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"Metabolic dysfunction"

Reply to Correspondence

Reply to correspondence on “Aspirin and HCC risk in MASLD: Nationwide cohort study with genetic risk analysis”
Yang-Hyun Baek
Received January 15, 2026  Accepted January 17, 2026  Published online January 27, 2026  
DOI: https://doi.org/10.3350/cmh.2026.0068    [Accepted]
  • 185 View
  • 12 Download

Editorial

Aspirin for Hepatocellular Carcinoma Prevention in MASLD: How Far Are We Ready to Proceed? : Editorial on “Aspirin and HCC risk in MASLD: Nationwide cohort study with genetic risk analysis”
Yang-Hyun Baek
Received December 29, 2025  Accepted January 5, 2026  Published online January 9, 2026  
DOI: https://doi.org/10.3350/cmh.2025.1482    [Accepted]
  • 413 View
  • 35 Download

Review Article

Treatment Strategies for Patients with HBV Infection Coexisting with HCV or MASLD
Chieh Liu, Yi-Fen Shih, Chun-Jen Liu
Received October 28, 2025  Accepted January 2, 2026  Published online January 9, 2026  
DOI: https://doi.org/10.3350/cmh.2025.1227    [Accepted]
Hepatitis B virus (HBV) remains a major cause of chronic liver diseases, especially in the Asia-Pacific region. In recent decades, coinfection with hepatitis C virus (HCV) and coexistence with metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as significant clinical concerns among HBV-infected subjects. Although global HBV vaccination programs and curative therapies for HCV have led to a marked decline in HBV/HCV coinfection, MASLD is rapidly becoming the predominant comorbidity due to the global surge in metabolic risk factors. HBV/HCV coinfection typically results in more severe liver damage, with unique challenges in antiviral treatment and risk of HBV reactivation post-HCV clearance. In contrast, HBV/MASLD overlap demonstrates complex metabolic-viral interactions that may influence viral replication, hepatitis B surface antigen seroclearance, fibrosis progression, and risk of hepatocellular carcinoma. This review critically compares the epidemiology, clinical outcomes, and management strategies of HBV patients with concurrent HCV or MASLD, while addressing current research gaps and proposing directions for future investigations.
  • 447 View
  • 39 Download

Original Articles

Normal-weight MASLD: 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
Received July 28, 2025  Accepted December 9, 2025  Published online December 12, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0851    [Accepted]
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 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 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.
Result
s: 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 of 0 CMRF ranged from 9.0-26.7% among normal-weight NAFLD, representing the discrepancy between MASLD and NAFLD definitions. Compared with the overweight/obese MASLD, the normal-weight MASLD had increased all-cause mortality (normal-weight vs. overweight/obese, 23.44 and 13.80 per 1000 person-years; p<0.001) but not LREs (2.81 and 2.59 per 1000 person-years; p=0.54) in the HK CDARS cohort.
Conclusions
Normal-weight individuals with NAFLD demonstrated a lower distribution of CMRFs, resulting in the incomplete agreement between historical NAFLD and MASLD.
Ethical Compliance
For all involved cohorts, the study protocols conformed to the ethical guidelines of the 1975 Declaration of Helsinki and were approved by the appropriate clinical research ethics committee and/or institutional review board, which provided either written consent or a waiver of informed consent.

Citations

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  • 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
  • 1,147 View
  • 151 Download
  • Crossref
Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes video
Le Bich Hang Pham, Taeeung Kim, Seoyoung Kim, Yun Seok Kim, Jiyeon Kim, Kyeongseon Kim, Hyeonwoo Lim, Wan Seob Shim, Byoungmo Kim, So-Yeol Yoo, Jae-Young Lee, Murim Choi, Won Kim, Keon Wook Kang, Jeeyeon Lee
Clin Mol Hepatol 2026;32(1):318-338.
Published online November 17, 2025
DOI: https://doi.org/10.3350/cmh.2025.0779
Background/Aims
Ferroptosis, recently emerged as a new cell death modality characterized by iron-dependent peroxidation of lipids, has been explored in various diseases. However, detection of ferroptosis, particularly in chronic liver disease models, is hampered by the lack of universal ferroptosis markers and limited number of fluorescence sensors for in vivo ferroptosis.
Methods
In this study, we developed TTM-4 as a highly sensitive near-infrared (NIR) fluorescent probe to detect ferroptosis.
Result
s: TTM-4 exhibited turn-on fluorescence upon viscosity change, enabling visualization of lipid peroxidation (LPO) in ferroptotic hepatocytes and liver tissue samples with greater sensitivity than BODIPY 581/591 C11. Timelapse live-cell imaging of erastin-treated cells revealed real-time LPO dynamics involving cytosolic lipid droplets (cLDs), endoplasmic reticulum, and nuclear LDs in a chronological order. Further gene expression analysis of 216 liver tissue samples from the NCBI GEO database showed a significant increase in CIDEC concurrent with TTM-4 fluorescence during progression to metabolic dysfunction-associated steatotic hepatitis (MASH). TTM-4, with its low toxicity and turn-on NIR emission during ferroptosis, also enabled in vivo visualization of ferroptosis in liver injury and metabolic dysfunction-associated steatotic liver disease (MASLD) models.
Conclusions
Our findings suggest that TTM-4 enables monitoring of ferroptosis in MASLD and would aid in early MASH diagnosis.
  • 1,655 View
  • 179 Download
Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement
Joseph Rabbat, Boyu Yang, Hye Won Lee, Huapeng Lin, Emmanuel Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Ming-Hua Zheng, Hannes Hagström, Jérôme Boursier, José Luis Calleja, George Boon-Bee Goh, Wah-Kheong Chan, Rocio Gallego-Durán, Arun J. Sanyal, Victor de Lédinghen, Philip N Newsome, Jian-Gao Fan, Laurent Castéra, Michelle Lai, Céline Fournier-Poizat, Grace Lai-Hung Wong, Mirko Zoncape, Grazia Pennisi, Angelo Armandi, Atsushi Nakajima, Wen-Yue Liu, Ying Shang, Marc de Saint-Loup, Elba Llop, Kevin Kim Jun Teh, Carmen Lara-Romero, Amon Asgharpour, Sara Mahgoub, Mandy Sau-Wai Chan, Clemence M Canivet, Manuel Romero-Gomez, Vincent Wai-Sun Wong, Seung Up Kim, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2026;32(1):289-304.
Published online November 11, 2025
DOI: https://doi.org/10.3350/cmh.2025.0888
Background/Aims
Current guidelines recommend a 2-step approach for identifying advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), using Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE). However, some patients may exhibit discordant results. This study evaluates the histological severity and outcomes in patients with discordant FIB-4 and LSM results.
Methods
This secondary analysis of the VCTE-Prognosis study included 12,950 patients evaluated for MASLD at 16 tertiary centers, of whom 2,915 underwent liver biopsy. Patients were categorized into four groups based on established FIB-4 (1.3) and LSM (8 kPa) cutoffs.
Result
s: F3–F4 fibrosis was observed in 6.4%, 13.7%, 30.6%, and 62.4% in low-FIB-4-low-LSM (n=6,403), high-FIB-4-low-LSM (n=3,017), low-FIB-4-high-LSM (n=1,363), and high-FIB-4-high-LSM (n=2,167) groups, respectively. During a median follow-up of 47.4 months, 248 patients experienced hepatic decompensation, hepatocellular carcinoma, liver transplantation, or liver-related death. The incidence rates of liver-related events (LREs) were 0.67, 1.19, 2.58, and 21.30 per 1,000 person-years, respectively. Compared to low-FIB-4-low-LSM patients, those with low-FIB-4-high-LSM (adjusted subdistribution hazard ratio [aSHR] 4.12) and high-FIB-4-high-LSM (aSHR 21.38) had a significantly higher risk of LREs, while high-FIB-4-low-LSM patients did not. Similar findings were observed when hepatic decompensation and hepatocellular carcinoma were analyzed separately.
Conclusions
Approximately 30% of patients in tertiary centers exhibit discordant FIB-4 and LSM results, with LSM more likely reflecting true severity. While some patients with discordant results may have advanced fibrosis, the overall incidence of LREs remains low.
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Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease
Eileen L. Yoon, Jeong-Yeon Cho, Huiyul Park, Mimi Kim, Ji-Hyeon Park, Hye-Lin Kim, Dae Won Jun
Clin Mol Hepatol 2026;32(1):276-288.
Published online November 3, 2025
DOI: https://doi.org/10.3350/cmh.2025.0796
Background/Aims
The first metabolic dysfunction-associated steatotic liver disease (MASLD) drug was approved with an unsatisfactorily small effect size. This study aimed to determine key factors impacting the cost-effectiveness of a new hypothetical MASLD drug as well as its treatment efficacy.
Methods
A Markov model reflecting the natural history of MASLD was developed, incorporating fibrosis progression, cardiovascular disease risk, and mortality. Treatment effect of drug X (with $20,000 of annual cost) was assumed to achieve a ≥1 stage fibrosis regression, with a 25% gap of effect size in regression rate over non-treatment in the first year. The incremental cost-effectiveness ratio (ICER) over a 20-year horizon was estimated. And sensitivity analyses were conducted to explore uncertainty and identify influential factors.
Result
s: In the base case analysis, drug X provided an incremental gain of 1.32 quality-adjusted life years (QALYs) and 1.20 life years compared to the non-treatment, with an ICER of $68,010/QALY–below the $100,000/QALY willingnessto- pay threshold, indicating that drug X treatment is cost-effective. Two-way sensitivity analysis further highlighted that the drug should achieve at least a 15% initial regression gap and maintain a minimum 3% sustained durability gap to remain cost-effective. In addition baseline fibrosis stage distribution also acted as an influencing factor.
Conclusions
Long-term sustained durability of the hypothetical drug, patient distribution based on baseline fibrosis stage, as well as initial treatment response rate are key factors that influence the cost-effectiveness of new MASLD drugs.
  • 1,083 View
  • 111 Download
Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host–microbe signaling and highlights 2-hydroxyisocaproate as a potential effector
Jiyi Choi, Moon Gyeong Yoon, Se Ha Jang, Geum Ok Baek, Hyun Sun Jung, Na-Rae Lee, Choong Hwan Lee, Ji Eun Han, Jae Youn Cheong, Jung Woo Eun, Soon Sun Kim
Clin Mol Hepatol 2026;32(1):239-257.
Published online October 27, 2025
DOI: https://doi.org/10.3350/cmh.2025.0475
Background/Aims
Gut microbiome plays a pivotal role in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, yet, associated functional mechanisms and host responses of specific microbial species remain insufficiently characterized. This study investigated the Bacteroides eggerthii therapeutic effects on MASLD by integrating multi-omics analysis and experimental validation in a Western diet (WD)-induced mouse model.
Methods
Candidate strains were identified using 16S rRNA gene sequencing of fecal samples from individuals with and without MASLD or obesity. B. eggerthii, a species significantly depleted in both groups, was selected for functional evaluation. Male C57BL/6J mice were fed a WD or WD supplemented with B. eggerthii (WD+B) for 12 weeks. Liver histology, serum biochemistry, fecal microbiome and metabolome profiling, and hepatic and intestinal transcriptomic analyses were performed. Anti-steatotic effects of B. eggerthii–derived metabolites were validated in vitro.
Result
s: Bacteroides eggerthii supplementation significantly improved liver weight, inflammation, fibrosis, and steatosis in WD+B group compared to WD alone. PICRUSt-based LEfSe analysis revealed choloylglycine hydrolase activity enrichment in gut microbiota, and strain-specific qPCR confirmed colonization in mouse colon. Integrated transcriptomic analyses revealed lipid and bile acid signaling pathway restoration, including CD36, FXR, and FGF15. Untargeted metabolomics identified elevated 2-hydroxyisocaproic acid (HICA) as a strain-derived metabolite in feces and B. eggerthii culture supernatants. In vitro, HICA significantly reduced lipid accumulation in free fatty acid-induced steatosis models.
Conclusions
Bacteroides eggerthii ameliorates MASLD via gut-liver axis modulation, including bile acid metabolism and hepatic lipid signaling. These underscore its therapeutic potential and highlight HICA as a novel microbiome-derived metabolite with anti-steatotic activity.
  • 2,426 View
  • 391 Download

