Clinical and Molecular Hepatology

"Alcoholic fatty liver"

Original Articles

Outcomes of oral antidiabetic drugs in metabolic dysfunction-associated steatotic liver disease: a nationwide target trial emulation study: Heejoon Jang, Yeonjin Kim, Yoo Kyoung Lim, Dong Hyeon Lee, Sae Kyung Joo, Bo Kyung Koo, Gi-Ae Kim, Woojoo Lee, Stefano Romeo, Won Kim, Innovative Target Exploration of NAFLD (ITEN) consortium; Clin Mol Hepatol 2026;32(2):737-750.
Published online January 6, 2026; DOI: https://doi.org/10.3350/cmh.2025.1006

Background/Aims
Patients with concurrent type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) face elevated cardiovascular risks. However, optimal oral antidiabetic drug (OAD) selection for this population remains unclear.
Methods
Using the Korean National Health Information Database, we conducted a target trial emulation comparing cardiovascular outcomes among patients with T2DM and MASLD (defined by fatty liver index ≥30) who initiated sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas with metformin. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke.
Results
Among 71,071 patients (331,726 person-years), SGLT2 inhibitor users experienced a significantly lower MACE risk compared to sulfonylurea users (adjusted subdistribution hazard ratio [aSHR], 0.44; 95% confidence interval [CI], 0.31–0.62). SGLT2 inhibitors also demonstrated a lower MACE risk compared to thiazolidinediones (aSHR, 0.61; 95% CI, 0.39–0.96) and DPP-4 inhibitors (aSHR, 0.59; 95% CI, 0.42–0.83). Cardiovascular mortality risk was notably reduced with SGLT2 inhibitors compared to sulfonylureas (aSHR, 0.13; 95% CI, 0.03–0.50), thiazolidinediones (aSHR, 0.19; 95% CI, 0.04–0.86), and DPP-4 inhibitors (aSHR, 0.22; 95% CI, 0.06–0.84). Mediation analysis revealed that MASLD regression accounted for 8.7% of the total cardiovascular benefit when comparing SGLT2 inhibitors to sulfonylureas.
Conclusions
In patients with concurrent T2DM and MASLD, SGLT2 inhibitors demonstrated better cardiovascular outcomes compared to other OADs. These findings suggest that SGLT2 inhibitors may be the preferred OAD choice for cardiovascular risk reduction in this high-risk population.

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Longitudinal changes in fatty liver index, genetic susceptibility, and incident atrial fibrillation
Siyang Liu, Houde He, Hualan Chen, Hualin Duan, Ying Sun, Dan Deng, Zihao Gui, Lan Liu, Ningjian Wang, Jie Shen, Heng Wan
Clinica Chimica Acta.2026; 589: 121028. CrossRef

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Normal-weight metabolic dysfunction-associated steatotic liver disease: reclassification, characteristics, and adverse liver outcomes across diverse populations: Sherlot Juan Song, Eileen Laureal Yoon, Vincent Wai-Sun Wong, Ae Jeong Jo, Grace Lai-Hung Wong, Jimmy Che-To Lai, Dae Won Jun, Terry Cheuk-Fung Yip; Clin Mol Hepatol 2026;32(2):646-660.
Published online December 12, 2025; DOI: https://doi.org/10.3350/cmh.2025.0851

Background/Aims
Previous studies have identified a substantial degree of agreement between the non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) populations, but the same notion may not apply to normal-weight patients with a lower cardiometabolic risk burden. This study aims to investigate the cardiometabolic risk factor (CMRF) distributions between normal-weight and overweight/obese MASLD, the agreement between historical NAFLD and MASLD, and to compare the risk of liver-related events (LREs) and all-cause mortality in normal-weight versus overweight or obese MASLD.
Methods
This study included participants with steatotic liver disease (SLD) from five cohorts in China (Hong Kong), South Korea, and the United States. Participants were recruited from settings including both hospitals and communities. Individuals were classified into normal-weight and overweight/obese groups.
Results
This study included 33,793 participants with SLD from five cohorts, of whom 20,893 and 20,701 patients met the diagnosis of NAFLD and MASLD, respectively. Normal-weight patients with NAFLD demonstrated a lower CMRF distribution compared to those with overweight/obese NAFLD. In the community-based cohorts, the proportions with 0 CMRF ranged from 9.0 to 26.7% among normal-weight NAFLD patients, representing the discrepancy between MASLD and NAFLD definitions. Compared with the overweight/obese MASLD, the normalweight MASLD had increased all-cause mortality (normal-weight vs. overweight/obese, 23.44 and 13.80 per 1,000 person-years; P<0.001) but not LREs (2.81 and 2.59 per 1,000 person-years; P=0.54) in the Hong Kong Clinical Data Analysis and Reporting System cohort.
Conclusions
Normal-weight individuals with NAFLD demonstrated a lower distribution of CMRFs, resulting in the incomplete agreement between historical NAFLD and MASLD.

