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"Steatotic liver disease"

Original Article

Transitions from Combustible to Noncombustible Tobacco Use and Liver Outcomes in Steatotic Liver Disease
Eun Seok Kang, Su Kyoung Lee, Meng Sha, Stefano Romeo, Seogsong Jeong, Won Kim
Received March 19, 2026  Accepted June 18, 2026  Published online June 25, 2026  
DOI: https://doi.org/10.3350/cmh.2026.0339    [Accepted]
Background/Aims
In adults with steatotic liver disease (SLD), the hepatic impact of transitioning between combustible cigarettes (CCs) and noncombustible nicotine or tobacco products (NNTPs) remains unclear. We examined CC-NNTP transitions and liver-related events (LREs).
Methods
From the Korean National Health Insurance Service, 502,198 adults with SLD and at least one cardiometabolic risk factor completing health screenings during both 2012-2013 and 2019-2020 were followed through December 2023. Seven mutually exclusive groups were defined by CC status and NNTP use; the primary outcome was LRE, including hepatocellular carcinoma and liver cirrhosis. Cox proportional hazards regression, propensity-score matching (PSM), and counterfactual mediation analysis were performed.
Results
Among 502,198 participants (mean age 57.9 years; 65.6% male), 2,549 LREs occurred over a median 3.0-year follow-up. Compared with never-smokers, continuous CC smokers without NNTP use had the highest LRE risk (aHR, 1.51; 95% confidence interval (CI), 1.34-1.70), followed by CC initiators (1.45; 1.17-1.79) and CC quitters (1.28; 1.12-1.46) without NNTPs. CC quitters with NNTP use showed a lower LRE risk than continuous CC smokers without NNTP use in the full cohort (aHR, 0.65; 95% CI, 0.43-0.99), but this association was not statistically significant under PSM (aHR, 0.65; 95% CI, 0.39-1.09). Within-group PSM of NNTP versus nonuse was nonsignificant across all CC categories.
Conclusions
CC cessation was associated with lower LRE risk than continued CC smoking, even among those who transitioned to NNTPs. However, NNTP use showed no independent protective association, supporting complete tobacco/nicotine abstinence as the preferred goal.
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Review Article

Adopting AI-assisted digital pathology imaging analysis in MASH histology assessments
Daniel Yan Zheng Lim, Wei Qiang Leow, Daniela S. Allende, Wah-Kheong Chan, Vincent Wai-Sun Wong, George Boon Bee Goh
Received March 25, 2026  Accepted June 13, 2026  Published online June 18, 2026  
DOI: https://doi.org/10.3350/cmh.2026.0321    [Accepted]
Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease worldwide, associated with considerable clinical and economic burden. Early detection and timely intervention of Metabolic Dysfunction Associated Steatohepatitis (MASH) remains a key cornerstone of management. Traditionally, histopathology assessment is central to the characterization of MASH disease activity and fibrosis, albeit with inherent limitations. The advent of artificial intelligence (AI) has provided transformative tools to augment many aspects of MASH diagnostics, including histology assessment. New technologies enabling digitalization of pathology slides and allowing for further AI assisted model analysis have helped to address some of the previous limitations. In this review, we highlight the key AI assisted digital pathology tools, including utility, performance and clinical impact. Limitations and real-world considerations in adopting these AI tools are also explored.
  • 352 View
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Original Article