Correspondences

Correspondence to the editorial “ASB3 degrades the gateway to β-oxidation: on Hepatocytic ASB3 deficiency alleviates MASLD by decreasing ubiquitin-mediated CPT1A”
Dongqin Yang, Yuli Lin, Chunhua Song, Ming Guan
Received September 25, 2025  Accepted September 27, 2025  Published online September 29, 2025  
DOI: https://doi.org/10.3350/cmh.2025.1100    [Accepted]
  • 942 View
  • 56 Download
Correspondence to the editorial on “Targeting the ASB3-CPT1A axis—a new player in combating metabolic dysfunction-associated steatotic liver disease (CHM-2025-1013)”
Yuli Lin, Dongqin Yang, Zhihao Wu, Ming Guan, Chunhua Song
Received September 23, 2025  Accepted September 27, 2025  Published online September 29, 2025  
DOI: https://doi.org/10.3350/cmh.2025.1086    [Accepted]
  • 799 View
  • 35 Download

Editorial

Targeting the ASB3-CPT1A axis—a new player in combating metabolic dysfunction-associated steatotic liver disease
Yueying Yang, Ying Yang, Yan Lu
Received September 8, 2025  Accepted September 8, 2025  Published online September 15, 2025  
DOI: https://doi.org/10.3350/cmh.2025.1013    [Accepted]
  • 1,267 View
  • 58 Download

Review

Pediatric metabolic dysfunction–associated steatotic liver disease and the gut microbiome: from research landscape to targeted modulation
Lu Jiang, Lan-Duoduo Du, Jing Zeng, Hui-Kuan Chu, Zhong Peng, Jian-Gao Fan
Clin Mol Hepatol 2026;32(1):53-68.
Published online August 19, 2025
DOI: https://doi.org/10.3350/cmh.2025.0718
Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, has become the most common form of chronic liver disease in children. The spectrum of pediatric MASLD ranges from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and in rare cases, hepatocellular carcinoma. Its pathogenesis involves a complex interplay among genetic, epigenetic, and environmental factors, along with alterations in the gut microbiota and its associated metabolites. Given the staggering prevalence and the distinct etiopathogenesis of pediatric MASLD, characterization of the gut microbiota and microbial products could facilitate the development of diagnostic tools and inform targeted therapeutic strategies. Current research on the gut microbiome in the context of pediatric MASLD is limited by small sample size, inadequate use of liver biopsy, methodological inconsistencies in sequencing, and confounding effects from metabolic comorbidities. In this review, we summarize clinical studies on alterations in the gut microbiota and microbial products (short-chain fatty acids, bile acids, and ethanol) that impact the pathogenesis of pediatric MASLD. We discuss the therapeutic potential of dietary modification, pharmacological treatments, and probiotics in improving disease progression by summarizing current clinical studies. Enhancing our understanding of the gut-liver axis may aid in the development of effective therapeutic strategies for pediatric MASLD.
  • 5,369 View
  • 240 Download

Letter to the Editor

Comment on “High Steatosis-Associated Fibrosis Estimator Scores Predict Hepatocellular Carcinoma in Viral and Non-Viral Hepatitis and Metabolic Dysfunction-Associated Steatotic Liver Disease”
Prajnasini Satapathy, Rachana Mehta, Ranjana Sah
Received August 2, 2025  Accepted August 6, 2025  Published online August 8, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0875    [Accepted]
  • 2,821 View
  • 23 Download