Citations

Citations to this article as recorded by

Challenges in defining MASLD in lean individuals: the impact of the Fatty Liver Index on phenotypic characterisation
Sherlot Juan Song, Yiwei Liu, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Gut.2026; : gutjnl-2026-338216. CrossRef
Beyond BMI: Reassessing the Prevalence of Obesity in Patients With MASLD Under the Lancet Commission Diagnostic Criteria
Ru‐Tao Lin, Ren‐Qiang Zeng, Xu‐Ting Shen, Qin‐Mei Sun, Xin Xin, Jia‐Mei Chen, Yi‐Yang Hu, Qin Feng
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef
Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression
Ludovico Abenavoli, Anna Giulia Loricchio, Ivo Lopez, Domenico Morano, Abdulrahman Ismaiel, Dan Lucian Dumitrascu, Francesco Luzza
Medicina.2026; 62(5): 986. CrossRef
Estimated Body Fat Percentage and Triglyceride‐Glucose Index for Identifying MASLD in Lean Asian Adults: A Cross‐Sectional Analysis
Xiang‐Ran Kong, Ya‐Li Chen, Rui Li, Lu‐Xiang Shang, Sha Sha
The Kaohsiung Journal of Medical Sciences.2026;[Epub] CrossRef

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Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study: Xianhua Mao, Xinrong Zhang, Rongtao Lai, Ka-Shing Cheung, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen; Clin Mol Hepatol 2025;31(3):1084-1099.
Published online April 23, 2025; DOI: https://doi.org/10.3350/cmh.2024.1096

Background/Aims
Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.
Methods
Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan^® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).
Results
In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77.
Conclusions
In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.

