Clinical and Molecular Hepatology

Alcohol-Aware Risk Stratification and Subtype-Specific Care Pathways Across MASLD, MetALD, and ALD: Hyo Young Lee, Eileen Laurel Yoon, Dae Won Jun; Received May 27, 2026 Accepted August 10, 2026 Published online August 14, 2026; DOI: https://doi.org/10.3350/cmh.2026.0659 [Accepted]

Abstract
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Accurate classification and risk stratification across metabolic dysfunction-associated steatotic liver disease (MASLD), MetALD, and alcohol-associated liver disease (ALD) depend critically on the assessment of alcohol exposure. However, current clinical practice relies largely on self-reported alcohol intake, which may underestimate drinking quantity, pattern, and prior heavy exposure and consequently lead to subtype misclassification. This review focuses on an alcohol-aware approach to steatotic liver disease (SLD) phenotyping and clinical management. We discuss the complementary role of structured alcohol assessment and objective biomarkers, particularly phosphatidylethanol (PEth), while emphasizing biological, analytical, and host factors that limit interpretation of a single biomarker value. We further examine how active or recent alcohol exposure modifies the interpretation of commonly used risk-stratification tools, particularly FIB-4 and liver stiffness measurement, and when repeat assessment after alcohol reduction or abstinence may be appropriate. Finally, we propose practical subtype-specific care pathways integrating alcohol exposure, non-invasive fibrosis assessment, and longitudinal reassessment across MASLD, MetALD, and ALD. An alcohol-aware approach may reduce subtype misclassification and enable more appropriate referral, monitoring, and therapeutic decision-making across the SLD spectrum.

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Dynamic Transitions in Steatotic Liver Disease Subtypes and Risk of Liver-Related Events: A Nationwide Cohort Study: Yewan Park, Jooyi Jung, Seungbong Han, Hyeyeon Hong, Gi-Ae Kim; Received April 1, 2026 Accepted July 15, 2026 Published online July 30, 2026; DOI: https://doi.org/10.3350/cmh.2026.0408 [Accepted]

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Introduction
Although steatotic liver disease (SLD) is a dynamic condition, the prognostic impact of subtype transitions over time remains unclear. We investigated the association between SLD subtype transitions and the risk of long-term liver-related events (LREs).
Methods
From the Korean National Health Insurance Service database, adults who underwent national health checkups in both 2015 and 2017 were recruited. SLD subtypes included metabolic dysfunction–associated SLD, metabolic and alcohol-related SLD, and alcohol-related liver disease. Transitions were classified into no transitions, transitions to more advanced subtypes, and transitions to less advanced subtypes. LREs included incident cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related mortality. Subdistribution hazard ratios (sHRs) were estimated using Fine–Gray competing-risk models.
Results
Among 1,988,878 individuals, 21.7% transitioned over two years: 11.3% transitioned to more advanced subtypes, whereas 10.4% transitioned to less advanced subtypes. In each SLD subtype, transitions to more advanced subtypes showed a higher risk of LREs, whereas transitions to less advanced subtypes showed a lower risk of LREs. In SLD, the transitions to more advanced subtypes showed a higher risk of LREs (sHR, 1.34; 95% confidence interval [CI], 1.28–1.40), whereas transitions to less advanced subtypes showed a lower risk (sHR, 0.86; 95% CI, 0.83–0.88). Sensitivity analyses stratified by sex, BMI, and a fatty liver index threshold of >60 demonstrated comparable findings.
Conclusion
We found that transitions to more advanced SLD subtypes showed increased risks of LREs, whereas transitions to less advanced subtypes showed risk reduction. The findings highlight the need for management schemes considering SLD subtype changes over time.

