleming, s/no, Campinas, (SP), Brazil.
- Cidade Universitária Zeferino Vaz, Campinas, (SP), CEP 13085-000, Brazil.
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Ho WL, Chen HH, Chen PK, Liao TL, Chang SH, Chen YM, Lin CH, Tang KT, Chen DY. Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study. BMJ Open 2024; 14:e079296. [PMID: 38272552 PMCID: PMC10824018 DOI: 10.1136/bmjopen-2023-079296] [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: 08/28/2023] [Accepted: 12/19/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors. DESIGN Retrospective study. SETTING Taiwan. PARTICIPANTS 2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence. OUTCOMES In this retrospective study using the 2000-2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs. RESULTS The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development. CONCLUSIONS We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.
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Affiliation(s)
- Wei-Li Ho
- Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Chiayi Branch, Chiayi, Taiwan
| | - Hsin-Hua Chen
- Division of General Medicine, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- PhD Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Big Data Center, National Chung Hsing University, Taichung, Taiwan
- Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Po-Ku Chen
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Tsai-Ling Liao
- PhD Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shih-Hsin Chang
- PhD Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Yi-Ming Chen
- PhD Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ching-Heng Lin
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kuo-Tung Tang
- PhD Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Der-Yuan Chen
- PhD Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
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Kannan S, Nelliyanil M, Mendagudli R, Rajeshwari S, Kona C, Kundapur R, Sathyanath S, Kulkarni V, Aggarwal S. Evaluation of risk factors for non-alcoholic fatty liver disease in India: A systematic review and meta-analysis. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2024; 12:435. [PMID: 38464628 PMCID: PMC10920698 DOI: 10.4103/jehp.jehp_208_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/23/2023] [Indexed: 03/12/2024]
Abstract
INTRODUCTION NAFLD is emerging as an important cause of liver disease in India. It is estimated that 16-32% of general population in India (nearly 120 million) has NAFLD. OBJECTIVE This study aimed to identify the risk factors of NAFLD and to identify the association of lifestyle (dietary and physical activity), genetic, and environmental factors with NAFLD in India. MATERIALS AND METHODS A systematic literature search was conducted using an international electronic database: PubMed (MEDLINE) and Google Scholar from the date of inception 31st March 2021 to 28th September 2021. We included studies examining patients with NAFLD: Adults above 18 years of age. Studies with or without a control population were both eligible. The studies with a diagnosis of NAFLD based solely on abnormal liver tests were excluded. We tried to get unpublished data but they were not of the quality of inclusion. Meta-analysis was performed using the software STATA 14.2 (StataCorp, College Station, TX, USA). For each of the studies, the standard error was calculated using the reported number of outcomes and the sample size. A forest plot was used to graphically represent the study-specific and pooled prevalence estimates for overall and subgroup analysis. RESULTS In a systematic review and meta-analysis of 8 studies including data from over 1800 individuals, we found that among components of lipid profile, LDL and HDL had a negative effects on NAFLD while triglycerides had a positive effect on NAFLD. CONCLUSION Type 2 Diabetes Mellitus, Hypertension, and Obesity were the potential risk factors for NAFLD but the evidence generated was only from single studies.
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Affiliation(s)
- Suthanthira Kannan
- Department of Community Medicine, ESIC Medical College, Chennai, Tamil Nadu, India
| | - Maria Nelliyanil
- Department of Community Medicine, AJ Institute of Medical Sciences and Research Center, Mangalore, Karnataka, India
| | - Roopa Mendagudli
- Department of Community Medicine, MR Medical College, Kalaburgai, Karnataka, India
| | - Swetha Rajeshwari
- Department of Community Medicine, ESIC Medical College, Sanathnagar, Hyderabad, Telangana, India
| | - Chandralekha Kona
- Department of Community Medicine and Family Medicine, AIIMS Bibinagar, Hyderabad, Telangana, India
| | - Rashmi Kundapur
- Department of Community Medicine and Family Medicine, AIIMS Bibinagar, Hyderabad, Telangana, India
| | - Shreyaswi Sathyanath
- Department of Community Medicine, AJ Institute of Medical Sciences and Research Center, Mangalore, Karnataka, India
| | - Vaman Kulkarni
- Department of Community Medicine and Family Medicine, AIIMS Bibinagar, Hyderabad, Telangana, India
| | - Sumit Aggarwal
- Scientist and Program Officer, ICMR, Headquarters, New Delhi, India
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Harden JE, Tabacu L, Reynolds LJ. Physical activity intensity and markers of inflammation in those with non-alcoholic fatty liver disease. Diabetes Res Clin Pract 2024; 207:111047. [PMID: 38070545 DOI: 10.1016/j.diabres.2023.111047] [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: 09/01/2023] [Revised: 11/14/2023] [Accepted: 12/05/2023] [Indexed: 02/10/2024]
Abstract
AIMS To investigate associations between objectively measured light (LPA) and moderate-to-vigorous (MVPA) physical activity on plasma homocysteine and serum C-reactive protein (CRP) in individuals with Non-Alcoholic Fatty Liver Disease (NAFLD). METHODS This study was a secondary analysis using data from 2003 to 2006 National Health and Nutrition Examination Survey including a total of 983 individuals with NAFLD. Physical activity was assessed over 7 days with accelerometers. Participants were split into tertiles based on average daily minutes of LPA or MVPA and CRP and homocysteine were assessed across tertiles. RESULTS Adjusted plasma homocysteine and CRP were not different between groups regarding levels of LPA (Homocysteine: 1st tertile - 10.4 ± 0.7 µmol/L; 2nd tertile - 9.6 ± 0.4 µmol/L; 3rd tertile - 9.6 ± 0.4 µmol/L; p = 0.28; CRP: 1st tertile - 0.79 ± 0.12 mg/dL; 2nd tertile - 0.73 ± 0.09 mg/dL; 3rd tertile - 0.73 ± 0.09 mg/dL; p = 0.72). Adjusted CRP was significantly (p = 0.02) different across MVPA tertiles (1st: 0.87 ± 0.13 mg/dL; 2nd: 0.75 ± 0.10 mg/dL; 3rd:0.65 ± 0.09). CONCLUSIONS LPA does not appear to be effective at improving homocysteine or CRP levels in individuals with NAFLD. However, MVPA may be an effective therapy for decreasing CRP in NAFLD patients.
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Affiliation(s)
- Joel E Harden
- School of Exercise Science, Old Dominion University, Norfolk, VA, USA
| | - Lucia Tabacu
- Department of Mathematics and Statistics, Old Dominion University, Norfolk, VA, USA
| | - Leryn J Reynolds
- School of Exercise Science, Old Dominion University, Norfolk, VA, USA.
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Zhao E, Cheng Y, Yu C, Li H, Fan X. The systemic immune-inflammation index was non-linear associated with all-cause mortality in individuals with nonalcoholic fatty liver disease. Ann Med 2023; 55:2197652. [PMID: 37052341 PMCID: PMC10115001 DOI: 10.1080/07853890.2023.2197652] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/14/2023] Open
Abstract
OBJECTIVE Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD. METHODS Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan-Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines. RESULTS A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47-2.37; p < 0.0001). After controlling for confounders, an increase in log2-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26-1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log2-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log2-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71-1.15, p = 0.419). However, a higher log2-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49-2.02, p < 0.001). Based on a study of US NAFLD patients, it was found that the baseline log2-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients.KEY MESSAGESUsing a large nationally representative survey of individuals among US adults, the study demonstrated that log2-SII was J-shaped and associated with all-cause death among individuals with NAFLD.Spline analyses demonstrated that the association between log2-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8.Higher log2-SII associated with poor survival in NAFLD.
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Affiliation(s)
- Enfa Zhao
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
| | - Chunxiao Yu
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
| | - Huijie Li
- Department of Statistics and Medical Records Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiude Fan
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
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14
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Younossi ZM, Zelber-Sagi S, Henry L, Gerber LH. Lifestyle interventions in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2023; 20:708-722. [PMID: 37402873 DOI: 10.1038/s41575-023-00800-4] [Citation(s) in RCA: 117] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/26/2023] [Indexed: 07/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a dynamic chronic liver disease that develops in close association with metabolic irregularities. Between 2016 and 2019, the global prevalence among adults was reported as 38% and among children and adolescents it was about 10%. NAFLD can be progressive and is associated with increased mortality from cardiovascular disease, extrahepatic cancers and liver complications. Despite these numerous adverse outcomes, no pharmacological treatments currently exist to treat nonalcoholic steatohepatitis, the progressive form of NAFLD. Therefore, the main treatment is the pursuit of a healthy lifestyle for both children and adults, which includes a diet rich in fruits, nuts, seeds, whole grains, fish and chicken and avoiding overconsumption of ultra-processed food, red meat, sugar-sweetened beverages and foods cooked at high heat. Physical activity at a level where one can talk but not sing is also recommended, including leisure-time activities and structured exercise. Avoidance of smoking and alcohol is also recommended. Policy-makers, community and school leaders need to work together to make their environments healthy by developing walkable and safe spaces with food stores stocked with culturally appropriate and healthy food items at affordable prices as well as providing age-appropriate and safe play areas in both schools and neighbourhoods.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA.