The natural history and individualized prediction of liver stiffness-based fibrosis risk in metabolic dysfunction-associated steatotic liver disease
Yu Shi, Ruoqi Zhou, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Manuel Romero-Gomez, Emmanuel Tsochatzis, Philip Newsome, Hannes Hagström, George Boon-Bee Goh, Wah-Kheong Chan, José-Luis Calleja, Jerome Boursier, Arun J. Sanyal, Jian-Gao Fan, Laurent Castera, Victor de Lédinghen, Michelle Lai, Xiao-Dong Zhou, Vincent Wai-Sun Wong, Ming-Hua Zheng, on behalf of VCTE-Prognosis Study Group
Clin Mol Hepatol 2026;32(3):1333-1348.
Published online May 20, 2026
DOI: https://doi.org/10.3350/cmh.2026.0279
Background/Aims
Liver stiffness measurement (LSM) is a key tool for risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD), yet static thresholds fail to capture dynamic transition across risk strata. We aimed to characterize LSM-risk transitions and develop a time-updated, individualized model for predicting state transitions, liver-related events and death (LREs/death).
Methods
In a real-world MASLD cohort, we applied a multi-state, time-homogeneous Markov model to quantify annual transition probabilities and mean state occupancy times across LSM-defined low-, intermediate-, and high-risk strata. A Markov model incorporating age, sex, type 2 diabetes (T2D), hypertension was used to generate individualized, time-updated risk trajectories and probabilities of LREs/death.
Results
Among 11,514 MASLD individuals with ≥2 vibration-controlled transient elastography assessments, the low-risk category demonstrated notable stability, with 92% remaining unchanged at 1 year and a mean occupancy time of 8.43 years (95% confidence interval [CI] 7.94–8.95). Contrarily, the intermediate-risk category was highly dynamic, with only 39% remaining unchanged after 1 year and a mean occupancy time of 0.92 years (95% CI 0.88–0.96). T2D, hypertension, and obesity substantially shorten low-risk occupancy time, whereas antidiabetic medication was associated with more favorable transitions. Finally, we developed a dynamic, multi-state Markov model integrating longitudinal LSM-defined risk states with relevant covariates to generate individualized predictions of state transitions and risks of LREs/death.
Conclusions
LSM-based strata in MASLD represent distinct and meaningful dynamic trajectories. In particular, the marked instability of the intermediate-risk state supports more frequent reassessment. By quantifying transition pathways and time-updated risks of LREs/death, this model may inform the personalized surveillance intervals and risk-adapted management.
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Correspondence

The lean phenotype in metabolic dysfunction-associated steatotic liver disease: diagnostic challenges and prognostic implications: Correspondence to editorial on “Normal-weight metabolic dysfunction-associated steatotic liver disease: reclassification, characteristics, and adverse liver outcomes across diverse populations”
Sherlot Ju Song, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Dae Won Jun
Clin Mol Hepatol 2026;32(3):e389-e391.
Published online February 5, 2026
DOI: https://doi.org/10.3350/cmh.2026.0143

Citations

Citations to this article as recorded by  Crossref logo
  • Rule-Out Cutoff of Two-Dimensional Shear Wave Elastography for Significant Fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease: Systematic Review, Meta-Analysis, and External Validation
    Joo Hyun Oh, Jonghyun Lee, Miyoung Choi, Kento Imajo, Masato Yoneda, Hideki Fujii, Hyo Young Lee, Eileen L. Yoon, Mimi Kim, Dae Won Jun
    Clinical Gastroenterology and Hepatology.2026;[Epub]     CrossRef
  • 1,023 View
  • 44 Download
  • Crossref

Reply to Correspondence

Reply to correspondence on “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis”
Yang-Hyun Baek
Clin Mol Hepatol 2026;32(3):e439-e440.
Published online January 27, 2026
DOI: https://doi.org/10.3350/cmh.2026.0068
  • 745 View
  • 23 Download

Editorials

A new lens on ferroptosis in liver disease: Near-infrared fluorescent probe of lipid peroxidation-driven microenvironmental remodeling: Editorial on “Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes”
Yunseo Bong, Wonhyo Seo
Clin Mol Hepatol 2026;32(3):1425-1428.
Published online January 27, 2026
DOI: https://doi.org/10.3350/cmh.2026.0003
  • 966 View
  • 45 Download
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
Clin Mol Hepatol 2026;32(3):1429-1432.
Published online January 9, 2026
DOI: https://doi.org/10.3350/cmh.2025.1482
  • 840 View
  • 53 Download
Bacteroides eggerthii: a new human gut probiotic against metabolic dysfunction-associated steatotic liver disease: Editorial on “Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host–microbe signaling and highlights 2-hydroxyisocaproate as a potential effector”
Harry Cheuk-Hay Lau, Jun Yu
Clin Mol Hepatol 2026;32(3):1400-1404.
Published online December 8, 2025
DOI: https://doi.org/10.3350/cmh.2025.1349
  • 696 View
  • 42 Download

Original Articles

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.
Results
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.