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Oral anticoagulants and hepatic decompensation in patients with cirrhosis and atrial fibrillation: observational study: Axel Wester, Emilie Toresson Grip, Rupesh Rajani, Anthony A. Matthews, Hannes Hagström, Ying Shang; Received March 5, 2026 Accepted July 11, 2026 Published online July 15, 2026; DOI: https://doi.org/10.3350/cmh.2026.0286 [Accepted]

Abstract
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Background/Aims
Oral anticoagulants may reduce risk of hepatic decompensation in patients with compensated cirrhosis, but well-powered randomized trials are missing. We aimed to estimate the effect of oral anticoagulants on risk of hepatic decompensation and major bleeding in patients with compensated cirrhosis and atrial fibrillation.
Methods
Observational data from Swedish healthcare registers 2011-2022 were used to emulate a target trial of oral anticoagulants in patients with compensated cirrhosis and newly diagnosed atrial fibrillation. Inverse-probability weighted marginal structural models were used to compare 5-year risks of hepatic decompensation and non-portal hypertension-related major bleeding in initiators versus non-initiators of oral anticoagulants.
Results
The study included 1,160 patients (715 men [61.6%]; median [p25-p75] age of 73 years [67-79]). The 5-year risk of hepatic decompensation was 10.4% (33/383) in initiators and 16.6% (112/777) in non-initiators (risk ratio [RR]=0.62, 95% confidence interval [CI]=0.33-0.92), corresponding to a number needed to treat of 17 (95%CI=9-112). The risk reduction was primarily driven by a reduced risk of ascites (RR=0.58, 95%CI=0.26-0.90). The risk of major bleeding was 19.0% (63/383) in initiators and 19.8% (149/777) in non-initiators (RR=0.96, 95%CI=0.64-1.28). Risks were similar between treatment groups regarding fatal, intracranial, gastrointestinal, and other bleedings.
Conclusions
In this nationwide observational study, patients with compensated cirrhosis and atrial fibrillation who initiated oral anticoagulants had lower risk of hepatic decompensation, and similar risk of major bleeding compared to non-initiators. The results suggest oral anticoagulants are safe in patients with compensated cirrhosis and may improve prognosis. Randomized trials are warranted to confirm these results.

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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]

Abstract
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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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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]

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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.

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Ursodeoxycholic acid and long COVID in steatotic liver disease: a nationwide cohort study: Kyungyeon Jung, Gi-Ae Kim, Jieun Woo, Jin Youn, Eun-Young Choi, Sungho Bea, Ahhyung Choi, Ju Hwan Kim, Heejoon Jang, Dong Hyeon Lee, Sae Kyung Joo, Ju-Young Shin, Won Kim; Clin Mol Hepatol 2026;32(3):1364-1378.
Published online June 9, 2026; DOI: https://doi.org/10.3350/cmh.2026.0283

Background/Aims
Ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme 2, the cellular entry receptor for SARS-CoV-2, and may reduce acute coronavirus disease 2019 (COVID-19) severity. However, it remains unknown whether UDCA prevents long COVID outcomes in patients with steatotic liver disease (SLD)—a population vulnerable to adverse outcomes. We investigated the association between pre-infection UDCA use and risk of long COVID outcomes in patients with SLD.
Methods
We conducted a nationwide retrospective cohort study using the Korean COVID-19 registry linked to National Health Insurance Service claims data (2019–2022). Patients with SLD (fatty liver index ≥30) who experienced COVID-19 were included. Exposure was defined as at least one UDCA prescription within the 90 days preceding infection. Outcomes of interest were 20 incident long COVID conditions across eight organ systems assessed ≥84 days post-infection. After propensity score (PS) fine stratification, hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression.
Results
Among 469,108 patients with SLD and COVID-19, 23,560 (5.0%) were UDCA users. After PS fine stratification weighting, UDCA use was not associated with reduced risk for most long COVID outcomes. A protective association was observed for atrial fibrillation (HR 0.51, 95% CI 0.30–0.88), whereas increased risks were found for type 2 diabetes mellitus (HR 1.24, 95% CI 1.09–1.42) and epilepsy (HR 1.69, 95% CI 1.09–2.61).
Conclusions
Pre-infection UDCA use was not associated with reduced risk for most long COVID outcomes in patients with SLD. The observed associations warrant cautious interpretation given potential residual confounding and surveillance bias.