- Inova Medicine, Inova Health System, Falls Church, VA, USA.
| | | | - Linda Henry
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
- Inova Medicine, Inova Health System, Falls Church, VA, USA
| | - Lynn H Gerber
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
- Inova Medicine, Inova Health System, Falls Church, VA, USA
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15
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Avelar-Rodríguez D, Peña-Vélez R, Popov J, Hill L, Ryan PM. Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:418-427. [PMID: 36412490 DOI: 10.17235/reed.2022.8796/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
BACKGROUND non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. METHODS PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. RESULTS five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). CONCLUSIONS there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.
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Affiliation(s)
| | - Rubén Peña-Vélez
- Gastroenterología y Nutrición, Hospital General de Puebla "Dr. Eduardo Vázquez N", México
| | - Jelena Popov
- College of Medicine and Health. University College Cork
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Schreiner AD, Sattar N. Identifying Patients with Nonalcoholic Fatty Liver Disease in Primary Care: How and for What Benefit? J Clin Med 2023; 12:4001. [PMID: 37373694 DOI: 10.3390/jcm12124001] [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: 02/28/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023] Open
Abstract
Despite its increasing prevalence, nonalcoholic fatty liver disease (NAFLD) remains under-diagnosed in primary care. Timely diagnosis is critical, as NAFLD can progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and death; furthermore, NAFLD is also a risk factor linked to cardiometabolic outcomes. Identifying patients with NAFLD, and particularly those at risk of advanced fibrosis, is important so that healthcare practitioners can optimize care delivery in an effort to prevent disease progression. This review debates the practical issues that primary care physicians encounter when managing NAFLD, using a patient case study to illustrate the challenges and decisions that physicians face. It explores the pros and cons of different diagnostic strategies and tools that physicians can adopt in primary care settings, depending on how NAFLD presents and progresses. We discuss the importance of prescribing lifestyle changes to achieve weight loss and mitigate disease progression. A diagnostic and management flow chart is provided, showing the key points of assessment for primary care physicians. The advantages and disadvantages of advanced fibrosis risk assessments in primary care settings and the factors that influence patient referral to a hepatologist are also reviewed.
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Affiliation(s)
- Andrew D Schreiner
- Department of Medicine, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USA
| | - Naveed Sattar
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
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Chen K, Pan Y, Xiang X, Meng X, Yao D, Lin L, Li X, Wang Y. The nonalcoholic fatty liver risk in prediction of unfavorable outcome after stroke: A nationwide registry analysis. Comput Biol Med 2023; 157:106692. [PMID: 36924734 DOI: 10.1016/j.compbiomed.2023.106692] [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: 12/25/2022] [Revised: 01/31/2023] [Accepted: 02/14/2023] [Indexed: 03/05/2023]
Abstract
Few researches have looked at the relationship between nonalcoholic fatty liver disease (NAFLD) at the time of admission and the long-term outcomes of patients suffering from acute ischemic stroke (AIS). We aimed to probe the relationship between NAFLD risk evaluated by NAFLD indices and long-term endpoints, along with the prognostic value of merging NAFLD indices with established risk markers for the prognosis of AIS patients. The fatty liver index (FLI) and the Hepatic steatosis index (HSI) were used to evaluate NAFLD risk in the Third China National Stroke Registry (CNSR-III), a large, prospective, national, multicenter cohort registry study. NAFLD was defined as FLI ≥35 for males and FLI ≥ 20 for females, as well as HSI>36. Death or major disability (modified Rankin Scale score ≥3) were the primary outcomes following the beginning of a stroke. On patient outcomes, the prognostic performance of two objective NAFLD parameters was evaluated. NAFLD was detected in 32.10-51.90% of AIS patients. After 1-year, 14.5% of the participants had died or suffered a severe outcome. After controlling for known risk factors, NAFLD was associated with a modest probability of adverse outcome (odds ratio,0.72[95% CI, 0.61-0.86] for FLI; odds ratio,0.68[95% CI, 0.55-0.85] for HSI). The inclusion of the two NAFLD indicators in the conventional prediction model was justified by the integrated discrimination index, continuing to increase the model's overall predictive value for long-term adverse outcomes. NAFLD risk was linked to a lower risk of long-term death or major disability in people with AIS. The predictive value of objective NAFLD after AIS was demonstrated in our study.
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Affiliation(s)
- Keyang Chen
- Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Research Units of Clinical Translation of Cell Growth Factors and Diseases Research, Chinese Academy of Medical Science, Wenzhou Medical University, Wenzhou, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xianglong Xiang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xia Meng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Dongxiao Yao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Li Lin
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China; Research Units of Clinical Translation of Cell Growth Factors and Diseases Research, Chinese Academy of Medical Science, Wenzhou Medical University, Wenzhou, China
| | - Xiaokun Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China; Research Units of Clinical Translation of Cell Growth Factors and Diseases Research, Chinese Academy of Medical Science, Wenzhou Medical University, Wenzhou, China.
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, China; Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, 2019RU018, China.
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Sempokuya T, Warner J, Azawi M, Nogimura A, Wong LL. Current status of disparity in liver disease. World J Hepatol 2022; 14:1940-1952. [PMID: 36483604 PMCID: PMC9724102 DOI: 10.4254/wjh.v14.i11.1940] [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: 09/18/2022] [Revised: 11/09/2022] [Accepted: 11/16/2022] [Indexed: 11/24/2022] Open
Abstract
Disparities have emerged as an important issue in many aspects of healthcare in developed countries and may be based on race, ethnicity, sex, geographical location, and socioeconomic status. For liver disease specifically, these potential disparities can affect access to care and outcome in viral hepatitis, chronic liver disease, and hepatocellular carcinoma. Shortages in hepatologists and medical providers versed in liver disease may amplify these disparities by compromising early detection of liver disease, surveillance for hepatocellular carcinoma, and prompt referral to subspecialists and transplant centers. In the United States, continued efforts have been made to address some of these disparities with better education of healthcare providers, use of telehealth to enhance access to specialists, reminders in electronic medical records, and modifying organ allocation systems for liver transplantation. This review will detail the current status of disparities in liver disease and describe current efforts to minimize these disparities.
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Affiliation(s)
- Tomoki Sempokuya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Josh Warner
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Muaataz Azawi
- Division of Gastroenterology and Hepatology, Sanford Center for Digestive Health, Sioux Falls 57105, SD, Uruguay
| | - Akane Nogimura
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Aichi, Japan
- Division of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Aichi, Japan
| | - Linda L Wong
- Department of Surgery, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, United States
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Bjørnå ER, Engelsen MT, El-Serag HB, Ness-Jensen E. Prevalence and risk factors of nonalcoholic fatty liver disease in a general population, the HUNT study. Scand J Gastroenterol 2022; 58:505-511. [PMID: 36314512 DOI: 10.1080/00365521.2022.2139633] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the metabolic syndrome is the main risk factor. Alanine aminotransferase (ALT) is widely used to screen for NAFLD, and the aims of this study were to assess the prevalence and risk factors of NAFLD in a general population. METHODS The study was based on the third population-based Trøndelag Health Study (HUNT3), Norway, performed 2006-2008. In HUNT3, ALT and lipids were analyzed, anthropometric measures done, and comorbidity and risk factors reported. Elevated ALT was used to define NAFLD and participants with other diagnosed liver diseases and excessive alcohol consumption were excluded. Multivariable logistic regression reporting odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors. RESULTS In HUNT3, 2373 (4.7%) of 50,006 participants were diagnosed with NAFLD. The risk increased with obesity (OR 1.73, 95% CI 1.46-2.05) and very increased waist circumference (OR 1.97, 95% CI 1.65-2.35), and the risk increased dose-dependently (p for trend <0.001). Hypertension (OR 1.58, 95% CI 1.42-1.76), diabetes mellitus (OR 1.48, 95% CI 1.30-1.68), high triglycerides (OR 1.55, 95% CI 1.41-1.71), high total cholesterol (OR 1.52, 95% CI 1.29-1.81) and low high-density lipoproteins (OR 1.33, 95% CI 1.21-1.47) also increased the risk of NAFLD. The risk was lower in men (OR 0.71, 95% CI 0.64-0.79) and among current smokers (OR 0.79, 95% CI 0.70-0.89). CONCLUSION NAFLD is a common condition in the general population. NAFLD should be suspected in individuals with abdominal obesity, hypertension, diabetes mellitus and dyslipidemias.
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Affiliation(s)
- Erika R Bjørnå
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
| | - Martine T Engelsen
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
| | - Hashem B El-Serag
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Eivind Ness-Jensen
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.,Medical Department, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.,Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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20
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Evstifeeva SE, Shalnova SA, Kutsenko VA, Yarovaya EV, Balanova YA, Imaeva AE, Kapustina AV, Muromtseva GA, Maksimov SA, Karamnova NS, Soplenkova AG, Filichkina EM, Viktorova IA, Prishchepa NN, Redko AN, Yakushin SS, Drapkina OM. Prevalence of non-alcoholic fatty liver disease among the working-age population: associations with socio-demographic indicators and behavioral risk factors (ESSE RF-2 data). КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2022. [DOI: 10.15829/1728-8800-2022-3356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Aim. To assess the prevalence of non-alcoholic fatty liver disease (NAFLD) using the liver obesity index — FLI (Fatty Liver Index), and to study its associations with socio-demographic indicators and behavioral risk factors for NAFLD.Material and methods. The data from the multicenter ESSE-RF study (Epidemiology of cardiovascular diseases in the regions of the Russian Federation) — samples from the unorganized male and female population aged 25-64 years were used. 5,161 respondents were included, of which 2,275 (44,1%) were men. To assess the prevalence of NAFLD, the liver obesity index FLI was used, calculated according to the formula by Bedogni G, et al. (2006). A high FLI index ≥60 was considered a predictor of liver steatosis.Results. High FLI ≥60 was detected in 38,5% of men and 26,6% of women. Multivariate analysis of associations of high FLI index in men and women showed a strong relationship with age: men — odds ratio (OR) 5,01, 95% confidence interval (CI): 3,82-6,59 (p<0,0001) and women — OR 8,58, 95% CI: 6,39-11,64 (p<0,0001), living in rural areas: men — OR 1,32, 95% CI: 1,06-1,63 (p=0,011) and women — OR 1,4, 95% CI: 1,15-1,71 (p=0,001). The FLI index ≥60 was significantly associated with low physical activity (p=0,001) in men and current smoking in women (p=0,013).Conclusion. A high FLI index ≥60 is most common among men, significantly associated with age, living in rural areas, currently smoking women, and low physical activity men. Higher education, in relation to FLI ≥60, had a protective effect on women.