Original Article

Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A
Yuli Lin, Wulei Hou, Mengxiao Ge, Zhihao Wu, Linlin Huang, Haoye Liu, Wenli Zhang, Xiyu Deng, Lanxin Wang, Ming Guan, Chunhua Song, Zuoyun Wang, Dongqin Yang
Clin Mol Hepatol 2025;31(4):1333-1354.
Published online August 8, 2025
DOI: https://doi.org/10.3350/cmh.2024.1041
Background/Aims
Excessive lipid accumulation in hepatocytes is a critical cause of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Ankyrin repeat and SOCS box protein 3 (ASB3) is an E3 ubiquitin ligase that mediates diverse disease processes; however, the direct substrates of ASB3 in lipid metabolism and its role in MASLD remain unexplored.
Methods
We generated ASB3 knockout mice fed a high-fat diet to induce MASLD. Oxygen consumption and fatty acid oxidation (FAO) were used to assess lipid metabolism. LC-MS/MS and IP were used to verify the ASB3 target protein. Correlation analysis was conducted on the cohort of MASLD patients vs. the control group.
Result
s: Loss of the ASB3 E3 ubiquitin ligase in hepatocytes strengthens mitochondrial FAO, thereby influencing energy consumption to decrease triglyceride storage and lipid accumulation. Quantitative lysine ubiquitination proteomics revealed that ASB3 directly mediated the ubiquitin levels at two sites (K180 and K639) in carnitine palmitoyl transferase 1A (CPT1A), a rate-limiting enzyme of FAO, to induce CPT1A degradation. Moreover, both constitutive and hepatocyte-specific ASB3 knockout enhance FAO and delay lipid accumulation, liver steatosis, and MASLD progression in a CPT1A-dependent manner. Hepatic ASB3 deficiency also delays fibrosis in MASLD. Analysis of public databases and liver tissue samples from MASLD patients revealed that ASB3 was highly expressed in MASLD patients and was negatively correlated with CPT1A.
Conclusions
Our study reveals the key roles of ASB3 in the development of MASLD and suggests a novel therapeutic potential for MASLD.
  • 4,745 View
  • 492 Download

Editorial

GLP-1RA may open a new era for MASLD treatment
Ye Feng, Chengfu Xu
Received June 12, 2025  Accepted June 19, 2025  Published online June 24, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0628    [Accepted]
  • 2,217 View
  • 77 Download

Review

Prospects of Mendelian randomization in hepatology: a comprehensive literature review with practice guidance
Lanlan Chen, Qi Rao, Menghan Gao, Guoyue Lv, Frank Tacke
Clin Mol Hepatol 2025;31(4):1115-1138.
Published online June 9, 2025
DOI: https://doi.org/10.3350/cmh.2025.0541
Mendelian randomization (MR), a powerful statistical tool for causal inference, has been widely applied in various fields of medical research, even extending to economics and psychology. In hepatology, MR has been utilized to identify risk factors and potential therapeutic targets for liver diseases, including metabolic dysfunction-associated steatotic liver disease, cholestatic and autoimmune liver diseases, and hepatobiliary cancer. MR can provide evidence of causation via associations between genetic variants, modifiable exposures and liver disease occurrence or outcomes, using large existing datasets. However, results from MR studies are sometimes scattered, biologically not plausible or even controversial between analyses, potentially reflecting a trend of inappropriate application of this method (e.g., inappropriate selection of genetic instruments, insufficient assessment of horizontal pleiotropy, compromised statistical power, and neglected genetic diversity among different populations), and thus hinder the translation of MR findings from bench to bedside. Assessing these critical issues and pinpointing bona fide evidence are essential but quite challenging for clinicians. In this review, we aim to introduce the MR method to hepatologists and provide a comprehensive overview of the current MR findings that are relevant for hepatologists. Furthermore, we will discuss how to evaluate the quality of MR publications, interpret MR findings, and illustrate good practice of using MR studies in hepatology.

Citations

Citations to this article as recorded by  Crossref logo
  • Childhood Obesity and Age‐Related Diseases: A Systematic Review and Meta‐Analysis of Mendelian Randomization Evidence
    Haoxue Zhu, Xinghao Yi, Mengyu He, Siyi Wu, Ming Li, Shan Gao
    Pediatric Obesity.2026;[Epub]     CrossRef
  • Association of genetically instrumented HMGCR inhibition with the therapeutic role of prostate cancer: a Mendelian randomization study and supporting in vitro experiments
    Xiaojie Hao, Jingjun Mu
    Frontiers in Pharmacology.2026;[Epub]     CrossRef
  • Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis
    Juhee Ahn, Moon Haeng Hur, Hyunjae Shin, Min Kyung Park, Sungho Won, Jeayeon Park, Yunmi Ko, Youngsu Park, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
    Clinical and Molecular Hepatology.2026; 32(1): 339.     CrossRef
  • Helicobacter pylori, peptic ulcer disease, and colorectal cancer: a prospective study with genome-wide interaction analysis and Mendelian randomization
    Ziqi Wan, Jiarui Mi, Xiaoyin Bai, Dong Wu, Sunny Hei Wong
    Infectious Agents and Cancer.2025;[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
  • Integrative genome-wide analysis unveils the genetic landscape of gallstone disease and highlights novel loci with therapeutic potential
    Haotian Chen, Zhengye Liu, Hanze Du, Mixue Zheng, Ziqi Wan, Nan Zhao, Guanqiao Li, Xiaoyin Bai, Dong Wu, Jiarui Mi
    BMJ Open Gastroenterology.2025; 12(1): e001976.     CrossRef
  • 5,004 View
  • 245 Download
  • 4 Web of Science
  • Crossref

Editorial

Risk stratification of metabolic dysfunction-associated steatotic liver disease: The KASL pathway: Editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
May Xuan Goh, Xin En Goh, Jarell Jie-Rae Tan, Vincent L Chen, Yu Jun Wong
Clin Mol Hepatol 2026;32(1):429-431.
Published online April 28, 2025
DOI: https://doi.org/10.3350/cmh.2025.0420

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
    Hye Won Lee, Seung Up Kim
    Clinical and Molecular Hepatology.2026; 32(1): e87.     CrossRef
  • 5,293 View
  • 41 Download
  • Crossref

Original Articles

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).
Result
s: 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

Citations to this article as recorded by  Crossref logo
  • 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;[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
  • 12,381 View
  • 287 Download
  • 4 Web of Science
  • Crossref
HTD1801 demonstrates promising potential for histologic improvements in metabolic dysfunction-associated steatohepatitis in both a preclinical and phase 2 study
Vincent Wai-Sun Wong, Guy W. Neff, Adrian M. Di Bisceglie, Ru Bai, Junwei Cheng, Meng Yu, Alexander Liberman, Liping Liu, Nadege Gunn
Clin Mol Hepatol 2025;31(3):1071-1083.
Published online April 21, 2025
DOI: https://doi.org/10.3350/cmh.2025.0145
Background/Aims
Berberine ursodeoxycholate (HTD1801) has been shown to significantly reduce liver fat content (LFC) in an 18-week, placebo-controlled Phase 2 study in patients with metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus. The purpose of this assessment was to establish proof of concept in liver histologic improvement with HTD1801 treatment based on preclinical and clinical evidence.
Methods
The efficacy of HTD1801 was evaluated in a preclinical MASH/dyslipidemia model (golden hamsters fed a high fat diet, eight/group) after six weeks of daily treatment. Additionally, in a secondary analysis of a Phase 2 clinical study, 100 patients with presumed MASH were evaluated by multiple noninvasive markers associated with MASH resolution and/or fibrosis improvement. These include magnetic resonance imaging proton density fat fraction (MRIPDFF; ≥30% LFC reduction), iron-corrected T1 (≥80 ms reduction), alanine aminotransferase (≥17 U/L reduction), weight loss (≥5% reduction), Fibrosis-4 index (shift to <1.3), and MASH resolution index (achieving ≥–0.67).
Result
s: Preclinical findings in the MASH/dyslipidemia hamster model showed that HTD1801 significantly improved histologic fibrosis and the Nonalcoholic Fatty Liver Disease Activity Score to such a degree that improvements approximated the appearance of the normal controls. In the clinical study, 52% of HTD1801-treated patients achieved MRI response criteria compared to 24% of placebo (p<0.05). Dose-dependent improvements were observed across biomarkers, with more HTD1801-treated patients achieving response criteria associated with improvements in the histologic features of MASH.
Conclusions
These findings suggest that HTD1801 has strong potential to produce histological improvements in patients with MASH.