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Hepatic fibro-inflammation measured by magnetic resonance imaging iron-corrected T1 predicts extrahepatic cancer risk: a UK Biobank study: Hye Yeon Chon, Seok-Jae Heo, SungA Bae, Tae Seop Lim, Ja Kyung Kim; Clin Mol Hepatol 2026;32(3):1349-1363.
Published online June 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1372

Background/Aims
Iron-corrected T1 (cT1) is a magnetic resonance imaging (MRI)-derived biomarker of hepatic fibro-inflammation. This study aimed to investigate whether high cT1 values are associated with an increased risk of extrahepatic malignancy in a large prospective cohort.
Methods
We included 24,003 cancer-free participants from the United Kingdom (UK) Biobank with liver MRI and complete covariate data. Incident extrahepatic malignancy was assessed over a median follow-up of 4.28 years. Multivariable Fine–Gray subdistribution hazard models were used to evaluate the association between cT1 and extrahepatic cancer risk, accounting for competing risks and adjusting for demographic, metabolic, and liver-related factors.
Results
During follow-up, 1,144 participants developed extrahepatic malignancies. In the multivariable analysis, higher cT1 was independently associated with increased extrahepatic cancer risk (hazard ratio [HR] 1.116; 95% confidence interval [CI] 1.033–1.205; per standard deviation increase; P=0.005). Older age (HR 1.512; 95% CI 1.402–1.631) and male sex (HR 1.388; 95% CI 1.220–1.578) were also significant predictors (P<0.001). The fibrosis-4 score showed a modest positive association (HR 1.032; 95% CI 1.004–1.062; P=0.026), whereas MRI-proton density fat fraction demonstrated an inverse association (HR 0.906; 95% CI 0.832–0.987; P=0.024). When dichotomized at 771 ms, elevated cT1 was associated with a higher cumulative incidence of extrahepatic malignancy (6.1% vs. 4.6%, P=0.002).
Conclusions
Elevated cT1 is independently associated with an increased risk of future extrahepatic malignancy, suggesting that it may reflect systemic disease processes related to cancer risk. These findings highlight the potential relevance of cT1 beyond liver-specific outcomes; however, further validation is required before clinical implementation.

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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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Burden of cardiovascular complications in steatotic liver disease in the United States: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed; Clin Mol Hepatol 2026;32(3):e326-e330.
Published online March 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0249

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Extrahepatic mortality associated with chronic liver disease with or without cirrhosis from 2014 to 2024: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed; Clin Mol Hepatol 2026;32(2):e194-e198.
Published online February 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0225

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Navigating discordant non-invasive fibrosis assessments in metabolic dysfunction-associated steatotic liver disease: Implications for generalizability, clinical decision-making, and resource allocation: Letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”: Jiajing Zhao, Liping Liu; Clin Mol Hepatol 2026;32(3):e300-e302.
Published online February 20, 2026; DOI: https://doi.org/10.3350/cmh.2025.0157

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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 Juan 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

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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

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Critical considerations on the study of normal-weight metabolic dysfunction-associated steatotic liver disease across diverse populations: Letter to the Editor on “Normal-weight metabolic dysfunction-associated steatotic liver disease: Reclassification, characteristics, and adverse liver outcomes across diverse populations”: Qingshang Li, Xiaona Hu, Yuanwen Chen, Zhijun Bao; Clin Mol Hepatol 2026;32(3):e309-e311.
Published online February 5, 2026; DOI: https://doi.org/10.3350/cmh.2026.0067

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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

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Rethinking lean metabolic dysfunction-associated steatotic liver disease: Unrecognized risk in lean populations: Editorial on “Normal-weight metabolic dysfunction-associated steatotic liver disease: Reclassification, characteristics, and adverse liver outcomes across diverse populations”: Donghee Kim, Anoushka Shenoy, Aijaz Ahmed; Clin Mol Hepatol 2026;32(3):1441-1443.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0056