Citations

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Tirzepatide versus SGLT2 inhibitors for MASLD: a multi-institutional propensity score-matched cohort study
Jheng-Yan Wu, Yu-Min Lin, Wan-Hsuan Hsu, Ting-Hui Liu, Ya-Wen Tsai, Po-Yu Huang, Min-Hsiang Chuang, Tsung Yu, Chih-Cheng Lai
Hepatology International.2026; 20(2): 292. CrossRef
Impact of newer antihyperglycemic agents on hepatic complications: A systematic review and meta-analysis of data from 5.3 million patients with type 2 diabetes mellitus
Jiwon Yang, Yeongseok Hwang, Jin-Sung Ju, Seungbong Han, Jihyun An, Ju Hyun Shim
Hepatology.2026;[Epub] CrossRef
Association of Semaglutide Treatment With Liver Cirrhosis and Hepatocellular Carcinoma in Type 2 Diabetes: A Population‐Based Cohort Study
Assaf Issachar, Talish Razi, Ilya Borochov, Hadar Duskin Bitan, Ronen Arbel
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef
Early cancer risk reduction after GLP-1RA use: Signal or bias?: Letter to the editor on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic l
Shio-Shin Jean, Chih-Cheng Lai
Clinical and Molecular Hepatology.2026; 32(2): e163. CrossRef
Letter to the editor on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
Chunyan Wang, Xu Han, Yinyan Li
Clinical and Molecular Hepatology.2026; 32(2): e167. CrossRef
Correspondence to letter to the editor 1 on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study
Xianhua Mao, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(2): e231. CrossRef
Correspondence to letter to the editor 2 on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study
Xianhua Mao, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(2): e249. CrossRef
Letter to the editor on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
Xingyu Yao
Clinical and Molecular Hepatology.2026; 32(2): e165. CrossRef
Correspondence to editorial on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
Xianhua Mao, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(2): e219. CrossRef
Reply to correspondence on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
Xingyu Yao
Clinical and Molecular Hepatology.2026; 32(2): e267. CrossRef
GLP-1RA may open a new era for MASLD treatment: Editorial on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target tria
Ye Feng, Chengfu Xu
Clinical and Molecular Hepatology.2026; 32(2): 924. CrossRef
Metabolic Dysfunction‐Associated Steatotic Liver Disease and Obesity: Pathogenesis, Diagnostics, Risk Stratification, and Therapeutic Approach
Beom Kyung Kim
The Kaohsiung Journal of Medical Sciences.2026;[Epub] CrossRef
Secular Trend in Glycaemic Management in Type 2 Diabetes Patients With and Without Cirrhosis Between 2000 and 2023: A Territory‐Wide Cohort Study
Mary Yue Wang, Sherlot Juan Song, Nana Peng, Grace Lai‐Hung Wong, Vincent Wai‐Sun Wong, Jimmy Che‐To Lai, Terry Cheuk‐Fung Yip
Alimentary Pharmacology & Therapeutics.2026;[Epub] CrossRef
GLP-1 receptor agonist–SGLT-2 inhibitor combination and risk of major adverse liver and cardiovascular outcomes in adults with MASLD and type 2 diabetes
Xianhua Mao, Hong Fan, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen
Hepatology.2026;[Epub] CrossRef
Tumor microenvironment and metabolic reprogramming in MASLD-related hepatocellular carcinoma
Vanilla X. Zhang, Tiffany C.-Y. Yu, Yu M. Tsui, Irene O.-L. Ng
Trends in Molecular Medicine.2026;[Epub] CrossRef
Hepatic Events Prevention by Antihyperglycemic Therapies and Intervention Comparisons in Type 2 Diabetes: The HEPATIC-T2DM Network Meta-analysis
Pedro Robson Costa Passos, Rodrigo Motta, Valbert Oliveira Costa Filho, Mariana Macambira Noronha, Roberto Cavalcante Venâncio, Guilherme Grossi Lopes Cançado, Amanda Adler, Jeremy F. Cobbold, Jeremy W. Tomlinson
Diabetes Care.2026; 49(6): 1144. CrossRef
Predictors of Discordance Between Controlled Attenuation Parameter and Magnetic Resonance-Proton Density Fat Fraction in Hepatic Steatosis
Dong Yun Kim, Hyung-Jin Rhee, Beom Kyung Kim
Clinical and Translational Gastroenterology.2026;[Epub] CrossRef
Evaluating causal protective effect of dual GLP-1R/GIPR agonists on MASLD: A Mendelian randomization and colocalization study
Yangke Cai, Siyuan Xie, Liyi Xu, Jiamin Chen, Jianting Cai
European Journal of Pharmacology.2025; 1005: 178088. CrossRef
Impaired Thyroid Hormone Sensitivity is Associated with Increased Risk of Liver Fibrosis in Euthyroid Population: A Cross-Sectional Analysis of NHANES
Xingyu Yao, Kaiwen Xiao, Hein Ko Oo
Hormone and Metabolic Research.2025; 57(09): 511. CrossRef

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Special Issue

Steatotic liver disease

KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025: Won Sohn, Young-Sun Lee, Soon Sun Kim, Jung Hee Kim, Young-Joo Jin, Gi-Ae Kim, Pil Soo Sung, Jeong-Ju Yoo, Young Chang, Eun Joo Lee, Hye Won Lee, Miyoung Choi, Su Jong Yu, Young Kul Jung, Byoung Kuk Jang, on behalf of The Korean Association for the Study of the Liver (KASL); Clin Mol Hepatol 2025;31(Suppl):S1-S31.
Published online February 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0045