Citations

Citations to this article as recorded by  Crossref logo
  • Molecular mechanisms and clinical applications of gut microbiota-derived bioactive compounds in metabolic dysfunction-associated fatty liver disease
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Editorial

Metabolic health in antiviral era of chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
Shang-Chin Huang, Jia-Horng Kao
Clin Mol Hepatol 2026;32(1):423-425.
Published online April 11, 2025
DOI: https://doi.org/10.3350/cmh.2025.0369

Citations

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  • Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
    Shang-Chin Huang, Jia-Horng Kao
    Clinical and Molecular Hepatology.2026; 32(1): e117.     CrossRef
  • Correspondence to editorial 1 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
    Rui Huang, Mindie H. Nguyen
    Clinical and Molecular Hepatology.2026; 32(1): e83.     CrossRef
  • 4,420 View
  • 43 Download
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Review

Emerging therapies and real-world application of metabolic dysfunction-associated steatotic liver disease treatment
Hee Yeon Kim, Mary E. Rinella
Clin Mol Hepatol 2025;31(3):753-770.
Published online April 2, 2025
DOI: https://doi.org/10.3350/cmh.2025.0083
Metabolic dysfunction-associated steatotic liver disease, formerly referred to as non-alcoholic fatty liver disease, is the most common liver disease in Western countries and has emerged as the leading indication for liver transplantation. Metabolic dysfunction-associated steatohepatitis (MASH), a more advanced stage, carries a high risk of progression to liver fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Until recently, lifestyle intervention remained the mainstay of MASH management, with no pharmacological treatments specifically approved. However, advances in understanding its pathophysiological mechanisms have fueled numerous clinical trials, culminating in the Food and Drug Administration’s (FDA) approval of resmetirom as the first treatment for MASH in 2024. Additionally, many investigational drugs are nearing FDA approval or progressing through late-stage clinical trials. This review examines the current therapeutic landscape, highlights strategies for identifying patients suitable for liver-directed therapies in real-world settings, and discusses the challenges that remain.

Citations

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  • Quzhou-sourced Fructus Aurantii ameliorates MASLD by modulating glycolysis-dependent M1 polarization in hepatic macrophages
    Junbin Yan, Yunmeng Nie, Menglu Ding, Mi Zhou, Tingyuan Li, Sumei Xu, Shuo Zhang
    Phytomedicine.2026; 150: 157572.     CrossRef
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  • Convergent Metabolic Pathways in MASH Therapeutics: An AMPK‐Centric Analysis
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    Journal of Cellular and Molecular Medicine.2026;[Epub]     CrossRef
  • Steatotic Liver Disease in Older Adults: Clinical Implications and Unmet Needs
    Daniel Clayton-Chubb, William W. Kemp, Ammar Majeed, Peter W. Lange, Jessica A. Fitzpatrick, Karl Vaz, John S. Lubel, Alexander D. Hodge, Joanne Ryan, John J. McNeil, Alice J. Owen, Robyn L. Woods, Stuart K. Roberts
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    Amedeo Lonardo, Ralf Weiskirchen
    Exploration of Drug Science.2025;[Epub]     CrossRef
  • Timosaponin AIII from Anemarrhena asphodeloides binds and inhibits S100A8-mediated neutrophil infiltration and NET formation ameliorates MASH
    Yunfan Bai, Jingxin Ju, Ruishi Xie, Jing Li, Xinyi Zhao, Xiaoxue Fang, Ming Zhu, Xintian Lan, Haoming Luo
    International Immunopharmacology.2025; 166: 115539.     CrossRef
  • Full Active Nanoplatform Restores ROS Homeostasis for Synergistic Therapy of Fatty Liver Disease via Dual Endogenous–Exogenous Pathways
    Ziyi Lin, Peng Xu, Yuehai Xu, Yixin Zheng, Huimin Li, Zixin Chen, Zhe Wang, Shaochen Song, Yuhao Liu, Zhao Yang, Ju Cui, Heyun Shen
    ACS Applied Materials & Interfaces.2025;[Epub]     CrossRef
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    Dingwu Li, Xiang Zhang
    Hepatology Communications.2025;[Epub]     CrossRef
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    Xiao‐Dong Zhou, Yusuf Yilmaz, Mazen Noureddin, Hung N. Luu, Ming‐Hua Zheng
    Alimentary Pharmacology & Therapeutics.2025;[Epub]     CrossRef
  • Combination therapies for metabolic dysfunction-associated steatohepatitis: challenges and opportunities
    Xiao-Dong Zhou, Qiong-Yue Fan, Christopher D Byrne, Giovanni Targher, Mark D Muthiah, Daniel Q Huang, Qin-Fen Chen, Mazen Noureddin, Wenhao Li, Vlad Ratziu, Rohit Loomba, Sven M Francque, Arun J Sanyal, Ming-Hua Zheng
    Gut.2025; : gutjnl-2025-337431.     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”
Weixiong Zhu, Xuefan Zeng, Zengxi Yang, Yusheng Cheng, Wence Zhou
Clin Mol Hepatol 2025;31(3):e252-e253.
Published online February 26, 2025
DOI: https://doi.org/10.3350/cmh.2025.0189
  • 8,595 View
  • 77 Download

Reply to Correspondence

Steatotic liver disease

Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
Yoon-su Ha, Won Kim, Seung-Jin Kim
Clin Mol Hepatol 2025;31(2):e226-e227.
Published online February 13, 2025
DOI: https://doi.org/10.3350/cmh.2025.0128
  • 5,847 View
  • 40 Download

Editorial

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 dysfunction-associated steatotic liver disease”
Ho Soo Chun, Minjong Lee
Clin Mol Hepatol 2026;32(1):368-370.
Published online February 11, 2025
DOI: https://doi.org/10.3350/cmh.2025.0116
  • 5,835 View
  • 40 Download

Snapshot

Interventions targeting the gut-liver axis: A potential treatment strategy for metabolic dysfunction-associated steatotic liver disease
Pingping Jin, Xinyi Lu, Daozhen Chen, Yu Chen
Clin Mol Hepatol 2025;31(3):1100-1102.
Published online February 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.1090

Citations

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  • Scutellaria baicalensis extract prevents metabolic dysfunction-associated steatotic liver disease by modulating the gut-liver axis in high-fat diet mice
    Liting Ma, Yizhu Wang, Tao Ren, Lijia Pan, Xinze Li, Shen Wang, Dihao Li, Meiyu Zhang, Fangtong Li, Fei Zheng, Hao Yue
    Phytochemistry.2026; 243: 114720.     CrossRef
  • Hypertension and Long-Term Adverse Clinical Outcomes in MASLD: Sensitivity Analyses for Unmeasured or Uncontrolled Confounding
    Guiying Gao, Xiuhong Wang, Ruizhe Huang, Jing Cao
    Journal of Hepatology.2026;[Epub]     CrossRef
  • Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease
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  • Probiotic-Derived Strain-Specific Metabolites Ameliorate Metabolic Dysfunction–Associated Steatotic Liver Disease through Modulation of the Gut-Liver Axis
    Sang Jun Yoon, Jieun Choi, Sung-Min Won, Jeong Seok Yu, Hee Young Kim, Hyun Chae Joung, In Gyu Park, Jung A Eom, Sang Hak Han, Do Yup Lee, Ki Tae Suk
    Probiotics and Antimicrobial Proteins.2025;[Epub]     CrossRef
  • From liver to gut: the hidden gastrointestinal impact of pediatric metabolic dysfunction-associated steatotic liver disease
    Gianmario Forcina, Vittoria Frattolillo, Maria De Cesare, Assunta Floriano, Rosamaria Palma, Federica Casamassima, Mario Bartiromo, Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Anna Di Sessa
    Expert Review of Gastroenterology & Hepatology.2025; 19(12): 1329.     CrossRef
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Editorial