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Affiliation(s)
- S. E. Evstifeeva
- National Medical Research Center for Therapy and Preventive Medicine
| | - S. A. Shalnova
- National Medical Research Center for Therapy and Preventive Medicine
| | - V. A. Kutsenko
- National Medical Research Center for Therapy and Preventive Medicine;
Lomonosov Moscow State University
| | - E. V. Yarovaya
- National Medical Research Center for Therapy and Preventive Medicine;
Lomonosov Moscow State University
| | - Yu. A. Balanova
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. E. Imaeva
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. V. Kapustina
- National Medical Research Center for Therapy and Preventive Medicine
| | - G. A. Muromtseva
- National Medical Research Center for Therapy and Preventive Medicine
| | - S. A. Maksimov
- National Medical Research Center for Therapy and Preventive Medicine
| | - N. S. Karamnova
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. G. Soplenkova
- National Medical Research Center for Therapy and Preventive Medicine
| | - E. M. Filichkina
- National Medical Research Center for Therapy and Preventive Medicine
| | | | | | | | | | - O. M Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
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21
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Wang H, Sun R, Yang S, Ma X, Yu C. Association between serum ferritin level and the various stages of non-alcoholic fatty liver disease: A systematic review. Front Med (Lausanne) 2022; 9:934989. [PMID: 35991666 PMCID: PMC9381877 DOI: 10.3389/fmed.2022.934989] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 07/18/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder across the world, and non-invasive evaluation approaches are in need to assess NAFLD disease progression. Serum ferritin has been proposed as one of the biomarkers for NAFLD diagnosis in previous studies. This systematic review aims to identify, report, and synthesize studies that investigated the association of serum ferritin level with the various stages of NAFLD among the adult population. Methods Three databases - MEDLINE, EMBASE, and Scopus - were systematically searched to obtain potentially relevant publications before July 2022. No restrictions were applied to geographical region, study design, publication type and language. The association between serum ferritin level or different ferritin categories and the various stages of NAFLD was the primary outcome of interest. Title and abstract screenings, data extraction and coding, and quality assessment were independently completed by two authors with discrepancies resolved through discussion with a third author. Results Thirty-two studies were included and heterogeneity was considerable. The associations between serum ferritin level and the stages of hepatic steatosis, fibrosis, inflammation and ballooning and the occurrence of non-alcoholic steatohepatitis (NASH) were investigated but inconsistent associations were reported. Most studies identified serum ferritin to be a predictor of advanced NAFLD, while several revealed the opposite end. Conclusions Serum ferritin could be considered to act as a non-invasive biomarker for assessing various stages of NAFLD. Nevertheless, further studies are still in need to confirm its predictive value since this study reported inconsistent associations based on the qualitative synthesis. Systematic Review Registration http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021275630.
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Affiliation(s)
- Huanqiu Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ruyu Sun
- Institute of Social Medicine, School of Medicine, Zhejiang University, Hangzhou, China
| | - Sisi Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xueqing Ma
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chengbo Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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22
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Chen X, Zhang L, Zheng L, Tuo B. Role of Ca 2+ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review). Int J Mol Med 2022; 50:113. [PMID: 35796003 PMCID: PMC9282635 DOI: 10.3892/ijmm.2022.5169] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 06/07/2022] [Indexed: 01/10/2023] Open
Affiliation(s)
- Xingyue Chen
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Li Zhang
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Liming Zheng
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
| | - Biguang Tuo
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
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23
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Rostamizadeh P, Asl SMKH, Far ZG, Ahmadijoo P, Mahmudiono T, Bokov DO, Alsaikhan F, Jannat B, Mazloom Z. Effects of licorice root supplementation on liver enzymes, hepatic steatosis, metabolic and oxidative stress parameters in women with nonalcoholic fatty liver disease: A randomized double-blind clinical trial. Phytother Res 2022; 36:3949-3956. [PMID: 35785498 DOI: 10.1002/ptr.7543] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 05/09/2022] [Accepted: 06/14/2022] [Indexed: 12/14/2022]
Abstract
This study aimed to evaluate the effects of licorice root supplementation on liver enzymes, hepatic steatosis, metabolic and oxidative stress parameters in women with nonalcoholic fatty liver disease (NAFLD). In this randomized double-blind, placebo-controlled trial, 60 women with NAFLD were selected and randomly assigned into 2 groups to take 1,000 mg/day powder of licorice root extract or placebo for 12 weeks. In addition, all the patients were advised to follow a weight loss diet and healthy lifestyle. The plasma levels of liver enzymes, glycemic indices, lipid profile, oxidative stress parameters, as well as hepatic steatosis were measured at the beginning and end of the study. Through the 12-weeks period of supplementation, women who received powder of licorice root experienced a statistically significant improvement in alanine aminotransferase (p < .001), insulin (p = .002), insulin resistance (p = .003), malondialdehyde (p < .001) serum levels, and ultrasonographic findings of liver steatosis (p < .001), compared to the placebo group. In conclusion, licorice root supplementation in addition to gradual weight loss and lifestyle modification is superior to lifestyle modification alone for the treatment of NAFLD.
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Affiliation(s)
- Pouya Rostamizadeh
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Zohreh Ghaem Far
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Pegah Ahmadijoo
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Trias Mahmudiono
- Department of Nutrition, Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia
| | - Dmitry Olegovich Bokov
- Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russia.,Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow, Russia
| | - Fahad Alsaikhan
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-kharj, Saudi Arabia
| | - Behrooz Jannat
- Halal Research Center of IRI, Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran
| | - Zohreh Mazloom
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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24
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Zhao CZ, Jiang W, Zhu YY, Wang CZ, Zhong WH, Wu G, Chen J, Zhu MN, Wu QL, Du XL, Luo YY, Li M, Wang HL, Zhao H, Ma QG, Zhong GY, Wei RR. Highland barley Monascus purpureus Went extract ameliorates high-fat, high-fructose, high-cholesterol diet induced nonalcoholic fatty liver disease by regulating lipid metabolism in golden hamsters. JOURNAL OF ETHNOPHARMACOLOGY 2022; 286:114922. [PMID: 34923087 DOI: 10.1016/j.jep.2021.114922] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/09/2021] [Accepted: 12/14/2021] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine. AIM OF THE STUDY This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD). MATERIALS AND METHODS HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed. RESULTS Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1). CONCLUSIONS HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.
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Affiliation(s)
- Cui-Zhu Zhao
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Wei Jiang
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Yu-Ye Zhu
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Chong-Zhi Wang
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, 60637, United States; Department of Anesthesia & Critical Care, The University of Chicago, Chicago, 60637, United States
| | - Wei-Hong Zhong
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Guang Wu
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Jie Chen
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Mei-Ning Zhu
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Qi-Lin Wu
- Tibet Yuewang Medicine Diagnosis Ecological Tibetan Medicine Technology Co., Ltd., Lhasa, 850000, PR China
| | - Xiao-Lang Du
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Ying-Ying Luo
- State Key Laboratory of Innovative Drugs and High Efficiency Energy Saving and Consumption Reduction Pharmaceutical Equipment & National Engineering Center for Manufacturing Technology of Solid Preparation of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Min Li
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Hong-Ling Wang
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China
| | - Hui Zhao
- Tibet Yuewang Medicine Diagnosis Ecological Tibetan Medicine Technology Co., Ltd., Lhasa, 850000, PR China; National United Engineering Research Center for Tibetan Plateau Microbiology, Lhasa, 850000, PR China
| | - Qin-Ge Ma
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China; Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, 60637, United States; Department of Anesthesia & Critical Care, The University of Chicago, Chicago, 60637, United States.
| | - Guo-Yue Zhong
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China.
| | - Rong-Rui Wei
- Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine & Key Laboratory of Modern Preparation of Chinese Medicine of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, PR China.