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Metabolic dysfunction-associated steatotic liver disease and adverse pregnancy outcomes: a nationwide cohort study
Young Mi Jung, Taesu Kim, Min-Jeong Oh, Dong Hyeon Lee, Geum Joon Cho, Won Kim
Hepatology International.2026; 20(1): 69. CrossRef
Unmasking Kidney Risk in Steatotic Liver Disease: A Call for Metabolic Precision
Chan-Young Jung
Gut and Liver.2026; 20(1): 1. CrossRef
Prognostic value of non-invasive fibrosis assessment scores in predicting mortality among individuals with metabolic dysfunction-associated steatotic liver disease
Lingjie Wu, Shunling Cai, Zhongbin Lin, Ruilie Chen, Yuanfeng Zhang, Xiaobing Gong
BMC Public Health.2026;[Epub] CrossRef
Optimal screening criteria for metabolic dysfunction-associated steatotic liver disease with fibrosis
Byeong Geun Song, Myung Ji Goh, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Dong Hyun Sinn
Annals of Hepatology.2026; 31(2): 102199. CrossRef
Managing Metabolic Dysfunction–Associated Steatotic Liver Disease: Protocol for a Scoping Review of Patient Perceptions, Barriers, and Facilitators
Sikyeong Park, Yu Shin Park, Dahye Hong, Bada Kang
JMIR Research Protocols.2026; 15: e81404. CrossRef
Risk Stratification of Chronic Kidney Disease in Adults Using Noninvasive Fibrosis Tests Based on the American Diabetes Association Algorithm
Chan‐Young Jung, Hye Won Lee, Jung Il Lee, Han Ah Lee, Seung Up Kim
Diabetes, Obesity and Metabolism.2026; 28(6): 5240. CrossRef
Rethinking first-line screening in MASLD beyond the limitations of Fibrosis-4 index: Editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
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Clinical and Molecular Hepatology.2026; 32(2): 921. CrossRef
Metabolic Dysfunction‐Associated Steatotic Liver Disease and Obesity: Pathogenesis, Diagnostics, Risk Stratification, and Therapeutic Approach
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The Kaohsiung Journal of Medical Sciences.2026;[Epub] CrossRef
Metabolic dysfunction-associated steatotic liver disease: On track to become the dominant etiology of hepatocellular carcinoma: Reply to correspondence on “Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-
Jian Xu, Wei Zhang, Guo Wu, Jingdong Li
Clinical and Molecular Hepatology.2026; 32(2): e257. CrossRef
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Journal of Korean Medicine Rehabilitation.2026; 36(2): 85. CrossRef
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Metabolic Dysfunction-Associated Steatotic Liver Disease, Recent Revision of Terminology and Its Implications
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Biomedicine & Pharmacotherapy.2025; 188: 118191. CrossRef
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The Journal of Internal Korean Medicine.2025; 46(2): 303. CrossRef
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Nutrients.2025; 17(13): 2211. CrossRef
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The Journal of Korean Diabetes.2025; 26(3): 172. CrossRef
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Ralf Weiskirchen, Amedeo Lonardo
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European Journal of Medical Research.2025;[Epub] CrossRef
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Scientific Reports.2025;[Epub] CrossRef

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Letter to the Editor

Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”: Chi-Kuei Hsu, Po-Yu Huang, Chih-Cheng Lai; Clin Mol Hepatol 2025;31(3):e247-e248.
Published online February 6, 2025; DOI: https://doi.org/10.3350/cmh.2025.0073

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Original Article

High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease: Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao; Clin Mol Hepatol 2025;31(3):796-809.
Published online January 6, 2025; DOI: https://doi.org/10.3350/cmh.2024.0822

Background/Aims
There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods
Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results
Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0–100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38–10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97–31.30) and MASLD (aSHR 4.23; 95% CI 1.43–12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions
The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.

Citations

Citations to this article as recorded by

HCC predictors in routine practice for patients with chronic liver diseases: Correspondence to editorial on “High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease”
Tung-Hung Su, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e52. CrossRef
Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score?: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated
Michael Kwan-Lung Ko, Loey Lung-Yi Mak
Clinical and Molecular Hepatology.2026; 32(1): 371. CrossRef
Risk stratification for hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic
Ho Soo Chun, Minjong Lee
Clinical and Molecular Hepatology.2026; 32(1): 368. CrossRef
Editorial: Residual HCC Risk After Hepatitis C Cure—Can Polygenic Risk Scores Refine Surveillance?
Heechul Nam, Sung Won Lee
Alimentary Pharmacology & Therapeutics.2026; 63(10): 1427. CrossRef
Absence of steatosis combined with cardiometabolic risk factors confers the highest hepatocellular carcinoma risk in treated chronic hepatitis B
Hung-Wei Wang, Hsueh-Chou Lai, Wei-Fan Hsu, Sheng-Hung Chen, Yi-Chun Kuo, Cheng-Yuan Peng
Annals of Medicine.2026;[Epub] CrossRef
Predictors of Discordance Between Controlled Attenuation Parameter and Magnetic Resonance-Proton Density Fat Fraction in Hepatic Steatosis
Dong Yun Kim, Hyung-Jin Rhee, Beom Kyung Kim
Clinical and Translational Gastroenterology.2026;[Epub] CrossRef

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Editorial

Steatotic liver disease

Vibration-controlled transient elastography in shaping the epidemiology and management of steatotic liver disease: Editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”: Xiao-Dong Zhou, Terry Cheuk-Fung Yip, Daniel Q Huang, Mark Dhinesh Muthiah, Mazen Noureddin, Ming-Hua Zheng; Clin Mol Hepatol 2025;31(2):620-624.
Published online December 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.1131