Citations

Citations to this article as recorded by  Crossref logo
  • Targeting ferroptosis to halt MASLD and MASH
    Fudi Wang
    Trends in Endocrinology & Metabolism.2026;[Epub]     CrossRef
  • 3,722 View
  • 272 Download
  • Crossref
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.
Results
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.

Citations

Citations to this article as recorded by  Crossref logo
  • Are FIB-4 and liver stiffness measurement interchangeable for HCC risk stratification in MASLD?
    Yimeng Zhou, Xue Meng
    JHEP Reports.2026; : 101852.     CrossRef
  • High Prevalence of Metabolic Dysfunction–Associated Steatohepatitis With Significant Fibrosis in Primary Care and Endocrinology Clinics
    Srilaxmi Kalavalapalli, Eddison Godinez Leiva, Andrea Ortiz Rocha, Anu Sharma, Diana Barb, Nathaly Cuervo‐Pardo, Kelly Y. Chun, Toni R. Prezant, Margery A. Connelly, Jens T. Rosenberg, Joseph R. Grajo, Fernando Bril, Kenneth Cusi
    Diabetes, Obesity and Metabolism.2026; 28(7): 6184.     CrossRef
  • The Evolution of MASLD Management: From Revised Nomenclature to Disease-Modifying Therapies
    Karolina Kornatowska, Szymon Kopciał, Mateusz Wiekiera, Adrianna Wiekiera, Paweł Budzik, Mateusz Tyniec, Kamal Morshed
    Gastroenterology Insights.2026; 17(2): 33.     CrossRef
  • 5,896 View
  • 419 Download
  • 2 Web of Science
  • Crossref
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.
Results
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.

Citations

Citations to this article as recorded by  Crossref logo
  • The MASLD Journey in the General Population: Linkage‐to‐Care and Patient‐Reported Uptake of Fibrosis Risk Assessment
    Joo Hyun Oh, Jun‐Hyuk Lee, Sang Bong Ahn, Eunjoo Kwon, Eileen L. Yoon, Hyo Young Lee, Seon Cho, Dae Won Jun
    Liver International.2026;[Epub]     CrossRef
  • 2,996 View
  • 154 Download
  • 1 Web of Science
  • Crossref
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.
Results
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.

Citations

Citations to this article as recorded by  Crossref logo
  • Letter to the Editor: Circadian and microbial misalignment in metabolic dysfunction-associated steatotic liver disease - mechanistic insights and chronotherapeutic potential
    Christos Savvidis, Ioannis Ilias
    World Journal of Experimental Medicine.2026;[Epub]     CrossRef
  • Decoding the Gut–Fat–Heart Axis: From Molecular Communication Networks to Clinical Translation Strategies
    Zijin Sun, Wei Shao, Haojia Zhang, Kai Wang, Yongchao Liu, Rui Zhou
    International Journal of Molecular Sciences.2026; 27(12): 5596.     CrossRef
  • 5,456 View
  • 456 Download
  • 2 Web of Science
  • Crossref

Correspondences

Correspondence to editorial 2 on “Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A”
Dongqin Yang, Yuli Lin, Chunhua Song, Ming Guan
Clin Mol Hepatol 2026;32(3):e342-e345.
Published online September 29, 2025
DOI: https://doi.org/10.3350/cmh.2025.1100
  • 1,312 View
  • 71 Download
Correspondence to editorial 1 on “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, Dongqin Yang, Zhihao Wu, Ming Guan, Chunhua Song
Clin Mol Hepatol 2026;32(3):e339-e341.
Published online September 29, 2025
DOI: https://doi.org/10.3350/cmh.2025.1086
  • 1,074 View
  • 41 Download