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Chen HX, Yang F, He XQ, Li T, Sun YZ, Song JP, Huang XA, Guo WF. Garcinia Biflavonoid 1 Improves Lipid Metabolism in HepG2 Cells via Regulating PPARα. Molecules 2022; 27:molecules27061978. [PMID: 35335339 PMCID: PMC8950208 DOI: 10.3390/molecules27061978] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/15/2022] [Accepted: 03/15/2022] [Indexed: 02/04/2023] Open
Abstract
Garcinia biflavonoid 1 (GB1) is one of the active chemical components of Garcinia kola and is reported to be capable of reducing the intracellular lipid deposition, which is the most significant characteristic of non-alcoholic fatty liver disease. However, its bioactive mechanism remains elusive. In the current study, the lipid deposition was induced in HepG2 cells by exposure to oleic acid and palmitic acid (OA&PA), then the effect of GB1 on lipid metabolism and oxidative stress and the role of regulating PPARα in these cells was investigated. We found that GB1 could ameliorate the lipid deposition by reducing triglycerides (TGs) and upregulate the expression of PPARα and SIRT6, suppressing the cell apoptosis by reducing the oxidative stress and the inflammatory factors of ROS, IL10, and TNFα. The mechanism study showed that GB1 had bioactivity in a PPARα-dependent manner based on its failing to improve the lipid deposition and oxidative stress in PPARα-deficient cells. The result revealed that GB1 had significant bioactivity on improving the lipid metabolism, and its potential primary action mechanism suggested that GB1 could be a potential candidate for management of non-alcoholic fatty liver disease.
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Affiliation(s)
- Hai-Xin Chen
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
| | - Fan Yang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
| | - Xin-Qian He
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
| | - Ting Li
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
| | - Yong-Zhi Sun
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
| | - Jian-Ping Song
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Xin-An Huang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Correspondence: (X.-A.H.); (W.-F.G.)
| | - Wen-Feng Guo
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; (H.-X.C.); (F.Y.); (X.-Q.H.); (T.L.); (Y.-Z.S.); (J.-P.S.)
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Correspondence: (X.-A.H.); (W.-F.G.)
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Farnesoid X Receptor Deficiency Induces Hepatic Lipid and Glucose Metabolism Disorder via Regulation of Pyruvate Dehydrogenase Kinase 4. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3589525. [PMID: 35251469 PMCID: PMC8896157 DOI: 10.1155/2022/3589525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/18/2022] [Accepted: 02/01/2022] [Indexed: 12/19/2022]
Abstract
Farnesoid X receptors (FXR) are bile acid receptors that play roles in lipid, glucose, and energy homeostasis. Synthetic FXR-specific agonists have been developed for treating nonalcoholic fatty liver disease (NAFLD) patients. However, the detailed mechanism remains unclear. To investigate the effects of FXR on NAFLD and the possible mechanism, FXR-null mice were fed either a normal or a high-fat diet. The FXR-null mice developed hepatomegaly, steatosis, accumulation of lipid droplets in liver cells, glucose metabolism disorder, and elevated serum lipid levels. Transcriptomic results showed increased expression of key lipid synthesis and glucose metabolism-related proteins. We focused on pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme involved in the regulation of glucose and fatty acid (FA) metabolism and homeostasis. Subsequently, we confirmed an increase in PDK4 expression in FXR knockout cells. Moreover, inhibition of PDK4 expression alleviated lipid accumulation in hepatocytes caused by FXR deficiency in vivo and in vitro. Our results identify FXR as a nuclear transcription factor that regulates glucose and lipid metabolism balance through PDK4, providing further insights into the mechanism of FXR agonists in the treatment of metabolic diseases.
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Han L, Zhang Y, Yue C, Huang Y, Wu Y, Chen J. Preliminary Study on Risk Factors for Morbidity of Nonalcoholic Fatty Liver Disease in High-Income Male Population. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:9331284. [PMID: 35251583 PMCID: PMC8890829 DOI: 10.1155/2022/9331284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 11/29/2021] [Accepted: 12/14/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Believed to be a result of metabolic syndrome and unhealthy lifestyle, the incidence of nonalcoholic fatty liver disease (NAFLD) has become a serious public health problem. Among the high-income male population, metabolic syndrome and unhealthy lifestyle are particularly prominent. Therefore, we conducted a survey on 375 high-income male subjects, expecting to understand the risk factors and related factors for morbidity of NAFLD among the high-income male population being physically examined in Shanghai. METHODS A cross-sectional study was applied to 375 high-income male subjects (including 190 patients with NAFLD and 185 non-NAFLD subjects) who were examined in the special needs clinic at Huadong Hospital affiliated to Fudan University. In combination with medical history, physical examination, and laboratory test results and by use of a self-made NAFLD health questionnaire, the basic data of the research objects were collected and the obtained data were subject to a correlation analysis. RESULTS This study investigated 375 high-income males, and the morbidity rate of NAFLD was 50.67%. The NAFLD group was higher than the non-NAFLD group in terms of body weight, BMI, systolic blood pressure, and diastolic blood pressure (P < 0.05). Hypertension (OR = 2.944), diabetes (OR = 7.278), and hyperuricemia (OR = 1.922) are the risk factors for NAFLD; compared with no metabolic diseases, one (OR = 1.848), two (OR = 2.417), and three metabolic diseases (OR = 14.788) are risk factors for the development of NAFLD. Compared with the non-NAFLD group, the NAFLD group had a higher level of WBC, RBC, Hb, PLT, FPG, HbA1c, ALT, AST, GGT, ALP, TP, and UA (P < 0.05). There was a statistically significant difference in the intake of supper and staple foods between the NAFLD group and the non-NAFLD group, and the highly greasy diet was a risk factor for NAFLD (OR = 2.173) as opposed to the nongreasy diet. CONCLUSION High-income male population is a high-risk group of NAFLD. Most of the patients with NAFLD have abnormal biochemical indicators as opposed to the healthy population and are more likely to be complicated with other chronic diseases or abnormal health status. And the occurrence of hypertension, diabetes, and hyperuricemia is the risk factor for the development of NAFLD. At the same time, the number of metabolic diseases complicated is also a risk factor for NAFLD as compared with the absence of complications with such metabolic diseases. Compared with a diet that is not greasy, the fact that high-income male NAFLD patients have a very greasy diet increases the risk of NAFLD.
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Affiliation(s)
- Li Han
- Huadong Hospital Affiliated to Fudan University, Department of Traditional Chinese Medicine, 221 Yan'an West Road,Jing'an District, Shanghai 200040, China
| | - Yuting Zhang
- Huadong Hospital Affiliated to Fudan University, Department of Digestion, 221 Yan'an West Road,Jing'an District, Shanghai 200040, China
| | - Cui Yue
- The Office of Good Clinical Practice, 221 West Yan'an Road, Huadong Hospital, Shanghai 200040, China
| | - Yiqin Huang
- Huadong Hospital Affiliated to Fudan University, Department of Digestion, 221 Yan'an West Road,Jing'an District, Shanghai 200040, China
| | - Yumin Wu
- Huadong Hospital Affiliated to Fudan University, Department of Nephrology, 221 Yan'an West Road,Jing'an District, Shanghai 200040, China
| | - Jie Chen
- Huadong Hospital Affiliated to Fudan University, Department of Geriatrics, 317 Room,168 Yan'an West Road,Jing'an District, Shanghai 200040, China
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Catanzaro R, Sciuto M, He F, Singh B, Marotta F. Non-alcoholic fatty liver disease: correlation with hyperuricemia in a European Mediterranean population. Acta Clin Belg 2022; 77:45-50. [PMID: 32559142 DOI: 10.1080/17843286.2020.1783907] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are two pathologies that intersect each other. It was found that there is an association between MetS/NAFLD and hyperuricemia. The aim of our study was to demonstrate this association in a European Mediterranean population. METHODS We compared 236 patients with NAFLD to 218 patients without NAFLD. We assessed laboratory metabolic parameters (serum uric acid - SUA, fasting glucose, triglycerides, total cholesterol, etc.) and the presence or absence of MetS in a retrospective, cross-sectional, case-control manner. RESULTS Analysis of the two main variables in study showed a moderate direct correlation (p< 0.01; Pearson coefficient 0.443) between SUA and NAFLD. Evaluation for SUA quartiles showed a decreased risk of NAFLD for the first and second quartiles (OR Q1 = 0.20; OR Q2 = 0.59), but increased for the third and fourth quartiles (OR Q3 = 2.22; OR Q4 = 6.97). In females, the risk of NAFLD was less compared to males for the first three quartiles of SUA, but it was more than double for the fourth quartile (OR Q1 0.21 vs 0.16; OR Q2 0.82 vs 0.45; OR Q3 2.50 vs 2.26; OR Q4 4.50 vs 9.83). In the NAFLD group, hyperuricemia was significantly correlated with sex, obesity, hypertension, and with the number of components of the MetS. In the Control group, SUA directly correlated with age, diabetes, and ALT, but not with obesity. CONCLUSION We have found a significant correlation between NAFLD and hyperuricemia. The higher SUA levels accompanied the risk of NAFLD.