Citations

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Liver Fibrosis and the Risk of Coronary Artery Disease, Stent Thrombosis, Restenosis and Adverse Clinical Outcomes
Na Tian, Tie Xiao, Tianyi Xia, Hai‐Yang Yuan, Michael D. Shapiro, Gregory Y. H. Lip, Cheng‐Han Fanren, Li‐You Lian, Chen‐Xiao Huang, Yi‐Xuan Wei, Giovanni Targher, Christopher D. Byrne, Cheng‐Lv Hong, Shenghong Ju, Ming‐Hua Zheng
Alimentary Pharmacology & Therapeutics.2026; 63(1): 70. CrossRef
Editorial: Does Metabolic Dysfunction‐Associated Steatotic Liver Disease With Advanced Fibrosis Also Equate to Risk of Advanced Coronary Artery Disease? Authors' Reply
Xiao‐Dong Zhou, Yusuf Yilmaz, Ming‐Hua Zheng
Alimentary Pharmacology & Therapeutics.2026; 63(1): 155. CrossRef
Long-Term Glycemic Control and the Risk of Liver Stiffness Progression and Liver-Related Events in MASLD
Xiao-Dong Zhou, Qin-Fen Chen, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Atsushi Nakajima, Emmanuel Tsochatzis, Jérôme Boursier, Elisabetta Bugianesi, Hannes Hagström, Wah-Kheong Chan, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen,
Clinical Gastroenterology and Hepatology.2026; 24(5): 1332. CrossRef
Progression of Liver Fibrosis and Liver-related Event Risk in Metabolic Dysfunction-associated Steatotic Liver Disease at High Cardiovascular Risk
Xiao-Dong Zhou, Qin-Fen Chen, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Atsushi Nakajima, Emmanuel Tsochatzis, Jérôme Boursier, Elisabetta Bugianesi, Hannes Hagström, Wah-Kheong Chan, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen,
Clinical Gastroenterology and Hepatology.2026;[Epub] CrossRef
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Reviews

Steatotic liver disease

Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease: Huma Saeed, Luis Antonio Díaz, Antonio Gil-Gómez, Jeremy Burton, Jasmohan S. Bajaj, Manuel Romero-Gomez, Marco Arrese, Juan Pablo Arab, Mohammad Qasim Khan; Clin Mol Hepatol 2025;31(Suppl):S94-S111.
Published online November 28, 2024; DOI: https://doi.org/10.3350/cmh.2024.0811

Abstract
PDF

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.

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Viral hepatitis

Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B: Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto; Clin Mol Hepatol 2025;31(Suppl):S182-S195.
Published online November 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0837

Abstract
PDF

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

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Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on “Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis”: Young Eun Chon, Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2025;31(1):e61-e63.
Published online October 15, 2024; DOI: https://doi.org/10.3350/cmh.2024.0878

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Original Article

Steatotic liver disease

Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis: Young Eun Chon, Young-Joo Jin, Jihyun An, Hee Yeon Kim, Miyoung Choi, Dae Won Jun, Mi Na Kim, Ji Won Han, Han Ah Lee, Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2024;30(Suppl):S117-S133.
Published online August 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0392

Background/aims
Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF.
Methods
Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated.
Results
A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80–0.86), 0.83 (0.80–0.86), 0.87 (0.84–0.90), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86–0.92), 0.92 (0.89–0.94), 0.89 (0.86–0.92), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1–7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62–3.8 kPa.
Conclusions
VCTE (7.1–7.9 kPa) and MRE (3.62–3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

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Reply to Correspondence

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Reply to correspondence on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”: Jae Hyun Bae; Clin Mol Hepatol 2024;30(4):1047-1049.
Published online August 19, 2024; DOI: https://doi.org/10.3350/cmh.2024.0666

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Editorial

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Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease outcomes: A call for culturally sensitive interventions: Editorial on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”: Jae Hyun Bae; Clin Mol Hepatol 2024;30(4):665-668.
Published online July 29, 2024; DOI: https://doi.org/10.3350/cmh.2024.0562

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The role of SPP1 in MASLD pathogenesis: Therapeutic insights into ursolic acid’s mechanisms of action: Correspondence to editorial on “Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease”: Yiyuan Zheng, Zhekun Xiong, Lina Zhao, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Fengbin Liu, Yong Li; Clin Mol Hepatol 2024;30(4):1019-1022.
Published online July 8, 2024; DOI: https://doi.org/10.3350/cmh.2024.0471

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Steatotic liver disease

Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease: Yue Wang, Sherlot Juan Song, Yichong Jiang, Jimmy Che-To Lai, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip; Clin Mol Hepatol 2025;31(Suppl):S51-S75.
Published online June 27, 2024; DOI: https://doi.org/10.3350/cmh.2024.0246