Editorials

ASB3 degrades the gateway to β-oxidation: Editorial on “Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A”
Ho Jae Ryu, Ji Su Han, Ja Hyun Koo
Clin Mol Hepatol 2026;32(3):1379-1382.
Published online September 23, 2025
DOI: https://doi.org/10.3350/cmh.2025.1021

Citations

Citations to this article as recorded by  Crossref logo
  • TREM1-mediated macrophage activation drives voriconazole-induced hepatic steatosis: Diagnostic and therapeutic implications
    Jing Liu, Mingxia Deng, Xiaoying He, Jing Ma, Li Zhang, Xi Yang, Jinyao Dai, Shaohua Dong, Yichun Zhang, Zhijuan Zhang, Shuaibing Ying, Haoyang Hu, Lushun Jiang, Yujing Wang, Yunqing Qiu, Yan Lou
    Journal of Pharmaceutical Analysis.2026; 16(6): 101540.     CrossRef
  • 1,547 View
  • 146 Download
  • Crossref
Targeting the ASB3-CPT1A axis—a new player in combating metabolic dysfunction-associated steatotic liver disease: Editorial on “Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyltransferase 1A”
Yueying Yang, Ying Yang, Yan Lu
Clin Mol Hepatol 2026;32(2):957-959.
Published online September 15, 2025
DOI: https://doi.org/10.3350/cmh.2025.1013
  • 1,994 View
  • 86 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.

Citations

Citations to this article as recorded by  Crossref logo
  • Obesity, Metabolic Syndrome and MASLD in Children: Inflammation as the Missing Link—A Short Narrative Review
    Mihaela-Andreea Podeanu, Claudiu Marinel Ionele, Raluca Elena Sandu, Ion Rogoveanu, Mioara Desdemona Stepan, Carmen Elena Niculescu, Sergiu-Marian Cazacu, Ștefănița Bianca Vintilescu
    Life.2026; 16(2): 310.     CrossRef
  • Artificial intelligence for metabolic dysfunction-associated steatotic liver disease diagnosis: A systematic review
    Ruijuan Wang, Chang Liu, Mei Xue, Jun Qian, Yue Hu
    Computers in Biology and Medicine.2026; 208: 111619.     CrossRef
  • Effects of metabolic syndrome on pulmonary infection in pediatric bronchial asthma: a narrative review
    Li He, Yang Ye
    Frontiers in Pediatrics.2026;[Epub]     CrossRef
  • Microbial metabolites at the nexus of gut-brain communication and neurodevelopmental disorders
    Yupeng Lai, Ming Zhang, Dandan Lang, Enfu Tao
    Frontiers in Nutrition.2026;[Epub]     CrossRef
  • Targeting the Human Gut Microbiota—Between Conventional Therapy and Precision Genetic Engineering
    Naomi-Adina Ciurea, Laura Mahdi, Annarita Graziani, Agostino Di Ciaula, Piero Portincasa, Mohamad Khalil
    Nutrients.2026; 18(12): 1958.     CrossRef
  • 9,066 View
  • 326 Download
  • 3 Web of Science
  • Crossref

Letters to the Editor

Letter to the editor on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
Chunyan Wang, Xu Han, Yinyan Li
Clin Mol Hepatol 2026;32(2):e167-e169.
Published online August 19, 2025
DOI: https://doi.org/10.3350/cmh.2025.0676
  • 2,829 View
  • 55 Download
Letter to the editor 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
Clin Mol Hepatol 2026;32(2):e139-e140.
Published online August 8, 2025
DOI: https://doi.org/10.3350/cmh.2025.0875
  • 3,483 View
  • 33 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.
Results
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.