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Affiliation(s)
- Roberto Catanzaro
- Department of Clinical and Experimental Medicine - Gastroenterology Section "Gaspare Rodolico" Policlinico Hospital, University of Catania, Catania, Italy
| | - Morena Sciuto
- Department of Clinical and Experimental Medicine - Gastroenterology Section "Gaspare Rodolico" Policlinico Hospital, University of Catania, Catania, Italy
| | - Fang He
- Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, China
| | - Birbal Singh
- ICAR-Indian Veterinary Research Institute, Regional Station Palampur, Karnal, India
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Huang YP, Zhang S, Zhang M, Wang Y, Wang WH, Li J, Li C, Lin JN. Gender-specific prevalence of metabolic-associated fatty liver disease among government employees in Tianjin, China: a cross-sectional study. BMJ Open 2021; 11:e056260. [PMID: 34911725 PMCID: PMC8679074 DOI: 10.1136/bmjopen-2021-056260] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES To explore the prevalence and risk factors of metabolic-associated fatty liver disease (MAFLD) in Tianjin government employees of different genders. DESIGN Cross-sectional study. SETTING Health Management Center of Tianjin Union Medical Center. PARTICIPANTS 16 924 government employees (59.6% male). MEASURES Ultrasound liver examination was performed to determine whether there is fat accumulation in the organ. Participants' weight and height were measured, and body mass index (BMI) was calculated. RESULTS The overall prevalence of MAFLD in this population was 40.76%. The rates were significantly higher in men (49.42%) than in women (27.97%). The prevalence of MAFLD was highest in men aged 40-49 years (54.04%) and women aged 60-69 years (43.44%). In all BMI groups, the prevalence was higher in men than that in women. In both genders, higher BMI was associated with the risk of MAFLD, especially for BMI ≥31.9 kg/m2. CONCLUSIONS The prevalence of MAFLD in government employees in Tianjin was significantly higher than the average level in China. The prevalence varied by sex and age group, and those with high BMI were at the highest risk of developing MAFLD.
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Affiliation(s)
- Ya-Ping Huang
- Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
| | - Shi Zhang
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
| | - Minying Zhang
- School of Medicine, Nankai University, Tianjin, China
| | - Yi Wang
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
| | - Wen-Hong Wang
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
| | - Jing Li
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
| | - Chunjun Li
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
| | - Jing-Na Lin
- Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University-Affiliated Hospital, Tianjin, China
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Zhang H, Zhang E, Hu H. Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies. Biomedicines 2021; 9:biomedicines9111660. [PMID: 34829889 PMCID: PMC8615581 DOI: 10.3390/biomedicines9111660] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 11/05/2021] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the chronic liver disease with the highest incidence throughout the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Abnormal iron metabolism, lipid peroxidation, and accumulation of polyunsaturated fatty acid phospholipids (PUFA-PLs) can all trigger ferroptosis. Emerging evidence indicates that ferroptosis plays a critical role in the pathological progression of NAFLD. Because the liver is the main organ for iron storage and lipid metabolism, ferroptosis is an ideal target for liver diseases. Inhibiting ferroptosis may become a new therapeutic strategy for the treatment of NAFLD. In this article, we describe the role of ferroptosis in the progression of NAFLD and its related mechanisms. This review will highlight further directions for the treatment of NAFLD and the selection of corresponding drugs that target ferroptosis.
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Affiliation(s)
- Han Zhang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100080, China;
| | - Enxiang Zhang
- Key Laboratory of Growth Regulation and Transformation Research of Zhejiang Province, School of Life Sciences, Westlake Institute for Advanced Study, Westlake University, Hangzhou 310024, China
- Correspondence: (E.Z.); (H.H.)
| | - Hongbo Hu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100080, China;
- Correspondence: (E.Z.); (H.H.)
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Hayat U, Siddiqui AA, Okut H, Afroz S, Tasleem S, Haris A. The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: A meta-analysis of 11 epidemiological studies. Ann Hepatol 2021; 20:100254. [PMID: 32920163 DOI: 10.1016/j.aohep.2020.08.071] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/24/2020] [Accepted: 08/24/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic liver disease. It is considered a multifactorial disorder that can progress to liver fibrosis and cause a worldwide public health concern. Coffee consumption may have a protective impact on NAFLD and liver fibrosis. However, the evidence from the previous studies is inconsistent. This meta-analysis summarizes available literature. MATERIALS AND METHODS This study comprises two meta-analyses. The first meta-analysis summarizes the effect of coffee consumption on NAFLD in those who did or did not drink coffee. The second analysis compares the risk of liver fibrosis development between NAFLD patients who did or did not drink coffee. Pooled risk ratios (RR) and confidence intervals (CI) of observational studies were estimated. RESULTS Of the total collected 321 articles, 11 met our eligibility criteria to be included in the analysis. The risk of NAFLD among those who drank coffee compared to those who did not was significantly lower with a pooled RR value of 0.77 (95% CI 0.60-0.98). Moreover, we also found a significantly reduced risk of liver fibrosis in those who drink coffee than those who did not drink in the NAFLD patients with the relative risk (RR) of 0.68 (95% CI 0.68-0.79). CONCLUSIONS Regular coffee consumption is significantly associated with a reduced risk of NAFLD. It is also significantly associated with decreased risk of liver fibrosis development in already diagnosed NAFLD patients. Although coffee consumption may be considered an essential preventive measure for NAFLD, this subject needs further epidemiological studies.
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Affiliation(s)
- Umar Hayat
- Department of Population Health, University of Kansas School of Medicine, Wichita, KA, USA.
| | - Ali A Siddiqui
- Department of Gastroenterology, Loma Linda University Hospital, Loma Linda, CA, USA
| | - Hayrettin Okut
- Department of Population Health, University of Kansas School of Medicine, Wichita, KA, USA
| | - Saba Afroz
- Hospital Medicine, Wesley Medical Center, Wichita, KA, USA
| | - Syed Tasleem
- Department of Gastroenterology, Baylor College of Medicine, Houston, USA
| | - Ahmed Haris
- Hospital Medicine, Wesley Medical Center, Wichita, KA, USA
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Moussa I, Day RS, Li R, Kaseb A, Jalal PK, Daniel‐MacDougall C, Hatia RI, Abdelhakeem A, Rashid A, Chun YS, Li D, Hassan MM. Association of dietary fat intake and hepatocellular carcinoma among US adults. Cancer Med 2021; 10:7308-7319. [PMID: 34535983 PMCID: PMC8525131 DOI: 10.1002/cam4.4256] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 08/05/2021] [Accepted: 08/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS The role of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) remains unclear. We investigated the associations of total fat and fatty acids with risk of HCC among US adults in a hospital-based case-control study. METHODS We analyzed data from 641 cases and 1034 controls recruited at MD Anderson Cancer Center during 2001-2018. Cases were new patients with a pathologically or radiologically confirmed diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck. Cases and controls were frequency-matched by age and sex. Dietary intake was assessed using a validated food frequency questionnaire. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection. RESULTS Monounsaturated fatty acid (MUFA) intake was inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.49; 95% CI, 0.33-0.72). Total polyunsaturated fatty acid (PUFA) intake was directly associated with HCC risk (highest vs. lowest tertile: OR, 1.82; 95% CI, 1.23-2.70). Omega-6 PUFA was directly associated with HCC risk (highest vs. lowest tertile: OR 2.29; 95% CI, 1.52-3.44). Long-chain omega-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) intake was also inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.50; 95% CI, 0.33-0.70). No association was observed for saturated fat and HCC risk. CONCLUSION Our findings support a direct association of omega-6 PUFA intake with HCC and an inverse association of MUFA and long-chain omega-3 PUFA intake with HCC.
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Affiliation(s)
- Iman Moussa
- Department of Epidemiology, Human Genetics, and Environmental ScienceSchool of Public HealthThe University of Texas Health Science Center at HoustonHoustonTexasUSA
| | - Rena S. Day
- Division of Epidemiology, Human Genetics, & Environmental SciencesSouthwest Center for Occupational and Environmental HealthMichael & Susan Dell Center for Healthy LivingSchool of Public HealthThe University of Texas Health Science Center at HoustonHoustonTexasUSA
| | - Ruosha Li
- Department of Biostatistics and Data ScienceSchool of Public HealthThe University of Texas Health Science Center at HoustonHoustonTexasUSA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Prasun K. Jalal
- Division of Gastroenterology and HepatologyDepartment of MedicineBaylor College of MedicineHoustonTexasUSA
| | | | - Rikita I. Hatia
- Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Ahmed Abdelhakeem
- Department of Internal MedicineBaptist Hospitals of Southeast TexasBeaumontTexasUSA
| | - Asif Rashid
- Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Yun Shin Chun
- Division of SurgeryDepartment of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Donghui Li
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Manal M. Hassan
- Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
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Kuraji R, Sekino S, Kapila Y, Numabe Y. Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis. Periodontol 2000 2021; 87:204-240. [PMID: 34463983 PMCID: PMC8456799 DOI: 10.1111/prd.12387] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan.,Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Satoshi Sekino
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne Kapila
- Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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Shekari S, Khonsha F, Rahmati-Yamchi M, Nejabati HR, Mota A. Vanillic Acid and Non-Alcoholic Fatty Liver Disease: A Focus on AMPK in Adipose and Liver Tissues. Curr Pharm Des 2021; 27:4686-4692. [PMID: 34218773 DOI: 10.2174/1381612827666210701145438] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 05/10/2021] [Indexed: 11/22/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD), a growing health issue around the world, is defined as the presence of steatosis in the liver without any other detectable byproducts such as alcohol consumption which includes a wide spectrum of pathologies, such as steatohepatitis, cirrhosis, and hepatocellular carcinoma. A growing body of evidence indicates that the reduction in the 5' adenosine monophosphate-activated protein kinase (AMPK) activity, which could be activated by the consumption of the drugs, hormones, cytokines, and dietary restriction, is related to some metabolic disorders such as obesity, diabetes, PCOS, and NAFLD. Vanillic acid (VA), as an anti-inflammatory, anti-oxidative, anti-angiogenic and anti-metastatic factor, has protective effects on the liver as in two animal models of liver damage. It reduces serum levels of transaminases, inflammatory cytokines, and the accumulation of collagen in the liver and prevents liver fibrosis. Besides, it decreases body and adipose tissue weight in a mice model of obesity and, similar to the liver tissue, diminishes adipogenesis through the activation of AMPK. It has been reported that VA can target almost all of the metabolic abnormalities of NAFLD, such as hepatic steatosis, inflammation, and hepatic injury, at least partially through the activation of AMPK. Therefore, in this review, we will discuss the possible and hypothetical roles of VA in NAFLD, with a special focus on AMPK.