Abstract
PDF

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

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Preface
Seung Up Kim
Clinical and Molecular Hepatology.2024; 30(Suppl): S3. CrossRef

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Editorial

Steatotic liver disease

Macrophage ATG16L1: Potential candidate for metabolic dysfunction-associated steatohepatitis treatment: Editorial on “Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy”: Junjie Yu; Clin Mol Hepatol 2024;30(4):721-723.
Published online June 18, 2024; DOI: https://doi.org/10.3350/cmh.2024.0443

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Letters to the Editor

Steatotic liver disease

Changing from NAFLD to MASLD: Cumulative incidence of gallstones between patients with NAFLD and those with MASLD in Asia: Shuhei Fukunaga, Tomoyuki Nakane, Michita Mukasa, Hidetoshi Takedatsu, Takumi Kawaguchi; Clin Mol Hepatol 2024;30(4):959-961.
Published online May 10, 2024; DOI: https://doi.org/10.3350/cmh.2024.0233

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Changing from NAFLD to MASLD: Prevalence and progression of ASCVD risk are similar between NAFLD and MASLD in Asia: Hiroyuki Suzuki, Tsubasa Tsutsumi, Machiko Kawaguchi, Keisuke Amano, Takumi Kawaguchi; Clin Mol Hepatol 2024;30(3):577-579.
Published online March 6, 2024; DOI: https://doi.org/10.3350/cmh.2024.0157

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Similar respiratory function including chronic obstructive pulmonary disease between non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease: Tsubasa Tsutsumi, Dan Nakano, Machiko Kawaguchi, Hirokazu Takahashi, Takumi Kawaguchi; Clin Mol Hepatol 2024;30(2):266-268.
Published online January 30, 2024; DOI: https://doi.org/10.3350/cmh.2024.0028

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Correspondence on Letter regarding “Waiting for the changes after the adoption of steatotic liver disease”: Eileen L. Yoon, Dae Won Jun; Clin Mol Hepatol 2024;30(1):126-128.
Published online November 28, 2023; DOI: https://doi.org/10.3350/cmh.2023.0500

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Special Review

Steatotic liver disease

Waiting for the changes after the adoption of steatotic liver disease: Eileen L. Yoon, Dae Won Jun; Clin Mol Hepatol 2023;29(4):844-850.
Published online September 6, 2023; DOI: https://doi.org/10.3350/cmh.2023.0291

Abstract
PDF

Steatotic liver disease was suggested as an overarching term encompassing various etiologies of hepatic steatosis. Experts from multinational liver societies went through the Delphi process, including four rounds of surveys, and consented to adopt a new nomenclature and definition instead of the conventional nonalcoholic fatty liver disease (NAFLD). This was to improve the understanding of the patients and primary care physicians, with an explanation of the pathophysiology in the name of the disease. Also, it could minimize the stigmatization of patients by using the histological neutral term “steatosis” instead of “fatty”. Herein, we will discuss the changes and continuity between the two nomenclatures, metabolic dysfunction-associated steatotic liver disease (MASLD) and NAFLD, as well as the challenges to MASLD which need to be addressed in future.

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Correspondence

Steatotic liver disease

Correspondence on Letter regarding “Risk factors in nonalcoholic fatty liver disease”: Eileen L. Yoon, Dae Won Jun; Clin Mol Hepatol 2023;29(4):1050-1051.
Published online August 29, 2023; DOI: https://doi.org/10.3350/cmh.2023.0310

Citations

Citations to this article as recorded by

Reply to correspondence on “Prognosis of biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: A sub-analysis of the CLIONE study”
Eileen Laurel Yoon, Dae Won Jun
Clinical and Molecular Hepatology.2024; 30(4): 1033. CrossRef

7,790 View
52 Download
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Special Review

Steatotic liver disease

Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity: Gi-Ae Kim, Joon Ho Moon, Won Kim; Clin Mol Hepatol 2023;29(4):831-843.
Published online August 25, 2023; DOI: https://doi.org/10.3350/cmh.2023.0277