Citations

Citations to this article as recorded by  Crossref logo
  • Targeting the ASB3-CPT1A axis—a new player in combating metabolic dysfunction-associated steatotic liver disease: Editorial on “Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver diseas
    Yueying Yang, Ying Yang, Yan Lu
    Clinical and Molecular Hepatology.2026; 32(2): 957.     CrossRef
  • The first genome-wide association study on pediatric obesity in Taiwan
    Hsin-Ru Wu, Ting-Yuan Liu, Chuan-Mu Chen, Fuu-Jen Tsai
    Journal of the Formosan Medical Association.2026;[Epub]     CrossRef
  • 6,800 View
  • 538 Download
  • 1 Web of Science
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Editorials

The other face of GWAS: Editorial on “Genome-wide interaction study with body mass index identifies CYP7A1 and GIPR as genetic modulators of metabolic dysfunction-associated steatotic liver disease”
Hyungtai Sim, Murim Choi
Clin Mol Hepatol 2026;32(2):928-930.
Published online July 8, 2025
DOI: https://doi.org/10.3350/cmh.2025.0677
  • 2,469 View
  • 46 Download
Rethinking first-line screening in MASLD beyond the limitations of Fibrosis-4 index: Editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
Han Ah Lee, Young Youn Cho, Hyung Joon Kim
Clin Mol Hepatol 2026;32(2):921-923.
Published online June 27, 2025
DOI: https://doi.org/10.3350/cmh.2025.0678
  • 3,840 View
  • 61 Download

Letter to the Editor

Letter to the editor on “Genome-wide interaction study with BMI identifies CYP7A1 and GIPR as genetic modulators of MASLD”
Sheng Zheng
Clin Mol Hepatol 2026;32(2):e170-e171.
Published online June 27, 2025
DOI: https://doi.org/10.3350/cmh.2025.0656
  • 2,182 View
  • 35 Download

Correspondence

Correspondence to letter to the editor on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
Hye Won Lee, Seung Up Kim
Clin Mol Hepatol 2026;32(2):e244-e245.
Published online June 24, 2025
DOI: https://doi.org/10.3350/cmh.2025.0644
  • 3,927 View
  • 24 Download

Editorial

GLP-1RA may open a new era for MASLD treatment: Editorial on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
Ye Feng, Chengfu Xu
Clin Mol Hepatol 2026;32(2):924-927.
Published online June 24, 2025
DOI: https://doi.org/10.3350/cmh.2025.0628

Citations

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  • Correspondence to editorial on “Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study”
    Xianhua Mao, Mindie H. Nguyen
    Clinical and Molecular Hepatology.2026; 32(2): e219.     CrossRef
  • 3,338 View
  • 120 Download
  • Crossref

Letter to the Editor

Letter to the editor on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
Chunyan Wang, Jun Sun, Yinyan Li
Clin Mol Hepatol 2026;32(2):e146-e148.
Published online June 9, 2025
DOI: https://doi.org/10.3350/cmh.2025.0539

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to letter to the editor 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(2): e244.     CrossRef
  • 3,983 View
  • 45 Download
  • 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

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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
  • 6,347 View
  • 50 Download
  • Crossref

Original Article

Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study
Xianhua Mao, Xinrong Zhang, Rongtao Lai, Ka-Shing Cheung, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen
Clin Mol Hepatol 2025;31(3):1084-1099.
Published online April 23, 2025
DOI: https://doi.org/10.3350/cmh.2024.1096
Background/Aims
Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.
Methods
Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).
Results
In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77.
Conclusions
In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.

Citations

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  • How Negative Controls Are Used in Pharmacoepidemiology: A Methodological Scoping Review of Real‐World Observational Studies of Glucagon‐Like Peptide‐1 Receptor Agonists
    Zhengxuan Li, Yinan Huang, Hua Chen, Jieni Li
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  • Cancer outcomes and biological mechanisms among patients with type 2 diabetes mellitus using glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis
    Ejike Daniel Eze, Leopold Ntakirutimana, Swase Dominic Terkimbi, Muluken Walle, Abdullahi Hussein Umar, Diresibachew Haile Wondimu, Makinde Vincent Olubiyi, Onyinye Cynthia Okeke, Olufunke Onaadepo, Jimoh Abdulazeez, David Chibuike Ikwuka, Elemi John Ani,
    Frontiers in Oncology.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
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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

Citations to this article as recorded by  Crossref logo
  • 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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    Shang-Chin Huang, Jia-Horng Kao
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    Shang-Chin Huang, Tai-Chung Tseng
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    Dong Hyun Sinn, Kyung-Ah Kim, Jung Il Lee, Geum-Youn Gwak
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Original Articles

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.
Results
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.