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Affiliation(s)
- Sepideh Shekari
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Fatemeh Khonsha
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Mohammad Rahmati-Yamchi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Hamid Reza Nejabati
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Ali Mota
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz. Iran
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Zhang Y, Li K, Kong A, Zhou Y, Chen D, Gu J, Shi H. Dysregulation of autophagy acts as a pathogenic mechanism of non-alcoholic fatty liver disease (NAFLD) induced by common environmental pollutants. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2021; 217:112256. [PMID: 33901779 DOI: 10.1016/j.ecoenv.2021.112256] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 04/12/2021] [Accepted: 04/13/2021] [Indexed: 06/12/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been the most common chronic liver disease in the world, including the developing countries. NAFLD is metabolic disease with significant lipid deposition in the hepatocytes of the liver, which is usually associated with oxidative stress, inflammation and fibrogenesis, and insulin resistance. Progressive NAFLD can develop into non-alcoholic steatohepatitis (NASH) or hepatocellular carcinoma. The current evidence proposes that environmental pollutants promote development and progression of NAFLD, and autophagy plays a vital role but is multifactorial affected in NAFLD. In this review, we analyzed on the regulations of common environmental pollutants on autophagy in NAFLD. To clarify the involved roles of autophagy, we discussed the dysregulation of autophagy by environmental pollutants in adipose tissue and gut, and their interactions with liver, as well as epigenetic regulation on autophagy by environmental pollutants. Furthermore, protective roles of potential therapeutic treatments on the multiple-hits of autophagy in NAFLD were descripted.
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Affiliation(s)
- Yao Zhang
- School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212000, China
| | - Kongdong Li
- School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212000, China
| | - Anqi Kong
- School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212000, China
| | - Yang Zhou
- School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212000, China
| | - Dongfeng Chen
- Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Jie Gu
- School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212000, China
| | - Haifeng Shi
- School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212000, China.
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36
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Liu Y, Zou J, Dan L, Zhang R, Feng Q. The efficacy of Qigong exercises for nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e22753. [PMID: 33126313 PMCID: PMC7598830 DOI: 10.1097/md.0000000000022753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world that represents an important public health challenge nowadays. Lifestyle changes and exercise can reduce the development of fatty liver. The aim of this systematic review and meta-analysis is to evaluate the treatment efficacy of Qigong for NAFLD. METHODS A detailed search for articles up to September 2020 will be performed to identify randomized controlled trials for Qigong in NAFLD. The following database will be used: PUBMED, Embase, Web of Science, Cochrane Library, Sino Med, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodicals Database, and Wanfang Databas. Grey literature will be explored and the selection of studies, data extraction and validation will be performed independently by 2 reviewers using predefined selection criteria and quality indicators. Stata V.13.0 and Review manager 5.3 software will be used for data synthesis, sensitivity analysis, subgroup analysis, and risk of bias assessment. We will use the grading of recommendations assessment, development, and evaluation system to assess the quality of evidence. RESULTS This research will provide a quantitative and standardized assessment of the treatment efficacy of Qigong for NAFLD. CONCLUSION This systematic review will generate the latest evidence for determining whether Qigong has a positive treatment effect for NAFLD. REGISTRATION NUMBER INPLASY202090034.
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37
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Her Z, Tan JHL, Lim YS, Tan SY, Chan XY, Tan WWS, Liu M, Yong KSM, Lai F, Ceccarello E, Zheng Z, Fan Y, Chang KTE, Sun L, Chang SC, Chin CL, Lee GH, Dan YY, Chan YS, Lim SG, Chan JKY, Chandy KG, Chen Q. CD4 + T Cells Mediate the Development of Liver Fibrosis in High Fat Diet-Induced NAFLD in Humanized Mice. Front Immunol 2020; 11:580968. [PMID: 33013934 PMCID: PMC7516019 DOI: 10.3389/fimmu.2020.580968] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 08/20/2020] [Indexed: 12/24/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has been on a global rise. While animal models have rendered valuable insights to the pathogenesis of NAFLD, discrepancy with patient data still exists. Since non-alcoholic steatohepatitis (NASH) involves chronic inflammation, and CD4+ T cell infiltration of the liver is characteristic of NASH patients, we established and characterized a humanized mouse model to identify human-specific immune response(s) associated with NAFLD progression. Immunodeficient mice engrafted with human immune cells (HIL mice) were fed with high fat and high calorie (HFHC) or chow diet for 20 weeks. Liver histology and immune profile of HIL mice were analyzed and compared with patient data. HIL mice on HFHC diet developed steatosis, inflammation and fibrosis of the liver. Human CD4+ central and effector memory T cells increased within the liver and in the peripheral blood of our HIL mice, accompanied by marked up-regulation of pro-inflammatory cytokines (IL-17A and IFNγ). In vivo depletion of human CD4+ T cells in HIL mice reduced liver inflammation and fibrosis, but not steatosis. Our results highlight CD4+ memory T cell subsets as important drivers of NAFLD progression from steatosis to fibrosis and provides a humanized mouse model for pre-clinical evaluation of potential therapeutics.
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Affiliation(s)
- Zhisheng Her
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Joel Heng Loong Tan
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Yee-Siang Lim
- Genome Institute of Singapore, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Sue Yee Tan
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Xue Ying Chan
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Wilson Wei Sheng Tan
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Min Liu
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Kylie Su Mei Yong
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Fritz Lai
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Erica Ceccarello
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore.,Programme in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Zhiqiang Zheng
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Yong Fan
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kenneth Tou En Chang
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore
| | - Lei Sun
- Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Shih Chieh Chang
- Laboratory of Molecular Physiology, Infection and Immunity Theme, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Chih-Liang Chin
- Translational Biomarkers, Merck Research Laboratories, MSD, Singapore, Singapore
| | - Guan Huei Lee
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Yock Young Dan
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Yun-Shen Chan
- Genome Institute of Singapore, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Seng Gee Lim
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Jerry Kok Yen Chan
- Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore.,Experimental Fetal Medicine Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - K George Chandy
- Laboratory of Molecular Physiology, Infection and Immunity Theme, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Qingfeng Chen
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore.,Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials. Diagnostics (Basel) 2020; 10:diagnostics10090643. [PMID: 32872090 PMCID: PMC7554942 DOI: 10.3390/diagnostics10090643] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/22/2020] [Accepted: 08/24/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials.
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39
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Sarkar S, Lipworth L, Kabagambe EK, Bian A, Stewart TG, Blot WJ, Ikizler TA, Hung AM. A Description of Risk Factors for Non-alcoholic Fatty Liver Disease in the Southern Community Cohort Study: A Nested Case-Control Study. Front Nutr 2020; 7:71. [PMID: 32671089 PMCID: PMC7326146 DOI: 10.3389/fnut.2020.00071] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 04/24/2020] [Indexed: 01/01/2023] Open
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and hypercholesterolemia. In addition, total fat and folate intake have been associated with NAFLD. Aims: We investigated risk factors for NAFLD among individuals of largely low socioeconomic status, and whether these associations differed by race. Methods: A nested case-control study was conducted within the Southern Community Cohort Study. Through linkage of the cohort with Centers for Medicare and Medicaid Services, International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify incident NAFLD cases. Controls were matched 4:1 to cases on enrollment age, sex, and race. A logistic regression was used to estimate odds ratios for the associations of NAFLD with covariates of interest. Results: Neither total fat nor folate intake was significantly associated with NAFLD. Hypercholesterolemia (odds ratio 1.21) and body mass index (75th vs. 25th percentile) for blacks (odds ratio 1.96) and whites (odds ratio 2.33) were associated with an increased risk of non-alcoholic fatty liver disease. No significant interaction with race for any of the studied variables was noted. Conclusions: Both hypercholesterolemia and increasing body mass index, but not total fat and folate intake, were risk factors for NAFLD in the Southern Community Cohort Study.