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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, ch
Sherlot Juan Song, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(3): e389. CrossRef

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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

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Reply to correspondence on “Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes”
Yunseo Bong, Wonhyo Seo
Clinical and Molecular Hepatology.2026; 32(3): e437. CrossRef
Correspondence to editorial on “Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes”
Taeeung Kim, Le Bich Hang Pham, Jeeyeon Lee, Keon Wook Kang
Clinical and Molecular Hepatology.2026; 32(3): e375. CrossRef

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DNMT1 facilitates the progression of metabolic dysfunction-associated steatotic liver disease by impeding transcription mediated by HNF4α and PPARα: Hyun Ahm Sohn, Hanyong Go, Tae Hyeon An, Jun Min Lee, Hee-Jin Kim, Keeok Haam, Amal Magdy, Hyo-Jung Jung, Yang-Ji Shin, Hyun Jung Lim, Yujin Jeong, Yejin Bae, Youngae Jung, Seong-Hwan Park, Kyung Chan Park, Myeong Jun Song, Eun-Wie Cho, Eun-Soo Kwon, Jeong Hwan Park, Murim Choi, Geum-Sook Hwang, Dong Hyeon Lee, Kyoung-Jin Oh, Won Kim, Mirang Kim, on behalf of the Innovative Target Exploration of NAFLD (ITEN) Consortium; Clin Mol Hepatol 2026;32(3):1201-1224.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2025.1099

Background/Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Aberrant DNA methylation, which is primarily maintained by DNA methyltransferase 1 (DNMT1), has been linked to metabolic dysregulation; however, its contribution to MASLD pathogenesis remains poorly defined. This study aimed to elucidate the role of DNMT1-mediated methylation in transcriptional regulation during MASLD progression and to determine whether DNMT1 inhibition can reverse disease-associated epigenetic and transcriptional alterations.
Methods
We conducted integrated analyses of the liver transcriptome (n=131) and DNA methylome (n=106) of patients with biopsy-proven MASLD. We evaluated the effect of DNMT1 inhibition with 5-aza-4′-thio-2′-deoxycytidine (Aza-TdC) on a diet-induced MASLD mouse model. Multiomics approaches, including DNA methylome profiling, lipidomics, RNA sequencing, and chromatin immunoprecipitation sequencing, were applied to elucidate the role of DNMT1-mediated DNA methylation in regulating pathogenic gene expression.
Results
DNA methylome profiling revealed increased methylation variability associated with increased DNMT1 expression in MASLD patients. DNMT1 inhibition ameliorated dysregulated lipid metabolism by reducing hepatic triacylglycerol accumulation and inflammation. Aza-TdC treatment partially reversed MASLD-related hypermethylation of hepatocyte nuclear factor 4 alpha (HNF4α)- and peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes, restoring their transcriptional activity. Notably, Aza-TdC reactivated the gluconeogenic enzyme-encoding gene phosphoenolpyruvate carboxykinase 1 (PCK1), which was hypermethylated and transcriptionally repressed in MASLD. Targeted DNA methylation of the PCK1 promoter using CRISPRoff confirmed the direct epigenetic regulation of PCK1 expression.
Conclusions
Targeting DNMT1 may mitigate lipid dysregulation and inflammation by reversing hypermethylation and restoring HNF4α- and PPARα-dependent gene transcription, highlighting DNMT1 as a potential therapeutic target for MASLD.