Steatotic liver disease

Bridging the gap: The GOLM1-OPN-ABCG5 axis in MASH and gallstone disease: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
Nahee Hwang, Sungsoon Fang
Clin Mol Hepatol 2025;31(2):631-634.
Published online February 3, 2025
DOI: https://doi.org/10.3350/cmh.2025.0066

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  • GOLM1 and bile acid synthesis: Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen
    Clinical and Molecular Hepatology.2025; 31(2): e189.     CrossRef
  • Reply to correspondence 2 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Nahee Hwang, Sungsoon Fang
    Clinical and Molecular Hepatology.2025; 31(2): e228.     CrossRef
  • Hyaluronic Acid Hydrogel Implants for Sustained Release of Oxaliplatin and Resiquimod to Prevent Hepatocellular Carcinoma Recurrence Post‐Radiofrequency Ablation
    Yuezhan Shan, Hongyu Chu, Sheyu Ye, Guofeng Ji, Jiayi Zhao, Xinghui Si, Yumin Zhong, Youmao Tao, Jingwei Shi, Xuedong Fang
    Advanced Science.2025;[Epub]     CrossRef
  • A demethylation chloroisosulochrin and a chromone metabolite from the endophytic fungus Penicilium sp.
    Ke-Liang Chen, Xue Wang, Yang Liu, Yun-Bao Liu
    Journal of Asian Natural Products Research.2025; : 1.     CrossRef
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Correspondence

Steatotic liver disease

Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen
Clin Mol Hepatol 2025;31(2):e186-e188.
Published online January 24, 2025
DOI: https://doi.org/10.3350/cmh.2025.0079

Citations

Citations to this article as recorded by  Crossref logo
  • Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yoon-su Ha, Won Kim, Seung-Jin Kim
    Clinical and Molecular Hepatology.2025; 31(2): e226.     CrossRef
  • 5,638 View
  • 42 Download
  • 1 Web of Science
  • Crossref

Letter to the Editor

What is new in the 2024 Chinese guidelines for fatty liver disease?
Rui-Xu Yang, Vincent Wai-Sun Wong, Jian-Gao Fan
Clin Mol Hepatol 2025;31(3):e239-e246.
Published online January 21, 2025
DOI: https://doi.org/10.3350/cmh.2024.1165
  • 9,878 View
  • 94 Download

Editorial

Steatotic liver disease

Unraveling the role of GOLM1-OPN-ABCG5 axis in MASH: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
Yoon-su Ha, Won Kim, Seung-Jin Kim
Clin Mol Hepatol 2025;31(2):628-630.
Published online January 16, 2025
DOI: https://doi.org/10.3350/cmh.2025.0036

Citations

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  • Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yoon-su Ha, Won Kim, Seung-Jin Kim
    Clinical and Molecular Hepatology.2025; 31(2): e226.     CrossRef
  • Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen
    Clinical and Molecular Hepatology.2025; 31(2): e186.     CrossRef
  • 6,483 View
  • 66 Download
  • 2 Web of Science
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Correspondences

Steatotic liver disease

Correspondence to letter to the editor 1 on “Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study”
Seogsong Jeong, Won Kim, Sang Min Park
Clin Mol Hepatol 2025;31(2):e208-e209.
Published online January 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.1171
  • 6,761 View
  • 40 Download

Steatotic liver disease

Age serves as the silent architect of FIB-4’s precision in unveiling advanced hepatic fibrosis in MASLD with T2DM: Correspondence to letter to the editor on “Diagnostic accuracy of the fibrosis-4 index for advanced liver fibrosis in nonalcoholic fatty liver disease with type 2 diabetes: a systematic review and meta-analysis”
Ji Won Han, Dae Won Jun
Clin Mol Hepatol 2025;31(2):e152-e154.
Published online December 30, 2024
DOI: https://doi.org/10.3350/cmh.2024.1160

Citations

Citations to this article as recorded by  Crossref logo
  • Non-invasive Risk-based Surveillance Strategy for Hepatocellular Carcinoma in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease
    Ji Won Han
    The Korean Journal of Gastroenterology.2026; 86(1): 62.     CrossRef
  • 6,562 View
  • 43 Download
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Editorial

Steatotic liver disease

A leap in the dark: Bariatric surgery for treatment of metabolic dysfunction-associated steatotic liver disease related cirrhosis: Editorial on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
Jing Zeng, Jian-Gao Fan
Clin Mol Hepatol 2025;31(2):610-614.
Published online December 17, 2024
DOI: https://doi.org/10.3350/cmh.2024.1099

Citations

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  • Correspondence to editorial on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
    Nicholas A. Rouillard, Linda Henry, Mindie H. Nguyen
    Clinical and Molecular Hepatology.2025; 31(2): e173.     CrossRef
  • Reply to correspondence on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
    Jing Zeng, Jian-Gao Fan
    Clinical and Molecular Hepatology.2025; 31(2): e218.     CrossRef
  • 7,076 View
  • 51 Download
  • 2 Web of Science
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Original Article

Steatotic liver disease

GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers
Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Xiao-Chen Ma, Chen-He Yi, Bao-Rui Tao, Bo Zhang, Yue Ma, Guo Zhang, Rui Zhang, Yan Geng, Jing Lin, Jin-Hong Chen
Clin Mol Hepatol 2025;31(2):409-425.
Published online December 10, 2024
DOI: https://doi.org/10.3350/cmh.2024.0657
Background/Aims
Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.
Methods
The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.
Result
s: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.
Conclusions
In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Citations

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  • Methylation changes of gallbladder DNA during the formation of gallstones
    Hongyu Xu, Jinlong Hu, Jinshan Liu, Rui Wang, Junbin Peng, Peilin Liu, Jiaming Yao, Baoqiang Cao
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    Dan Jiang, Xiaofeng Zhou, Xiaolong Lu
    Letters in Drug Design & Discovery.2026; : 100274.     CrossRef
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    María Celeste Capitani, Alejo M. Capiglioni, Raúl A. Marinelli, Julieta Marrone
    Scientific Reports.2026;[Epub]     CrossRef
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    Jianjun Wang, Xi Chen, Wei He, Xintao Zeng, Pei Yang, Jianping Gong, Decai Wang
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Reply to correspondence 2 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Nahee Hwang, Sungsoon Fang
    Clinical and Molecular Hepatology.2025; 31(2): e228.     CrossRef
  • Unraveling the role of GOLM1-OPN-ABCG5 axis in MASH: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yoon-su Ha, Won Kim, Seung-Jin Kim
    Clinical and Molecular Hepatology.2025; 31(2): 628.     CrossRef
  • Bridging the gap: The GOLM1-OPN-ABCG5 axis in MASH and gallstone disease: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Nahee Hwang, Sungsoon Fang
    Clinical and Molecular Hepatology.2025; 31(2): 631.     CrossRef
  • Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen
    Clinical and Molecular Hepatology.2025; 31(2): e186.     CrossRef
  • GOLM1 and bile acid synthesis: Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen
    Clinical and Molecular Hepatology.2025; 31(2): e189.     CrossRef
  • Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers”
    Yoon-su Ha, Won Kim, Seung-Jin Kim
    Clinical and Molecular Hepatology.2025; 31(2): e226.     CrossRef
  • 9,523 View
  • 379 Download
  • 9 Web of Science
  • Crossref

