Clinical and Molecular Hepatology

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]

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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]

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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]

Abstract
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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.

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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

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Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes: 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.

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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.

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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.

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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]

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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]

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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]

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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

Abstract
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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.

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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]

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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.

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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]

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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

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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

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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).
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

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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;[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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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

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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

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Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States: Pojsakorn Danpanichkul, Yanfang Pang, Tanuj Mahendru, Primrose Tothanarungroj, Luis Antonio Díaz, Juan Pablo Arab, Pimtawan Jatupornpakdee, Mark D. Muthiah, Kwanjit Duangsonk, Won-Mook Choi, Daniel Q. Huang, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2025;31(3):1058-1070.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0169

Background/Aims
Harmful alcohol use is a substantial contributor to liver diseases, liver cancer, and extrahepatic neoplasms. Patterns of alcohol consumption have shifted over recent decades. This study evaluates trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers in the United States (US) from 2000 to 2021.
Methods
Using the methodological framework of the Global Burden of Disease Study 2021, we analyzed trends in incidence, prevalence, and mortality from ALD and alcohol-attributable cancers in the US.
Result
s: In 2021, there were 28,340 new cases of ALD, 227,730 prevalent cases, and 21,860 deaths attributed to ALD in the US. From 2000 to 2021, ALD incidence, prevalence, and mortality increased by 43%, 36%, and 79%, respectively. The age-standardized incidence and death rate of ALD rose disproportionately among females compared to males. For alcohol-attributable cancers, primary liver cancer, colorectal cancer, and esophageal cancer accounted for the largest share of deaths in 2021. Age-standardized death rates increased significantly for primary liver cancer (annual percent change [APC] 2.21%, 95% confidence interval [CI] 1.70–2.73%) and other pharyngeal cancer (APC 1.35%, 95% CI 1.08–1.62%).
Conclusions
The burden of ALD is substantial and continues to rise in the US, with a particularly notable increase among females. Mortality from alcohol-attributable cancers is also increasing, mainly driven by primary liver cancer and pharyngeal cancer. However, system-wise, gastrointestinal cancer had the highest death attributable to alcohol. These findings highlight the urgent need for public health strategies to tackle ALD, primary liver cancer, and alcoholattributable extrahepatic malignancies.

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Advancing policy and practice in alcohol-associated liver disease and alcohol-attributable cancer: Correspondence to the editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the Unite
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang
Clinical and Molecular Hepatology.2026; 32(1): e96. CrossRef
Rising burden of steatotic liver disease in women of childbearing age and projections to 2035
Youxin Wang, Ruiqiu Chen, Shi Yan Lee, Eunice X.X. Tan, Mark Muthiah, Zhou Yu, Margaret L.P. Teng, Jazleen Leo, Cheng Han Ng, Ashok Choudhury, Daniel Q. Huang
JHEP Reports.2026; 8(1): 101646. CrossRef
MetALD: new insights and unraveling therapeutic potential
Yue Feng, PanShiLi Han, Tao Liu, YanHang Gao
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
Sex Disparity in Major Adverse Liver Outcome and Major Adverse Cardiac Event in Alcohol‐Associated Liver Disease
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Mark D. Muthiah, Suthat Liangpunsakul
Liver International.2025;[Epub] CrossRef
Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2025; 49(11): 2451. CrossRef
Consumo de alcohol y cirrosis en mujeres: un riesgo subestimado
P. Huerta, J.P. Arab, L.A. Díaz
Revista de Gastroenterología de México.2025; 90(4): 509. CrossRef
Alcohol use and cirrhosis in women: An underestimated risk
P. Huerta, J.P. Arab, L.A. Díaz
Revista de Gastroenterología de México (English Edition).2025; 90(4): 509. CrossRef
Etiology of cirrhosis is associated with risk of hepatic decompensation and hepatocellular carcinoma
Michelle Ng, Olgert Bardhi, Krystal Lai, Eden Koo, Sruthi Yekkaluri, Kevin Bass, Guruveer Bhamra, Pojsakorn Danpanichkul, Lisa Quirk, Ju Dong Yang, Jeremy Louissaint, Thomas A. Kerr, Amit G. Singal
BMC Gastroenterology.2025;[Epub] CrossRef
Stable Nationwide Sepsis-Related Mortality Does Not Extend to Individuals with Alcohol-Associated Liver Disease
Pojsakorn Danpanichkul, Kwanjit Duangsonk, Claire S. Faulkner, Supapitch Sirimangklanurak, Tulaton Sodsri, Natchaya Polpichai, Shu-Yen Chan, Yanfang Pang, Omar Y. Mousa, Donghee Kim, Suthat Liangpunsakul, Karn Wijarnpreecha
Digestive Diseases and Sciences.2025;[Epub] CrossRef

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Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease: Hye Won Lee, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim; Clin Mol Hepatol 2025;31(3):1018-1031.
Published online April 4, 2025; DOI: https://doi.org/10.3350/cmh.2024.1183