Abstract
PDF

The existing term non-alcoholic fatty liver disease (NAFLD) has raised substantial concerns due to its inherent disadvantages of using exclusionary diagnostic criteria and the stigmatizing word ‘fatty.’ Three pan-national liver associations set out to explore a new nomenclature to replace both NAFLD and its suggested alternative, metabolic (dysfunction)-associated fatty liver disease (MAFLD). They surveyed if a change in nomenclature and/or definition is favored and which nomenclature best communicates disease characteristics and increases awareness. In lieu of NAFLD/MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD) has been chosen, and an umbrella term, steatotic liver disease (SLD), encompassing the whole spectrum of liver disease, has been proposed. It has been suggested that cardiometabolic risk factors should be considered when categorizing SLD patients. Furthermore, a new subcategory, MASLD with increased alcohol intake (MetALD), casts light on a neglected group of patients with moderate or more alcohol consumption. The importance of metabolic dysfunction was acknowledged in this new nomenclature, but the precise contribution of metabolic dysfunction and alcohol consumption to the development and progression of SLD remains unclear. Herein, we review hepatologists’ and endocrinologists’ perspectives on the new nomenclature, along with its possible impact on clinical practice. Although it is premature to predict the settlement of the new nomenclature, this review may help build more evidence for a soft landing of it in the future.

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Editorial

Steatotic liver disease

Lean or Non-obese Nonalcoholic Fatty Liver Disease Patients: Are They Really Lean?: Eugene Han, Yong-ho Lee; Clin Mol Hepatol 2023;29(4):980-983.
Published online August 16, 2023; DOI: https://doi.org/10.3350/cmh.2023.0250

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Original Article

Steatotic liver disease

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity: Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe; Clin Mol Hepatol 2023;29(4):987-1001.
Published online July 5, 2023; DOI: https://doi.org/10.3350/cmh.2023.0035

Background/Aims
To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis.
Methods
This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3^rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography.
Results
Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors.
Conclusions
In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

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Correspondence

Steatotic liver disease

Correspondence on Letter regarding “Non-alcoholic fatty liver disease: Definition and subtypes”: Seul Ki Han, Soon Koo Baik, Moon Young Kim; Clin Mol Hepatol 2023;29(3):817-819.
Published online May 17, 2023; DOI: https://doi.org/10.3350/cmh.2023.0155

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Letter to the Editor

Steatotic liver disease

Letter regarding “Non-alcoholic fatty liver disease: Definition and subtypes”: Seogsong Jeong, Yohwan Lim, Su Kyoung Lee, Hyun Wook Han; Clin Mol Hepatol 2023;29(3):810-811.
Published online May 8, 2023; DOI: https://doi.org/10.3350/cmh.2023.0129

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Original Article

Viral hepatitis

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis: Yu Jun Wong, Vy H. Nguyen, Hwai-I Yang, Jie Li, Michael Huan Le, Wan-Jung Wu, Nicole Xinrong Han, Khi Yung Fong, Elizebeth Chen, Connie Wong, Fajuan Rui, Xiaoming Xu, Qi Xue, Xin Yu Hu, Wei Qiang Leow, George Boon-Bee Goh, Ramsey Cheung, Grace Wong, Vincent Wai-Sun Wong, Ming-Whei Yu, Mindie H. Nguyen; Clin Mol Hepatol 2023;29(3):705-720.
Published online May 8, 2023; DOI: https://doi.org/10.3350/cmh.2023.0004

Background/Aims
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
Methods
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
Results
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
Conclusions
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

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Steatotic liver disease

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Original Article

Steatotic liver disease

Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis: Min Jeong Park, Hayeon Kim, Myeong Gyu Kim, Kyungim Kim; Clin Mol Hepatol 2023;29(3):693-704.
Published online March 9, 2023; DOI: https://doi.org/10.3350/cmh.2022.0330

Background/Aims
Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) and thiazolidinedione (TZD) can improve nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). However, comprehensive research comparing the effects of GLP-1RA and TZD is limited. Thus, this study aimed to compare the effects of GLP-1RA and TZD on NAFLD or NASH through a network meta-analysis.
Methods
The PubMed, Embase, Web of Science, and Scopus databases were searched for randomized controlled trials (RCTs) that explored the efficacy of GLP-1RAs or TZDs in adult patients with NAFLD or NASH. The outcomes were liver biopsy-based (NAFLD activity score [NAS], fibrosis stage, and NASH resolution), noninvasive technique-based (liver fat content on proton magnetic resonance spectroscopy [¹H-MRS] and controlled attenuation parameter [CAP]), biological, and anthropometric indicators. A random effects model was used to calculate the mean difference (MD) and relative risk with 95% confidence interval (CI).
Results
Twenty-five RCTs with 2,237 overweight or obese patients were included. GLP-1RA was significantly superior in reducing liver fat content evaluated using ¹H-MRS (MD –2.42, 95% CI –3.84 to –1.00), body mass index (MD –1.60, 95% CI –2.41 to –0.80), and waist circumference (MD –4.89, 95% CI –8.17 to –1.61) than TZD. In liver biopsy-based evaluation and liver fat content assessment using CAP, GLP-1RA tended to surpass TZD, albeit not significantly. Sensitivity analysis showed consistent results with the main results.
Conclusions
Compared with TZD, GLP-1RA had better effects on liver fat content, body mass index, and waist circumference in overweight or obese patients with NAFLD or NASH.