Review

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
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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    Zhonghao Jiang, Baolin Qian, Tongjie Xu, Junjie Bai, Wenguang Fu
    ImmunoTargets and Therapy.2025; Volume 14: 719.     CrossRef
  • Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Chao Cui, Shuai Gao, Jingfei Shi, Kai Wang
    Gut and Liver.2025; 19(4): 479.     CrossRef
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    Wenhao Wu, Zebin Hou
    Frontiers in Immunology.2025;[Epub]     CrossRef
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    Luis A. Rodríguez-Rojas, Leticia Bucio-Ortiz, Verónica Souza-Arroyo, María Concepción Gutiérrez-Ruiz, Luis E. Gómez-Quiroz, Roxana U. Miranda-Labra
    Exploration of Digestive Diseases.2025;[Epub]     CrossRef
  • Exploring the interplay between metabolic dysfunction-associated fatty liver disease and gut dysbiosis: Pathophysiology, clinical implications, and emerging therapies
    Said A Al-Busafi, Ahmed Alwassief, Ali Madian, Hassan Atalla, Mohamed Alboraie, Ashraf Elbahrawy, Mohammed Eslam
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Present and Future Perspectives in the Treatment of Liver Fibrosis
    Lucia Cerrito, Linda Galasso, Jacopo Iaccarino, Alessandro Pizzi, Fabrizio Termite, Giorgio Esposto, Raffaele Borriello, Maria Elena Ainora, Antonio Gasbarrini, Maria Assunta Zocco
    Pharmaceuticals.2025; 18(9): 1321.     CrossRef
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    Jianping Zhu, Yuzhen Chen, Yidi Han, Ji Li, Fahrul Nurkolis
    PLOS One.2025; 20(9): e0331303.     CrossRef
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    Leonardo Leal-Mercado, Arturo Panduro, Alexis José-Abrego, Sonia Roman
    International Journal of Molecular Sciences.2025; 26(18): 8977.     CrossRef
  • Probiotic-Derived Strain-Specific Metabolites Ameliorate Metabolic Dysfunction–Associated Steatotic Liver Disease through Modulation of the Gut-Liver Axis
    Sang Jun Yoon, Jieun Choi, Sung-Min Won, Jeong Seok Yu, Hee Young Kim, Hyun Chae Joung, In Gyu Park, Jung A Eom, Sang Hak Han, Do Yup Lee, Ki Tae Suk
    Probiotics and Antimicrobial Proteins.2025;[Epub]     CrossRef
  • Impact of non-alcoholic hepatic steatosis on prognosis and clinical outcomes in gastric cancer patients undergoing laparoscopic distal gastrectomy
    Yi-Fan Zou, Yi-Gang Zhang, Zi-Chu Zhao, Zheng Li, Hong-Da Liu, Qing-Ya Li, Ze-Tian Chen, Cheng-Jun Zhu, Hai-Tao Liu, Ji-Wei Wang, Feng-Yuan Li, Lin-Jun Wang, Dian-Cai Zhang, Li Yang, Hao Xu, Ze-Kuan Xu, Sen Wang
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    Wenjuan Chen, Lifan Zhang, Xinyu Gu, Yafeng Liu, Shujun Zhang, Xinjun Hu, Penghui Li
    Frontiers in Molecular Biosciences.2025;[Epub]     CrossRef
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    Haifeng Wang, Songlin Liu, Yonggang Chen, Weiwei Fang, Ying Cheng, Zhigang Zhang, Haiming Hu, Baifei Hu, Hongtao Liu
    Phytomedicine.2025; 148: 157404.     CrossRef
  • Harnessing Gut Microbiome–Brain–Liver Crosstalk: Novel Therapeutic Strategies for Metabolic Dysfunction‐Associated Steatotic Liver Disease
    Xingtao Zhao, Ruolan Li, Jingdong Zhao, Ruiqi Sun, Shuo Zhang, Qiong Pan, Hongyan Lu, Jin Chai
    Medicine Bulletin.2025; 1(2): 136.     CrossRef
  • Sarcopenia and MASLD: novel insights and the future
    Chang-Hai Liu, Qing-Min Zeng, Won Kim, Seung Up Kim, Zobair M. Younossi, Giovanni Targher, Christopher D. Byrne, Christos S. Mantzoros, Phunchai Charatcharoenwitthaya, Isabelle Anne Leclercq, Manuel Romero-Gómez, Hong Tang, Ming-Hua Zheng
    Nature Reviews Endocrinology.2025;[Epub]     CrossRef
  • Honeysuckle-derived exosome-like nanovesicles ameliorate metabolic-associated fatty liver disease by modulating gut microbiota and its metabolites
    Ping Li, Qingyuan Wu, Yuanhao Zhou, Xiaojuan Hu, Yan Tang, Yuanyuan Wang, Weijiao Fan, Yiyi Shan, Kexin Yu, Jie Wang, Shibing Wang, Xiao Ye, Huiyu Liu, Xiaozhou Mou
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    Bo Li, Tao Ma, Yanjun Jia, Chunfeng Mou, Meng Zeng, Jie Yu, Lin Zou, Xiaoqiang Li, Han Wang
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    Liang Ma, He Wang, Qiuyu Jin, Zhiwen Sun, Shuang Yu, Yang Zhang
    International Journal of General Medicine.2025; Volume 18: 7531.     CrossRef
  • Interindividual variability in gut microbiome mediates the efficacy of resistant starch on MASLD
    Xiaoxue Long, Hui Wang, Yuwei Lu, Xiaojing Gao, Yuanyuan Xiao, Mingliang Zhang, Jingyi Guo, Jingyi Yang, Ruiqi Zhang, Qian Li, Guiyun Zhou, Ruibao Yang, Feng Chen, Qingqing Wu, Liming Sun, Chengshuang Chu, Xuexue Zhu, Zhengjun Wu, Quanlu Ren, Chunping You
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    Gvzalnur Kurban, Xiangjun Chen, Xingyi Jin, Hui Xia, Shaokang Wang, Guiju Sun
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    Amedeo Lonardo, Ralf Weiskirchen
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  • Prebiotic and Probiotic Foods in MASLD: Microbiome-Mediated Therapeutic Strategies
    Cui Beiming, Liu Yujie, Hui-Eun Chang Joyce, Chen Jieying, Xu Jiahang, Teoh Jian-Peng, Loong Ho Chun
    Synthetic Biology and Engineering.2025; 3(4): 10018.     CrossRef
  • The Metabolic Dysfunction–Associated Steatotic Liver Disease–CKD Axis: Intersecting Pathways and Opportunities for Early Intervention
    Sriram Sriperumbuduri, Prathab Balaji Saravanan, Gaurav Gupta, Arun Sanyal
    Kidney International Reports.2025; : 103757.     CrossRef
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Original Article

Steatotic liver disease

Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis
Nicholas A. Rouillard, Scott D. Barnett, Xinrong Zhang, Leslie Kam, Richie Manikat, Ramsey Cheung, Mindie H. Nguyen
Clin Mol Hepatol 2025;31(1):227-239.
Published online November 14, 2024
DOI: https://doi.org/10.3350/cmh.2024.0564
Background/Aims
With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the USA. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.
Methods
Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related and non-liver-related mortality were analyzed.
Result
s: Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; p<0.0001), liver-related (3.3% vs. 14%; p<0.0001), and non-liver-related mortality (22.3% vs. 26.9%; p=0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR]=0.63; p<0.0001), liver-related (aHR=0.24; p<0.0001), and non-liverrelated (aHR=0.81; p=0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR=0.39; p<0.0001) whereas open surgeries were associated with higher overall mortality (aHR=1.24; p=0.022).
Conclusions
Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.