Citations

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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
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    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
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    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
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    Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Andrew F. Ibrahim, Primrose Tothanarungroj, Omar Al Ta'ani, Narathorn Kulthamrongsri, Kwanjit Duangsonk, Robert J. Wong, Daniel Q. Huang, Karn Wijarnpreecha, Mazen Noureddin, Suthat Liangpunsakul
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    Pojsakorn Danpanichkul, Francisco Idalsoaga, Frank Murray, Juan Pablo Arab, Luis Antonio Díaz
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    Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Mark D. Muthiah, Suthat Liangpunsakul
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    Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
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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.
Results
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.

Citations

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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
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    Hye Won Lee, Seung Up Kim
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    Beom Kyung Kim
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    Dong Yun Kim, Hyung-Jin Rhee, Beom Kyung Kim
    Clinical and Translational Gastroenterology.2026;[Epub]     CrossRef
  • Validation of combo ichroma as a reliable concentration-based alternative for AST and ALT measurement in liver disease monitoring
    Minsoo Kim, Su A Kim, Jeong Min Kim, Hee Young Kim, Ho Yeong Yoon, Sung Won Park, Daegyun Park, Ji Sook Han, Ki Tae Suk
    Methods.2025; 243: 66.     CrossRef
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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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    Jenyfer M Fuentes-Mendoza, Marcio J Concepción-Zavaleta, Jeny J Mendoza-Godoy, Luis A Concepción-Urteaga, Carlos O Martínez-Gutiérrez, José Paz-Ibarra
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    Beom Kyung Kim
    The Kaohsiung Journal of Medical Sciences.2026;[Epub]     CrossRef
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    Koral S. E. Richard, Sumati Rohilla, Reethika Gade, Fabio Arias, Oren Rom
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    Ling-Feng Zhang, Su-Qing Liang, Qing-Wen Huang, Jia-Wen Ru, Ze-Quan Ding, Chun-Yu Zhang, Yi Wang, Tian-Jiao Zhou, Lei Xing, Xian Wu Cheng, Yu-Kyoung Oh, Hu-Lin Jiang
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    Karolina Kornatowska, Szymon Kopciał, Mateusz Wiekiera, Adrianna Wiekiera, Paweł Budzik, Mateusz Tyniec, Kamal Morshed
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    Ziyan Pan, Abdulla Al Hassani, Khalid M. AlNaamani, Yasser Fouad, Munira Y. Altarrah, Mohammed Eslam
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    Dong Yun Kim, Hyung-Jin Rhee, Beom Kyung Kim
    Clinical and Translational Gastroenterology.2026;[Epub]     CrossRef
  • Insights into Metabolic-Inflammatory Dual-targeting Effects of Huangqi Guizhi Wuwu Decoction on Diabetic Hepatopathy via Regulation of the AMPK-FASN/PI3K-AKT Axis
    Sheng-Wen Lu, Qi-Qi Zhao, Zhi-Bo Wang, Si-Fan Guo, Ying Cai, Xian Wang, Dan-Dan Xie, Zhen-Cai Hu, Shi-Wei Wang, Ai-Hua Zhang, Yu Guan, Shi Qiu
    World Journal of Traditional Chinese Medicine.2026;[Epub]     CrossRef
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    Caichen Zhong, Nana Boame, Semiu O. Gbadamosi, Maximilian Jara, Rakesh Luthra, Alex Salamun, Yu Hong, Abdalla Aly, Fernando Bril, Mary E. Rinella
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    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
    Nutrients.2025; 17(13): 2189.     CrossRef
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    Amedeo Lonardo, Ralf Weiskirchen
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    Ziyi Lin, Peng Xu, Yuehai Xu, Yixin Zheng, Huimin Li, Zixin Chen, Zhe Wang, Shaochen Song, Yuhao Liu, Zhao Yang, Ju Cui, Heyun Shen
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Letters to the Editor