Background/Aims
Recently, the Korean Association for the Study of the Liver (KASL) introduced a noninvasive test-based approach that uses the fibrosis-4 (FIB-4) index followed by vibration-controlled transient elastography (VCTE) to identify high-risk patients with metabolic-associated steatotic liver disease (MASLD). In this study, the KASL two-step approach was validated by assessing the risk of liver-related event (LRE) development.
Methods
We retrospectively analyzed 8,131 patients with MASLD who underwent VCTE between 2012 and 2020. The index date was defined as the date of the VCTE measurement. Using the KASL two-step approach (FIB-4 index and subsequent VCTE), patients were stratified into four groups (low-, intermediate-low-, intermediate-high-, and high-risk groups). Outcomes, including LREs such as decompensation (DCC) or hepatocellular carcinoma (HCC) were evaluated.
Result
s: During the follow-up (median 46.6 months), 86 (1.1%) patients developed LREs (39 [0.5%] with DCC and 47 [0.6%] with HCC). The KASL two-step approach classified 67.6%, 17.7%, 5.7% and 9.0% of patients in the low-, intermediate-low-, intermediate-high-, and high-risk groups, respectively. The cumulative incidences of LREs increased proportionally according to risk stratification (0.07%, 0.10%, 0.29%, and 1.51% at 3 years and 0.35%, 0.26%, 1.94% and 5.46% at 5 years). The overall accuracy in predicting LREs ranged from 67.7–99.8%. The FIB-4 index and subsequent Agile3+, Agile 4, or FibroScan aspartate aminotransferase scores showed similar predictive abilities compared to the KASL approach.
Conclusions
The KASL two-step approach is an effective and practical method for risk stratification in patients with MASLD, optimizing patient care through early identification of high-risk individuals.

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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.

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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.
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Abstract
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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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Genes & Diseases.2025; : 101932. CrossRef
The Gut-Liver Axis: Molecular Mechanisms and Therapeutic Targeting in Liver Disease
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
Cell Metabolism.2025; 37(12): 2342. CrossRef
Gut microbiota in hepatic encephalopathy: a 3PM-guided three-tier health strategy
Jing Chen, Mingliao Niu, Longjiang Zhang
EPMA Journal.2025;[Epub] CrossRef
An umbrella meta-analysis of microbial therapy on hepatic steatosis, fibrosis, and liver stiffness in metabolic dysfunction-associated steatotic liver disease
Gvzalnur Kurban, Xiangjun Chen, Xingyi Jin, Hui Xia, Shaokang Wang, Guiju Sun
Frontiers in Nutrition.2025;[Epub] CrossRef
Drug treatment of MASH from none to (too) many options?
Amedeo Lonardo, Ralf Weiskirchen
Exploration of Medicine.2025;[Epub] CrossRef
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

13,185 View
451 Download
32 Web of Science
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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.

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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
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 live
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
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Yanshan Yi, Li Yang
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Chi-Kuei Hsu, Po-Yu Huang, Chih-Cheng Lai
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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
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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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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

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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
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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

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Steatotic liver disease

Prevalence of steatotic liver disease and associated fibrosis in the general population: An epidemiological survey: Letter to the editor on “Epidemiology of metabolic dysfunction-associated steatotic liver disease”: Lin Guan, Xinhe Zhang, Shanghao Liu, Xiaolong Qi, Yiling Li; Clin Mol Hepatol 2025;31(2):e145-e148.
Published online October 29, 2024; DOI: https://doi.org/10.3350/cmh.2024.0921

7,691 View
94 Download

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.

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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
Multi-omics reveal the key role of gut microbiota metabolism in adenine-induced chronic kidney disease
Yijing Xin, Hui Ma, Xiang Li, Ruiyang Sun, Luo Fang, Libin Pan
Toxicology and Applied Pharmacology.2026; 509: 117754. CrossRef
Liver-Kidney Crosstalk in Major Pediatric Diseases: Unraveling the Complexities and Clinical Challenges
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
Journal of Clinical Medicine.2025; 14(11): 3911. CrossRef
Altered mitochondrial function: a clue therapeutic strategies between metabolic dysfunction-associated steatotic liver disease and chronic kidney disease?
Jiang Bai, Lijuan Zhang, Letian He, Yun Zhou
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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
Quyu Huazhuo Decoction alleviates non-Alcoholic steatohepatitis via remodeling the gut microbiota and regulating bile acid and short-chain fatty acid metabolism
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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Multiorgan crosstalk in MASLD/MASH: from hepatic pathogenesis to systemic complications
Wenhua Bai, Zheng Zhu
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Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis are Associated with Advanced Cardiovascular-Kidney-Metabolic Syndrome in Chinese and US Populations
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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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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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

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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
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
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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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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.

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Feng-Juan Yan, Ning Zhang, Shu-Han Li, Mei-Xin Huang, Meng-Meng Wu, Yu-Jie Yan, Xin Liu, Hao Lei
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Jeysson E. Mejía-Guzmán, Ramón A. Belmont-Hernández, Norberto C. Chávez-Tapia, Misael Uribe, Natalia Nuño-Lámbarri
International Journal of Molecular Sciences.2025; 26(7): 2959. CrossRef
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Myeung Gi Choi, Na Young Lee, Ja Hyun Koo
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Zhenge Zhang, Wanli Duan, Yixiang Wang, Peng Hao, Linlin Chen, Ziyi Hao, Ming He, Yingli Wu, Hao Luo
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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

Abstract
PDF

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 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

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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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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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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

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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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Steatotic liver disease

Leukocyte telomere shortening in metabolic dysfunction-associated steatotic liver disease and all-cause/cause-specific mortality: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed; Clin Mol Hepatol 2024;30(4):982-986.
Published online August 27, 2024; DOI: https://doi.org/10.3350/cmh.2024.0691

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Hepatology Communications.2025;[Epub] CrossRef

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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 Tm6sf2^167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2^167K 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 Tm6sf2^167K 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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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”
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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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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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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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