Citations

Citations to this article as recorded by  Crossref logo
  • Differential Characteristics and Survival Outcomes of Patients With Cirrhosis According to Underlying Liver Aetiology
    Yu Shi, Nicholas Chien, Ashley Fong, Vy H. Nguyen, Surya Teja Gudapati, Angela Chau, Sally Tran, Linda Henry, Ramsey Cheung, Changqing Zhao, Minjuan Jin, Mindie H. Nguyen
    Alimentary Pharmacology & Therapeutics.2025; 61(10): 1622.     CrossRef
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    Jing Zeng, Jian-Gao Fan
    Clinical and Molecular Hepatology.2025; 31(2): 610.     CrossRef
  • Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
    Wei Wang, Yating Xie, Ailei Xu
    Clinical and Molecular Hepatology.2025; 31(2): e143.     CrossRef
  • Advancing precision medicine in metabolic dysfunction-associated steatotic liver disease
    Bryan A. Priego-Parra, Rocío Gallego-Durán, Berenice M. Román-Calleja, José Antonio Velarde-Ruiz Velasco, Manuel Romero-Gómez, Jordi Gracia-Sancho
    Trends in Endocrinology & Metabolism.2025; 36(11): 1000.     CrossRef
  • Correspondence to editorial on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
    Nicholas A. Rouillard, Linda Henry, Mindie H. Nguyen
    Clinical and Molecular Hepatology.2025; 31(2): e173.     CrossRef
  • Reply to correspondence on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
    Jing Zeng, Jian-Gao Fan
    Clinical and Molecular Hepatology.2025; 31(2): e218.     CrossRef
  • Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
    Weixiong Zhu, Xuefan Zeng, Zengxi Yang, Yusheng Cheng, Wence Zhou
    Clinical and Molecular Hepatology.2025; 31(3): e252.     CrossRef
  • Association between body roundness index and risks of all-cause and cardiovascular mortality in adults with metabolic dysfunction-associated steatotic liver disease: NHANES 1999–2018
    Yanshan Yi, Li Yang
    Frontiers in Nutrition.2025;[Epub]     CrossRef
  • 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
    Clinical and Molecular Hepatology.2025; 31(3): e247.     CrossRef
  • Efficacy and Safety of Bariatric Surgery in Well-Compensated Liver Cirrhosis: A Systematic Review and a Single-Arm Meta-analysis
    Pandora Fonseca, Leonardo Pereira, João Gabriel Braga, Giovanna Macanhã Scremin, Luísa de Araujo, Julia Alves, Gabriel de França, Pedro Bregion, Rafael Rego, Maria Farias, Victor Ivano
    Obesity Surgery.2025; 35(10): 4246.     CrossRef
  • Metabolic Dysfunction Associated to Steatotic Liver Disease: A Review
    Janna Vanessa Diaz Torres, Vanessa Rocío Villanueva Guerrero, Jennifer Patricia Vargas Gómez, Fredy Javier Pacheco Miranda, Lorena Rocío Orozco Álvarez, Joseph David León Insignares, Marian Mares, Héctor Mario Rodríguez Ortiz, Evelyn Mendoza-Torres
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  • Endoscopic Bariatric Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanistic Insights and Metabolic Implications
    Wissam Ghusn, Mira Sridharan, Rachel Fromer, Muhammet Ozdemir, Madeleine G. Haff, Eric J. Vargas
    Biomedicines.2025; 13(10): 2437.     CrossRef
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Editorial

Steatotic liver disease

Stabilizing hepatic fatty acid oxidation: Editorial on “USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination”
Myeung Gi Choi, Na Young Lee, Ja Hyun Koo
Clin Mol Hepatol 2025;31(2):592-595.
Published online November 6, 2024
DOI: https://doi.org/10.3350/cmh.2024.0971

Citations

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  • Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction
    Wooyoung Choi, Gun Ha Woo, Tae-Hwan Kwon, Jae-Han Jeon
    International Journal of Molecular Sciences.2025; 26(19): 9715.     CrossRef
  • JAB1/CRL4B complex represses PPARG/ACSL5 expression to promote breast tumorigenesis
    Ting Hu, Tianyu Ma, Miaomiao Huo, Jiaxiang Liu, Die Zhang, Yu Li, Jinyuan Chang, Min Zhang, Yinuo Wang, Tianyang Gao, Baowen Yuan, Siqi Wang, Qing Li, Xiaoqi Ma, Jingyao Zhang, Wei Huang, Yan Wang
    Cell Death & Differentiation.2025;[Epub]     CrossRef
  • 7,437 View
  • 125 Download
  • 3 Web of Science
  • Crossref

Review

Steatotic liver disease

Bioactive metabolites: A clue to the link between MASLD and CKD?
Wen-Ying Chen, Jia-Hui Zhang, Li-Li Chen, Christopher D. Byrne, Giovanni Targher, Liang Luo, Yan Ni, Ming-Hua Zheng, Dan-Qin Sun
Clin Mol Hepatol 2025;31(1):56-73.
Published online October 21, 2024
DOI: https://doi.org/10.3350/cmh.2024.0782
Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Citations

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  • Radish Green Extract Attenuates Western Diet-Induced Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice
    Hye-Bin Lee, Yu Ra Lee, Eunjung Lee, Seong Un Jeong, Jae-Hyun Yoon, Miri Park, Yoonsook Kim, Ho-Young Park
    Journal of Agricultural and Food Chemistry.2026; 74(1): 874.     CrossRef
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    Yijing Xin, Hui Ma, Xiang Li, Ruiyang Sun, Luo Fang, Libin Pan
    Toxicology and Applied Pharmacology.2026; 509: 117754.     CrossRef
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    Dario Piatto, Delia De Biasio, Francesco Giustino Cesaro, Gianmario Forcina, Vittoria Frattolillo, Antonio Colucci, Fabio Lamberti, Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Anna Di Sessa
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    Jiang Bai, Lijuan Zhang, Letian He, Yun Zhou
    Frontiers in Nutrition.2025;[Epub]     CrossRef
  • Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review
    Erdenetsogt Dungubat, Kohei Fujikura, Masahiko Kuroda, Toshio Fukusato, Yoshihisa Takahashi
    Nutrients.2025; 17(13): 2211.     CrossRef
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    Lu Lu, Chengting Wu, Juhong Jia, Yuanqin Du, Yujiao Peng, Hongna Huang, Jingjing Huang, Yaobin Nong
    Journal of Chromatography B.2025; 1267: 124784.     CrossRef
  • The transition from NAFLD to MASLD: implications for Diagnosis, Prognosis, and Clinical Management
    Carlo Acierno, Riccardo Nevola, Fannia Barletta, Katarzyna Zielińska, Luca Rinaldi, Ferdinando Carlo Sasso, Caterina Conte, Luigi Elio Adinolfi, Alfredo Caturano
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    Wenhua Bai, Zheng Zhu
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    Shidi Hu, Dongmei Wang, Qingtao Yu, Zhi Chen, Weiguo Lu, Yuan Meng, Xuetao Peng, Lan Liu, Heng Wan, Jie Shen
    Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 4699.     CrossRef
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Correspondence

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
  • 5,735 View
  • 45 Download

Editorial

Steatotic liver disease

Essential tools for assessing advanced fibrosis in metabolic dysfunction-associated steatotic liver disease: 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”
Won Sohn
Clin Mol Hepatol 2025;31(1):277-280.
Published online October 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0823

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 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-analy
    Young Eun Chon, Jung Hwan Yu, Seung Up Kim
    Clinical and Molecular Hepatology.2025; 31(1): e61.     CrossRef
  • Impact of Short-Term Liraglutide Therapy on Non-Invasive Markers of Liver Fibrosis in Patients with MASLD
    Aleksandra Bołdys, Maciej Borówka, Łukasz Bułdak, Bogusław Okopień
    Metabolites.2025; 15(8): 510.     CrossRef
  • Hepatic enhancement and signal intensity analysis on magnetic resonance imaging as prognostic biomarkers in advanced chronic liver disease
    Bogdan-Ioan Stanciu, Marcela Iojiban, Andreea Morariu-Barb, Cosmin Caraiani, Bogdan Procopet, Horia Stefanescu, Monica Lupsor-Platon
    World Journal of Hepatology.2025;[Epub]     CrossRef
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  • 55 Download
  • 4 Web of Science
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Original Article

Steatotic liver disease

USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha Hu, Zhouxiang Wang, Kun Zhu, Hongjie Shi, Fang Qin, Tuo Zhang, Song tian, Yanxiao Ji, Jianqing Zhang, Juanjuan Qin, Zhigang She, Xiaojing Zhang, Peng Zhang, Hongliang Li
Clin Mol Hepatol 2025;31(1):147-165.
Published online October 2, 2024
DOI: https://doi.org/10.3350/cmh.2024.0478
Background/Aims
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Result
s: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Citations