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Affiliation(s)
- Sudipa Sarkar
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Loren Lipworth
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, United States.,Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Edmond K Kabagambe
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, United States.,Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Aihua Bian
- Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States.,Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Thomas G Stewart
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - William J Blot
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, United States.,International Epidemiology Institute, Rockville, MD, United States
| | - T Alp Ikizler
- Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States.,Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Adriana M Hung
- Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States.,Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
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40
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Han B, Jian Y, Xia X, Hu W, Zhang L, Zhou P. Studying the effects of sea cucumber ovum powder on nonalcoholic fatty liver disease by proteomics techniques in a rat model. Food Funct 2020; 11:6139-6147. [PMID: 32573635 DOI: 10.1039/d0fo00741b] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Sea cucumber is a valuable marine food that has antioxidant, anti-diabetic, and anti-obesity functionalities. Sea cucumber ovum (SCO) may contain functional components, however, it is considered to be a waste product during industrial processing. In order to make good use of SCO, this work investigated the effects of freeze-dried SCO powder on NAFLD, using a rat model, through iBT labeling proteomics techniques, tracking changes in the hepatic protein profiles of rats whose diets were supplemented with SCO powder. Male rats were fed with standard food, a high fat diet (HFD), or a HFD supplemented with 150 mg per kg BW or 450 mg per kg BW SCO powder for 6 weeks. Compared with the HFD, low-dose SCO supplementation in the diet could significantly reduce body weight gain and liver weight. Furthermore, in total, 5922 proteins were identified, and 767 proteins were found to be significantly different proteins (p < 0.05) among all four groups. Most of the significantly different proteins were related to apoptosis and lipid metabolism. Fadd, Dci, and Aif1 have been identified as key proteins in the pathways related to apoptosis, lipid metabolism, and inflammation. The results in this study provide an overview of the SCO-induced changes in the liver proteome of NAFLD, which may help us to understand the molecular mechanism behind the effects of SCO on the alleviation of NAFLD.
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Affiliation(s)
- Binsong Han
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
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41
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Qin M, Yuan F, Ren J, Chi Z. Effectiveness and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: Protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e20699. [PMID: 32569201 PMCID: PMC7310736 DOI: 10.1097/md.0000000000020699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 05/15/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Previous reviews indicate that the effect of Traditional Chinese medicines (TCM) on non-alcoholic fatty liver disease (NAFLD) remains uncertainty. The study results published in the past 8 years may change this situation, but there is no updated systematic review. Therefore, we designed this study to systematically evaluate the effectiveness and safety of TCM in the treatment of NAFLD. METHODS AND ANALYSIS We will search nine online databases from inception to October 01 2019, and the language will not be restricted on included trials. Randomized controlled trials that included patients with NAFLD receiving TCM therapy versus a control group will be included. Two researcher will perform independently the selection of studies, risk of bias assessment and data extraction. We will use the RevMan V.5.2 software with fixed effects model or random effects model according to the heterogeneity test to conduct the data synthesis. We will present the dichotomous data and the continuous data with risk ratios with 95% CIs and weighted mean differences or standardized mean differences with 95% CIs. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to evaluate the evidence quality with low risk, unclear risk, and high risk. RESULTS This study will demonstrate an evidence-based review of TCM for NAFLD. CONCLUSION The study will provide clear evidence to assess the effectiveness and side effects of TCM for NAFLD.
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Affiliation(s)
- Manman Qin
- Jiangxi University of Traditional Chinese Medicine, Wanli District, Nanchang, Jiangxi
| | - Fuqiang Yuan
- Jiangxi University of Traditional Chinese Medicine, Wanli District, Nanchang, Jiangxi
| | - Jiankun Ren
- Henan Vocational College of Nursing, Anyang, Henan
| | - Zhenhai Chi
- Department of Acupuncture-Moxibustion, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi China
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Vahedi H, Bavafaetousi N, Zolfaghari P, Yarmohammadi M, Sohrabi MB. Association between serum folate levels and fatty liver disease. CLINICAL NUTRITION EXPERIMENTAL 2020. [DOI: 10.1016/j.yclnex.2019.11.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Allam AS, Salama MM, Nasser HM, Kabiel WAY, Elsayed EH. Comparison between NAFLD fibrosis score and retinoic acid serum level in NAFLD. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-019-0014-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is described by the abnormal accumulation of fats in livers of individuals without significant alcohol intake. It includes a spectrum of diseases from simple steatosis to steatohepatitis (NASH) with fibrosis and cirrhosis. The prevalence of NAFLD is rising in association with increasing obesity worldwide. Retinoic acid (RA), a metabolite of vitamin A, mediates the functions of vitamin A required for growth and development. Also, RA has been shown to reduce adiposity not only in fat cells but also in the liver through increasing triglyceride hydrolysis and fat oxidation. This could put a future trial of preventing NASH and cirrhosis development by vitamin A supplementation. This work aimed to study the role of retinoic acid in NAFLD, whether it can differentiate simple steatosis from NASH and correlate the result with the NAFLD fibrosis score. It is a cross-sectional study done on 180 patients divided into three groups. Group 1 is composed of 80 patients with simple steatosis and normal ALT; group 2 is composed of 80 patients with NASH and high ALT in addition to group 3 with 20 healthy subjects served as a control group. All patients were proven to have fatty liver by ultrasonography. Serum RA was assayed by using enzyme-linked immunosorbent assay (ELISA) technique, and the NAFLD fibrosis score was calculated and compared with the retinoic acid level.
Result
Serum RA level was significantly decreased in the patient groups as compared to the controls; the lowest serum level was observed among the NASH group, followed by the steatosis group. NAFLD fibrosis score was calculated, and it was higher in the NASH group than in the steatosis group. Besides, there was a significant negative correlation between retinoic acid and NAFLD score among the patient groups.
Conclusion
Serum RA level was lower in patients with simple steatosis and NASH. RA had a high statistically significant difference in differentiation between the patient groups and the control group. The results were comparable to the NAFLD fibrosis score. Thus, retinoic acid could be used for diagnosis and accessing the degree of NAFLD.
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Yan T, Yan N, Wang P, Xia Y, Hao H, Wang G, Gonzalez FJ. Herbal drug discovery for the treatment of nonalcoholic fatty liver disease. Acta Pharm Sin B 2020; 10:3-18. [PMID: 31993304 PMCID: PMC6977016 DOI: 10.1016/j.apsb.2019.11.017] [Citation(s) in RCA: 155] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/23/2019] [Accepted: 10/31/2019] [Indexed: 12/11/2022] Open
Abstract
Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease (NAFLD) and its progressive stage, nonalcoholic steatohepatitis (NASH). Traditional herbal medicines (THM) have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and mechanisms. In modern times, NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and progression. THM have garnered increased attention for providing therapeutic candidates for treating NAFLD. In this review, a new model called “multiple organs-multiple hits” is proposed to explain mechanisms of NASH progression. Against this proposed model, the effects and mechanisms of the frequently-studied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed, among which silymarin and berberine are already under U.S. FDA-sanctioned phase 4 clinical studies. Furthermore, experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are discussed. The opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are highlighted. Increasing mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.
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Affiliation(s)
- Tingting Yan
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding authors.
| | - Nana Yan
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Ping Wang
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yangliu Xia
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Guangji Wang
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Frank J. Gonzalez
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding authors.
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Heinks K, De Schutter-Nüsse C, Boekhoff S, Bogusz A, Zhu J, Peng J, Müller HL. Periostin concentrations in childhood-onset craniopharyngioma patients. J Endocrinol Invest 2019; 42:815-824. [PMID: 30474798 DOI: 10.1007/s40618-018-0987-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 11/19/2018] [Indexed: 01/12/2023]
Abstract
PURPOSE Periostin is highly expressed in craniopharyngioma (CP)-associated fibroblasts and has been identified as a marker for non-alcoholic fatty liver disease (NAFLD). Half of CP patients with hypothalamic syndrome develop NAFLD. We hypothesized that periostin concentration is elevated in biological fluids of CP and associated with pathological hepatic parameters, indicating increased risk for NAFLD. METHODS A cross-sectional study on 35 patients with sellar masses (SMP) recruited in the German Childhood Craniopharyngioma Registry (32 CP, 2 xanthogranuloma, 1 pilocytic astrocytoma), three short-statured patients with isolated growth hormone deficiency, five short-statured patients with normal findings in GH-stimulating tests and decreased insulin-like growth factor (IGF)-1 and seven healthy controls. Periostin was measured by Elisa in serum, urine and saliva. RESULTS Periostin serum, urine and saliva concentrations in CP were similar to concentrations of the other groups. Hypothalamic involvement/hypothalamic lesions, degree of obesity as well as hepatic enzymes were not associated with elevated periostin concentrations. Due to low patient numbers with pathological hepatic parameters, missing imaging data on the degree of steatosis hepatis and the lack of histological proof of NAFLD, no definitive conclusions can be drawn from measured periostin concentrations in serum. Interestingly, the subgroup of patients with decreased IGF-1 levels showed elevated concentrations of serum periostin when compared with other groups. CONCLUSIONS In CP, periostin concentrations are not associated with known risk factors for NAFLD such as hepatic and metabolic parameters, obesity and hypothalamic lesions. Accordingly, periostin does not seem to be a suitable marker for NAFLD in CP.
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Affiliation(s)
- K Heinks
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, 26133, Oldenburg, Germany
| | - C De Schutter-Nüsse
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, 26133, Oldenburg, Germany
- European Medical School Oldenburg - Groningen, Carl von Ossietzky University, 26129, Oldenburg, Germany
| | - S Boekhoff
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, 26133, Oldenburg, Germany
| | - A Bogusz
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, 26133, Oldenburg, Germany
- Department of Endocrinology and Diabetology, The Children's Memorial Health Institute, 04-730, Warsaw, Poland
| | - J Zhu
- Department of Gastroenterology, Zhejiang University, Hangzhou, 310003, China
| | - J Peng
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, 26133, Oldenburg, Germany
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - H L Müller
- Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, 26133, Oldenburg, Germany.