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Sus scrofa domesticus reveals the genetic evolution of adaptive traits during early divergence
Bohan Rong, Naiqi Niu, Wencheng Zong, Run Zhang, Xiaomei Ma, Na Zhang, Zhentong Shen, Yu Pang, Xu Lin, Di Liu, Yulong Yin, Longchao Zhang, Xiuqin Yang
The Innovation Life.2026; : 100222. CrossRef
Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks
Zijin Sun, Yongchao Liu, Kai Wang, Haojia Zhang, Rui Zhou, Wei Shao
International Journal of Molecular Sciences.2026; 27(12): 5526. CrossRef
From linear methylation to spatial metabolic control: Rethinking DNMT1 targeting in MASLD: Letter to the editor on “DNMT1 facilitates the progression of MASLD by impeding transcription mediated by HNF4α and PPARα”
Yao Liu, Qitai Song, Muhu Chen
Clinical and Molecular Hepatology.2026; 32(3): e317. CrossRef

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Clinical implications of discordant FIB-4 and LSM in MASLD: Integrating evidence and optimizing pathways: Letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”: Deliang Huang, Jun Chen; Clin Mol Hepatol 2026;32(3):e294-e296.
Published online January 20, 2026; DOI: https://doi.org/10.3350/cmh.2026.0027

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Correspondence to letter to the editor on “Histological severity and hepatic outcomes in patients with metabolic dysfunction-associated steatotic liver disease and discrepant FIB-4 and liver stiffness measurement”
Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Seung Up Kim
Clinical and Molecular Hepatology.2026; 32(3): e419. CrossRef

1,165 View
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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; Clin Mol Hepatol 2026;32(3):1429-1432.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1482

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Correspondence to editorial 1 on “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis”
Moon Haeng Hur, Hyunjae Shin, Yoon Jun Kim
Clinical and Molecular Hepatology.2026; 32(3): e378. CrossRef
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
Clinical and Molecular Hepatology.2026; 32(3): e439. CrossRef

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Reply to correspondence on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”: Seol Hee Park, Wonhyo Seo; Clin Mol Hepatol 2026;32(3):e432-e433.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1469

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Microbial Biomarkers for the Prevention and Diagnosis of Alcoholic Liver Disease
Goo Hyun Kwon, Hyunjoon Park, Hyeong Seop Kim, Ki Kwang Oh, Jung A Eom, Kyeong Jin Lee, Min Ju Kim, Minsoo Kim, Jeong Su Kim, Sang Hak Han, Young Lim Ham, Ki Tae Suk
Microorganisms.2026; 14(2): 449. CrossRef

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RAB25 as a liver-selective modulator of endoplasmic reticulum stress in alcohol-associated liver disease: Correspondence to editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”: Zi-Bin Zhan, Xue-Wen Liu, Ze-Hua Li, Fan-Hong Zeng, Kun-Hao Bai, Jun Weng; Clin Mol Hepatol 2026;32(3):e354-e357.
Published online January 6, 2026; DOI: https://doi.org/10.3350/cmh.2025.1422

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

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

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

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Correspondence to editorial on “Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host-microbe signaling and highlights 2-hydroxyisocaproate as a potential effector”: Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun; Clin Mol Hepatol 2026;32(3):e361-e364.
Published online December 23, 2025; DOI: https://doi.org/10.3350/cmh.2025.1416

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1,042 View
37 Download

Correspondence to editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”: Xue-Wen Liu, Zi-Bin Zhan, Yu Gong, Ze-Hua Li, Kun-Hao Bai, Jun Weng; Clin Mol Hepatol 2026;32(3):e349-e353.
Published online December 23, 2025; DOI: https://doi.org/10.3350/cmh.2025.1397

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Reply to correspondence on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”
Seol Hee Park, Wonhyo Seo
Clinical and Molecular Hepatology.2026; 32(3): e432. CrossRef

1,277 View
56 Download
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Correspondence to editorial on “Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production”: Dianji Tu, Cheng Lu, Bo Tang, Shiming Yang; Clin Mol Hepatol 2026;32(3):e358-e360.
Published online December 23, 2025; DOI: https://doi.org/10.3350/cmh.2025.1385