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  • RNF90 promotes hepatic steatosis by degrading CPT1α to suppress fatty acid oxidation
    Feng-Juan Yan, Ning Zhang, Shu-Han Li, Mei-Xin Huang, Meng-Meng Wu, Yu-Jie Yan, Xin Liu, Hao Lei
    Journal of Biological Chemistry.2026; : 111231.     CrossRef
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    Jeysson E. Mejía-Guzmán, Ramón A. Belmont-Hernández, Norberto C. Chávez-Tapia, Misael Uribe, Natalia Nuño-Lámbarri
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  • Stabilizing hepatic fatty acid oxidation: Editorial on “USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination”
    Myeung Gi Choi, Na Young Lee, Ja Hyun Koo
    Clinical and Molecular Hepatology.2025; 31(2): 592.     CrossRef
  • Association Between Visceral Adiposity and the Prediction of Hepatic Steatosis and Fibrosis in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
    Renata Bende, Darius Heredea, Iulia Rațiu, Ioan Sporea, Mirela Dănilă, Roxana Șirli, Alina Popescu, Felix Bende
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    Hao Luo, Chujiao Zhu, Yingying Wang, Yidong Dai, Peng Hao, Haiyan Cai, Wenhui Bai, Zhenge Zhang, Jiale Wan, Youping Zhang, Yun Sun, Ziwei Zhang, Yunzhao Wu, Yuanhui Zhai, Wenxuan Wu, Hu Lei, Hanzhang Xu, Ming He, Yingli Wu
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    Wooyoung Choi, Gun Ha Woo, Tae-Hwan Kwon, Jae-Han Jeon
    International Journal of Molecular Sciences.2025; 26(19): 9715.     CrossRef
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Review

Artificial intelligence, epidemiology, methodology, or others

Roles of X-box binding protein 1 in liver pathogenesis
Jihoon Tak, Yun Seok Kim, Sang Geon Kim
Clin Mol Hepatol 2025;31(1):1-31.
Published online October 2, 2024
DOI: https://doi.org/10.3350/cmh.2024.0441
The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunctionassociated steatotic liver disease (MASLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MASLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.

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Reply to Correspondence

Artificial intelligence, epidemiology, methodology, or others

Reply to correspondence on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”
Tian-Yi Ren, Mohammed Eslam, Jian-Gao Fan
Clin Mol Hepatol 2024;30(4):1039-1041.
Published online September 24, 2024
DOI: https://doi.org/10.3350/cmh.2024.0801
  • 5,665 View
  • 38 Download

Editorial

Steatotic liver disease

Towards unification of liver stiffness measurement cutoffs: 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”
Yangyue Zhang, Vincent Wai-Sun Wong
Clin Mol Hepatol 2025;31(1):264-267.
Published online September 20, 2024
DOI: https://doi.org/10.3350/cmh.2024.0766

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  • Correspondence to editorial on “Optimal cutoffs 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-analys
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Letter to the Editor

Steatotic liver disease

Sex-specific associations of metabolic dysfunction-associated steatotic liver disease with cardiovascular outcomes
Meng-Yuan Miao, Jie-Qiong Lyu, Wei Jiang, Zhong-Yue Liu, Guo-Chong Chen
Clin Mol Hepatol 2025;31(1):e35-e38.
Published online September 20, 2024
DOI: https://doi.org/10.3350/cmh.2024.0719

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  • Sex‐Specific Impact of Metabolic Dysfunction‐Associated Fatty Liver Disease on Incident Cardiovascular Diseases and Mortality
    Mahsa Abbaszadeh, Farhad Hosseinpanah, Maryam Tohidi, Sahar Karimpour Reyhan, Maryam Mahdavi, Majid Valizadeh
    Endocrinology, Diabetes & Metabolism.2025;[Epub]     CrossRef
  • Implication of the Androgen Receptor in Muscle–Liver Crosstalk: An Overlooked Mechanistic Link in Lean-MASLD
    Eleni Myrto Trifylli, Christiana Charalambous, Nikolaos Spiliotopoulos, Nikolaos Papadopoulos, Anastasia Oikonomou, Spilios Manolakopoulos, Melanie Deutsch
    Livers.2025; 5(4): 65.     CrossRef
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Correspondence

Steatotic liver disease

PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
Baokai Sun, Likun Zhuang
Clin Mol Hepatol 2025;31(1):e67-e69.
Published online September 10, 2024
DOI: https://doi.org/10.3350/cmh.2024.0744
  • 4,664 View
  • 93 Download

Editorial

Steatotic liver disease

TM6SF2 and PNPLA3: A potential dynamic duo?: Editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
Andrea Caddeo, Rosellina M. Mancina
Clin Mol Hepatol 2025;31(1):293-296.
Published online August 27, 2024
DOI: https://doi.org/10.3350/cmh.2024.0703

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  • PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
    Baokai Sun, Likun Zhuang
    Clinical and Molecular Hepatology.2025; 31(1): e67.     CrossRef
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Original Article

Steatotic liver disease

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD
Baokai Sun, Xiaoqian Ding, Jie Tan, Jie Zhang, Xueru Chu, Shuimi Zhang, Shousheng Liu, Zhenzhen Zhao, Shiying Xuan, Yongning Xin, Likun Zhuang
Clin Mol Hepatol 2024;30(4):863-882.
Published online July 26, 2024
DOI: https://doi.org/10.3350/cmh.2024.0268
Backgrounds/Aims
Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
Methods
The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC).
Result
s: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice.
Conclusions
The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

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    Baokai Sun, Likun Zhuang
    Clinical and Molecular Hepatology.2025; 31(1): e67.     CrossRef
  • TM6SF2 and PNPLA3: A potential dynamic duo?: Editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
    Andrea Caddeo, Rosellina M. Mancina
    Clinical and Molecular Hepatology.2025; 31(1): 293.     CrossRef
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Editorial

Steatotic liver disease

Incretin-based therapy in the management of metabolic dysfunction-associated steatotic liver disease (MASLD): one piece of the puzzle: Editorial on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis”
Tian-Yi Ren, Mohammed Eslam, Jian-Gao Fan
Clin Mol Hepatol 2024;30(4):649-652.
Published online July 23, 2024
DOI: https://doi.org/10.3350/cmh.2024.0558

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  • AMPK Activation and Lipid Homeostasis Regulation in MASLD: Investigating the Hepatoprotective and Anti‐Inflammatory Effects of Meta‐Capridin Medium‐Chain Triglycerides
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    Yangke Cai, Siyuan Xie, Liyi Xu, Jiamin Chen, Jianting Cai
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  • Reply to correspondence on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”
    Tian-Yi Ren, Mohammed Eslam, Jian-Gao Fan
    Clinical and Molecular Hepatology.2024; 30(4): 1039.     CrossRef
  • Correspondence to editorial on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”
    Hayeon Kim, Min Jeong Park, Myeong Gyu Kim, Kyungim Kim
    Clinical and Molecular Hepatology.2024; 30(4): 989.     CrossRef
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Correspondence

Steatotic liver disease

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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  • Single‑cell RNA sequencing analysis of intrahepatic cholangiocarcinoma reveals SPP1 facilitates disease progression via interaction with CD4+ T cells
    Xian Lin, Huanyan Peng, Ke Liu, Wenqi Chen, Ximing Shao, Chun Ning, Hongchang Li, Dongye Yang
    Oncology Letters.2025; 30(2): 1.     CrossRef
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  • 73 Download
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Editorial

Steatotic liver disease

Ursolic acid: A promising therapeutic agent for metabolic dysfunction-associated steatotic liver disease via inhibition of SPP1-induced Th17 cell differentiation: Editorial on “Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease”
So Jung Kim, Jeongeun Hyun
Clin Mol Hepatol 2024;30(4):709-713.
Published online June 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0412

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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
    Yiyuan Zheng, Zhekun Xiong, Lina Zhao, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Fengbin Liu, Yong Li
    Clinical and Molecular Hepatology.2024; 30(4): 1019.     CrossRef
  • 5,462 View
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