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Published online March 6, 2023; DOI: https://doi.org/10.3350/cmh.2023.0084

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Steatotic liver disease

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The independent effect of exercise on biopsy proven non-alcoholic fatty liver disease: A systematic review: Young-Joo Jin; Clin Mol Hepatol 2023;29(2):414-416.
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Reviews

Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives: Shang-Chin Huang, Chun-Jen Liu; Clin Mol Hepatol 2023;29(2):320-331.
Published online February 1, 2023; DOI: https://doi.org/10.3350/cmh.2022.0422

Abstract
PDF

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.

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Steatotic liver disease

Noninvasive serum biomarkers for liver steatosis in nonalcoholic fatty liver disease: Current and future developments: Sang Bong Ahn; Clin Mol Hepatol 2023;29(Suppl):S150-S156.
Published online January 25, 2023; DOI: https://doi.org/10.3350/cmh.2022.0362

Abstract
PDF

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of the population worldwide and includes nonalcoholic fatty liver, nonalcoholic steatohepatitis (NASH), and cirrhosis. Since NAFLD-associated diseases begin with steatosis, the early diagnosis of steatosis helps to prevent the progression of NASH and fibrosis. In addition, more convenient and easily diagnosable serum biomarkers are becoming crucial in disease diagnosis. In this report, we summarize the known serum biomarkers for liver steatosis and provide guidance for their application in clinical practice.

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Steatotic liver disease

Nonalcoholic fatty liver disease and non-liver comorbidities: Richie Manikat, Mindie H. Nguyen; Clin Mol Hepatol 2023;29(Suppl):s86-s102.
Published online January 5, 2023; DOI: https://doi.org/10.3350/cmh.2022.0442

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

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Steatotic liver disease

Non-alcoholic fatty liver disease: Definition and subtypes: Seul Ki Han, Soon Koo Baik, Moon Young Kim; Clin Mol Hepatol 2023;29(suppl):S5-S16.
Published online December 28, 2022; DOI: https://doi.org/10.3350/cmh.2022.0424

Abstract
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.

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Steatotic liver disease

The effects of moderate alcohol consumption on non-alcoholic fatty liver disease: Hyunwoo Oh, Won Sohn, Yong Kyun Cho; Clin Mol Hepatol 2023;29(Suppl):S261-S267.
Published online December 22, 2022; DOI: https://doi.org/10.3350/cmh.2022.0393

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) is accepted as a counterpart to alcohol-related liver disease because it is defined as hepatic steatosis without excessive use of alcohol. However, the definition of moderate alcohol consumption, as well as whether moderate alcohol consumption is beneficial or detrimental, remains controversial. In this review, the findings of clinical studies to date with high-quality evidence regarding the effects of moderate alcohol consumption in NAFLD patients were compared and summarized.

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Steatotic liver disease

Pharmacological advances in the treatment of nonalcoholic fatty liver diseases : focused on global results of randomized controlled trials: Jihyun An, Joo Hyun Sohn; Clin Mol Hepatol 2023;29(Suppl):S268-S275.
Published online December 20, 2022; DOI: https://doi.org/10.3350/cmh.2022.0437

Abstract
PDF

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease globally, and its prevalence is rapidly increasing. Nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD, is characterized by hepatocellular injury, inflammation, and fibrosis. Patients with NASH or severe fibrosis should be treated according to international NAFLD guidelines. Currently, regulatory agencies have not approved any pharmaceutical treatment for NAFLD. Vitamin E and pioglitazone are efficacious for NASH resolution; however, their benefits must be weighed against the reported risks. In a phase 2 trial, a glucagon-like peptide-1 agonist commonly used for diabetes and obesity was found to improve liver histology in patients with NASH. Furthermore, therapeutic agents targeting NASH pathogenesis, including bile acid signaling, insulin resistance, and lipid metabolism, are in various phases of clinical development. In this article, we review the benefits and drawbacks of current pharmacotherapy and the efficacy of upcoming treatments for NASH.

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