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Zhou X, Li Y, Zhang X, Guan YY, Puentes Y, Zhang F, Speliotes EK, Ji L. Independent markers of nonalcoholic fatty liver disease in a gentrifying population-based Chinese cohort. Diabetes Metab Res Rev 2019; 35:e3156. [PMID: 30892820 PMCID: PMC6606362 DOI: 10.1002/dmrr.3156] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 03/15/2019] [Accepted: 03/17/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND Prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in developing countries, but its causes are not known. We aimed to ascertain the prevalence and determinants of NAFLD in a new largely unmedicated population-based cohort from the rapidly gentrifying region of Pinggu, China. METHODS We randomized cluster sampled 4002 Pinggu residents aged 26 to 76 years. Data from 1238 men and 1928 women without significant alcohol drinking or hepatitis virus B or C infection were analysed. NAFLD was defined using a liver-spleen ratio (L/S ratio) ≤1.1 on unenhanced abdominal computed tomography (CT) scanning. RESULTS Of men and women, 26.5% and 20.1%, respectively, had NAFLD. NAFLD prevalence was highest in younger men and older women. In multivariate logistic regression models, higher body mass index, waist circumference, serum triglyceride, alanine transaminase, and haemoglobin A1c independently increased the odds of NAFLD in both men and women separately. Higher annual household income and systolic blood pressure for men and higher serum uric acid and red meat intake and lower physical activity levels for women also independently associated with higher odds of NAFLD. Individuals with L/S ratio ≤1.1 had linearly increasing rates of obesity, diabetes, and metabolic syndrome that paralleled fatty liver increase. CONCLUSIONS NAFLD is common in a gentrifying Chinese population particularly in younger men of high socioeconomic status and older women with sedentary behaviour who eat red meat. Demographic factors add independent risk of NAFLD above traditional metabolic risk factors. A CT L/S ratio of ≤1.1 identifies individuals at high risk of metabolic disease.
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Affiliation(s)
- Xianghai Zhou
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China
| | - Yufeng Li
- Department of Endocrinology and Metabolism, Pinggu Hospital, Beijing, China
| | - Xiuying Zhang
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China
| | - Ying Ying Guan
- Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan
| | - Yindra Puentes
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan
| | - Fang Zhang
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China
| | - Elizabeth K. Speliotes
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan
- Divisions of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China
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Boyle M, Anstee QM. Nonalcoholic Fatty Liver Disease. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:523-546. [DOI: 10.1002/9781119211419.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Szanto KB, Li J, Cordero P, Oben JA. Ethnic differences and heterogeneity in genetic and metabolic makeup contributing to nonalcoholic fatty liver disease. Diabetes Metab Syndr Obes 2019; 12:357-367. [PMID: 30936733 PMCID: PMC6430068 DOI: 10.2147/dmso.s182331] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Obesity is the most prevalent noncommunicable disease in the 21st century, associated with triglyceride deposition in hepatocytes leading to nonalcoholic fatty liver disease (NAFLD). NAFLD is now present in around a third of the world's population. Epidemiological studies have concluded that ethnicity plays a role in complications and treatment response. However, definitive correlations of ethnicity with NAFLD are thoroughly under-reported. A comprehensive review was conducted on ethnic variation in NAFLD patients and its potential role as a crucial effector in complications and treatment response. The highest NAFLD prevalence is observed in Hispanic populations, exhibiting a worse disease progression. In contrast, African-Caribbeans exhibit the lowest risk, with less severe steatosis and inflammation, lower levels of triglycerides, and less metabolic derangement, but conversely higher prevalence of insulin resistance. The prevalence of NAFLD in Asian cohorts is under-reported, although reaching epidemic proportions in these populations. The most well-documented NAFLD patient population is that of Caucasian ethnicity, especially from the US. The relative paucity of available literature suggests there is a vital need for more large-scale multi-ethnic clinical cohort studies to determine the incidence of NAFLD within ethnic groups. This would improve therapy and drug development, as well as help identify candidate gene mutations which may differ within the population based on ethnic background.
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Affiliation(s)
- Krisztina B Szanto
- Faculty of Life Sciences and Medicine, School of Medicine, King's College London, London, UK,
- Institute for Liver and Digestive Health, University College London, London, UK,
| | - Jiawei Li
- Institute for Liver and Digestive Health, University College London, London, UK,
- Institute of Child Health, University College London, London, UK
| | - Paul Cordero
- Institute for Liver and Digestive Health, University College London, London, UK,
| | - Jude A Oben
- Institute for Liver and Digestive Health, University College London, London, UK,
- Department of Gastroenterology and Hepatology, Guy's and St Thomas' Hospital, NHS Foundation Trust, London, UK
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Mansour-Ghanaei F, Joukar F, Mobaraki SN, Mavaddati S, Hassanipour S, Sepehrimanesh M. Prevalence of non-alcoholic fatty liver disease in patients with diabetes mellitus, hyperlipidemia, obesity and polycystic ovary syndrome: A cross-sectional study in north of Iran. Diabetes Metab Syndr 2019; 13:1591-1596. [PMID: 31336526 DOI: 10.1016/j.dsx.2019.03.009] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 03/05/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to describe the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus (DM), hyperlipidemia, obesity and polycystic ovaries syndrome (PCOS). METHODS In a cross-sectional study, 333 patients who had one of the certain diagnosis of DM, hyperlipidemia, obesity or PCOS were enrolled. Information about demographics, anthropometric, nutritional habitude, smoking history, medical history and physical activity were recorded. Liver ultrasound examination and routine biochemistry analysis were performed. RESULTS Among 333 patients with one of the four above-mentioned diseases. 199 patients (59.8%) had NAFLD. Male were more likely to have NAFLD than female (72.8% vs. 50.8% respectively, P < 0.001). About, 80.7% of patients through 41-50 years age had NAFLD. The frequency of abnormal fasting blood glucose, alanine aminotransferase (ALT), triglyceride, and total cholesterol were significantly higher in patients with NAFLD (P < 0.05). Subjects with NAFLD had a higher body mass index than non-NAFLD (33.6 ± 7.9 kg/m2 vs. 31.1 ± 5.0 kg/m2 respectively, P = 0.002). Patients with DM, hyperlipidemia, hypertension, and hypothyroidism were more likely to have NAFLD (P < 0.05). Patients with consumption of supper, high-fat diet, enjoy of eating and smoking were more likely to have NAFLD and patients with fruit and vegetable uptake and physical activity were less likely to have NAFLD (P < 0.05). CONCLUSIONS As most patients with NAFLD are asymptomatic, employed individuals with higher education levels, with a history of smoking and unhealthy diet along with DM, hyperlipidemia, PCOS and obesity seriously have to be followed and educated for lifestyle modification.
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Affiliation(s)
- Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran.
| | - Sahar Najafi Mobaraki
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Soheil Hassanipour
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Masood Sepehrimanesh
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
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Dong R, Yang X, Wang C, Liu K, Liu Z, Ma X, Sun H, Huo X, Fu T, Meng Q. Yangonin protects against non-alcoholic fatty liver disease through farnesoid X receptor. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 53:134-142. [PMID: 30668392 DOI: 10.1016/j.phymed.2018.09.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/21/2018] [Accepted: 09/03/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUD Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. Dyslipidemia, pathoglycemia and insulin resistance are the major risk factors for the development of NAFLD. To date, no effective drug therapies for this condition have been approved. PURPOSE The present study was to investigate the protective effects of yangonin, a kavalactone isolated from Kava, against NAFLD and further elucidate the mechanisms in vivo and in vitro. STUDY DESIGN A high-fat diet (HFD) induced mouse NAFLD model was used with or without yangonin treatment. METHODS The body weight, relative liver weight and serum biochemical indicators were measured. H&E and Oil Red O staining were used to identify the amelioration of the liver histopathological changes. Serum and hepatic triglyceride, free fatty acids and total cholesterol were analyzed. siRNA, quantitative real-time PCR and Western blot assay were used to clarify the mechanisms underlying yangonin protection. RESULTS Yangonin had obvious protective effects against NAFLD via farnesoid X receptor (FXR) activation. Through FXR activation, yangonin attenuated lipid accumulation in the liver via inhibition of hepatic lipogenesis-related protein including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthetase (FAS), acetyl-CoA carboxylase 1 (ACC1) and stearoyl-CoA desaturase 1 (SCD1). Besides, yangonin promoted lipid metabolism through an induction in genes required for lipoprotein lipolysis and fatty acid β-oxidation. Furthermore, yangonin modulated blood glucose homeostasis through regulation of gluconeogenesis-related gene phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and glycogen synthesis-related gene glycogen synthase kinase 3β (GSK3β) and pyruvate dehydrogenase (PDase). Also, yangonin increased insulin sensitivity through upregulating phosphorylation of insulin responsive substrate 1, 2 (IRS-1 and IRS-2). Then, in vivo and in vitro evidence further demonstrated the involvement of FXR activation in yangonin hepatoprotection. CONCLUSIONS Yangonin protects against NAFLD due to its activation of FXR signalling to inhibit hepatic lipogenesis and gluconeogenesis, and to promote lipid metabolism and glycogen synthesis, as well as insulin sensitivity.
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Affiliation(s)
- Renchao Dong
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China
| | - Xiaobo Yang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China
| | - Changyuan Wang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China
| | - Kexin Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China
| | - Zhihao Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China
| | - Xiaodong Ma
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China
| | - Huijun Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China
| | - Xiaokui Huo
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China
| | - Ting Fu
- Pharmacy Department of Affiliated Zhongshan hospital of Dalian University, Dalian, China
| | - Qiang Meng
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China.
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