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Burden of malnutrition and sarcopenia in patients with cirrhosis: pathophysiology, assessment, and management: Takao Miwa, Masahito Shimizu, Bernd Schnabl; Clin Mol Hepatol 2026;32(2):487-510.
Published online December 16, 2025; DOI: https://doi.org/10.3350/cmh.2025.1126

Abstract
PDF

Malnutrition and sarcopenia are highly prevalent and robustly associated with reduced quality of life, disease progression, and poor outcomes, including complications and mortality, in patients with cirrhosis. Their pathophysiology is multifactorial, involving inadequate dietary intake and malabsorption, impaired liver functional reserves, altered energy, protein, and ammonia metabolism, systemic inflammation, hormonal dysregulation, and lifestyle or environmental influences. Despite extensive research, unresolved issues remain regarding optimal diagnostic criteria, as current approaches vary and lack global standardization. Regarding the diagnostic criteria for malnutrition, the usefulness of the Global Leadership Initiative on Malnutrition criteria has been proposed by international nutrition societies. However, evidence supporting their applicability in hepatology remains insufficient. For sarcopenia, differences in disease concept and diagnostic methods among societies indicate that no unified diagnostic standard exists, and clinicians should approach diagnosis with an understanding of the strengths and limitations of each method. Nutritional strategies emphasize adequate energy and protein intake, late evening snacks, and branched-chain amino acid supplementation, while deficiencies in micronutrients require tailored replacement. Nutritional therapy alone has limited effect on sarcopenia, but when combined with exercise it improves muscle mass, physical performance, and outcomes. Comprehensive approaches integrating optimized nutrition, micronutrient support, and structured exercise are essential to alleviate the burden of malnutrition and sarcopenia and to improve prognosis in patients with cirrhosis. This review addresses malnutrition and sarcopenia in cirrhosis by highlighting their prevalence, pathophysiology, clinical impact, and approaches for screening and diagnosis, and by emphasizing personalized nutritional, pharmacological, and exercise interventions to improve patient outcomes.

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Letter: Amino Acid Imbalance Is an Independent Factor for Mortality in Patients With Liver Cirrhosis. Authors' reply
Yuki Utakata, Takao Miwa, Shinji Unome, Naoya Masuda, Mikita Oi, Masashi Aiba, Kenji Imai, Koji Takai, Makoto Shiraki, Naoki Katsumura, Masahito Shimizu
Alimentary Pharmacology & Therapeutics.2026; 63(9): 1329. CrossRef
Covert hepatic encephalopathy as a multi-organ syndrome: the gut–liver–muscle–brain axis, diagnosis, treatment, and multidisciplinary care
Takao Miwa, Cynthia L. Hsu, Masahito Shimizu, Patricia P. Bloom, Bernd Schnabl
Journal of Gastroenterology.2026; 61(9): 1217. CrossRef
Nutrition in cirrhosis: bridging guidelines and practice in hepatic disease
Jennifer Jin, Puneeta Tandon, Leah Gramlich
Current Opinion in Clinical Nutrition & Metabolic Care.2026; 29(5): 494. CrossRef
Letter: Major Adverse Outcomes in Steatotic Liver Disease Subtypes—From Etiological Classification to Biological Phenotyping: Authors' Reply
Takao Miwa, Bernd Schnabl
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A 12-week home-based exercise program with nutritional guidance is associated with improved functional capacity in chronic liver disease
Shinji Unome, Takao Miwa, Yoshihiko Atago, Satomi Nakashima, Kayoko Nishimura, Shinya Hiraoka, Masashi Aiba, Kenji Imai, Yohei Shirakami, Koji Takai, Takaaki Aoki, Masahito Shimizu
Clinical Nutrition ESPEN.2026; 75: 105073. CrossRef