Letter to the editor on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”
Sisi Yang, Zhenxuan Ma
Clin Mol Hepatol 2026;32(1):e4-e6.
Published online March 7, 2025
DOI: https://doi.org/10.3350/cmh.2025.0153
  • 5,668 View
  • 52 Download
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
  • 9,432 View
  • 82 Download

Special Issue

Steatotic liver disease

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

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    Sikyeong Park, Yu Shin Park, Dahye Hong, Bada Kang
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  • Risk Stratification of Chronic Kidney Disease in Adults Using Noninvasive Fibrosis Tests Based on the American Diabetes Association Algorithm
    Chan‐Young Jung, Hye Won Lee, Jung Il Lee, Han Ah Lee, Seung Up Kim
    Diabetes, Obesity and Metabolism.2026; 28(6): 5240.     CrossRef
  • Rethinking first-line screening in MASLD beyond the limitations of Fibrosis-4 index: Editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
    Han Ah Lee, Young Youn Cho, Hyung Joon Kim
    Clinical and Molecular Hepatology.2026; 32(2): 921.     CrossRef
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    Beom Kyung Kim
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    Jian Xu, Wei Zhang, Guo Wu, Jingdong Li
    Clinical and Molecular Hepatology.2026; 32(2): e257.     CrossRef
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    Soo Lim, Hui Zhou, Wataru Ogawa
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    Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
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  • Implication of the Androgen Receptor in Muscle–Liver Crosstalk: An Overlooked Mechanistic Link in Lean-MASLD
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  • Crossref

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
  • 6,727 View
  • 55 Download

Reply to Correspondence

Steatotic liver disease

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
Clin Mol Hepatol 2025;31(2):e218-e220.
Published online February 3, 2025
DOI: https://doi.org/10.3350/cmh.2025.0070
  • 6,439 View
  • 33 Download

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

Citations

Citations to this article as recorded by  Crossref logo
  • Comparison of the identification and practicability of non-invasive diagnostic indicators under NAFLD, MAFLD and MASLD in China: a cross-sectional study
    Xin-Yun Tan, Hui-Hui Zou, Xinjuan Huang, Man-Jie Guo, Ruo-Ling Yu, Xue-Lian Liu, Ting Peng, Xuan Yang, Chun-Xiang Qin
    BMJ Open.2026; 16(4): e094809.     CrossRef
  • 12,604 View
  • 105 Download
  • 1 Web of Science
  • Crossref

Correspondences

Steatotic liver disease

Correspondence to letter to the editor 2 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):e210-e211.
Published online January 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.1175
  • 7,423 View
  • 39 Download

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
  • 7,500 View
  • 45 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
  • 8,678 View
  • 63 Download
  • 1 Web of Science
  • Crossref

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

Citations to this article as recorded by  Crossref logo
  • 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
  • 8,173 View
  • 54 Download
  • 2 Web of Science
  • Crossref

Letter to the Editor

Hepatic neoplasm

Letter to the editor on “Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study”
Hai Xu, Yong Zhou, Huikun Wu
Clin Mol Hepatol 2025;31(2):e125-e127.
Published online December 17, 2024
DOI: https://doi.org/10.3350/cmh.2024.1087

Citations

Citations to this article as recorded by  Crossref logo
  • 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
    Clinical and Molecular Hepatology.2025; 31(2): e208.     CrossRef
  • 8,117 View
  • 45 Download
  • 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.

Citations

Citations to this article as recorded by  Crossref logo
  • 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.2026; 18(3): 4353.     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
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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.
Results
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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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

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Letter to the Editor

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

Citations

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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.

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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

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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

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