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

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

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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
Beyond BMI: Reassessing the Prevalence of Obesity in Patients With MASLD Under the Lancet Commission Diagnostic Criteria
Ru‐Tao Lin, Ren‐Qiang Zeng, Xu‐Ting Shen, Qin‐Mei Sun, Xin Xin, Jia‐Mei Chen, Yi‐Yang Hu, Qin Feng
Diabetes, Obesity and Metabolism.2026; 28(8): 6699. CrossRef
Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression
Ludovico Abenavoli, Anna Giulia Loricchio, Ivo Lopez, Domenico Morano, Abdulrahman Ismaiel, Dan Lucian Dumitrascu, Francesco Luzza
Medicina.2026; 62(5): 986. CrossRef
Estimated Body Fat Percentage and Triglyceride‐Glucose Index for Identifying MASLD in Lean Asian Adults: A Cross‐Sectional Analysis
Xiang‐Ran Kong, Ya‐Li Chen, Rui Li, Lu‐Xiang Shang, Sha Sha
The Kaohsiung Journal of Medical Sciences.2026;[Epub] CrossRef
MASLD and its lean phenotype
Kateřina Janstová, Denisa Kyselová, Pavel Trunečka
Vnitřní lékařství.2026; 72(4): 232. CrossRef

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Ethanol‑specific stress and RAB25/GCN1 signaling: Emerging perspectives in alcohol‑associated liver disease: Editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”: Miaomiao Wu, Qianying Cheng, Li Zuo, Hua Wang; Clin Mol Hepatol 2026;32(3):1394-1396.
Published online December 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.1360

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RAB25 as a liver-selective modulator of endoplasmic reticulum stress in alcohol-associated liver disease: Correspondence to editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”
Zi-Bin Zhan, Xue-Wen Liu, Ze-Hua Li, Fan-Hong Zeng, Kun-Hao Bai, Jun Weng
Clinical and Molecular Hepatology.2026; 32(3): e354. CrossRef

1,337 View
53 Download
1 Web of Science
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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

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Correspondence to editorial on “Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host-microbe signaling and highlights 2-hydroxyisocaproate as a potential effector”
Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Clinical and Molecular Hepatology.2026; 32(3): e361. CrossRef

1,153 View
48 Download
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Mechanistic insights into a noncanonical RAB25-GCN1 axis in ALD: Editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”: Seol Hee Park, Wonhyo Seo; Clin Mol Hepatol 2026;32(3):1390-1393.
Published online December 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.1346

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Correspondence to editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”
Xue-Wen Liu, Zi-Bin Zhan, Yu Gong, Ze-Hua Li, Kun-Hao Bai, Jun Weng
Clinical and Molecular Hepatology.2026; 32(3): e349. CrossRef
Reply to correspondence on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”
Seol Hee Park, Wonhyo Seo
Clinical and Molecular Hepatology.2026; 32(3): e432. CrossRef

1,155 View
41 Download
2 Web of Science
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Berberine and the gut microbiota - A novel treatment strategy for cholestatic liver disease: Editorial on “Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production”: Sung-Min Won, Ki Tae Suk; Clin Mol Hepatol 2026;32(3):1397-1399.
Published online December 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.1329

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Correspondence to editorial on “Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production”
Dianji Tu, Cheng Lu, Bo Tang, Shiming Yang
Clinical and Molecular Hepatology.2026; 32(3): e358. CrossRef

1,288 View
76 Download
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Novel biomarkers for alcohol-associated liver disease and their implications across clinical settings: Kaanthi Rama, Vinay Jahagirdar, Francisco Idalsoaga, Hanna Blaney, S. Fisher Rhoads, Luis Antonio Díaz, Marco Arrese, Juan Pablo Arab; Clin Mol Hepatol 2026;32(2):443-463.
Published online November 25, 2025; DOI: https://doi.org/10.3350/cmh.2025.0921

Abstract
PDF

Alcohol-associated liver disease (ALD) is a leading cause of preventable cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality, yet current laboratory and imaging tools detect only late-stage disease. This narrative review synthesizes emerging evidence on novel biomarkers that capture the multidimensional pathophysiology of ALD and discusses their utility for routine clinical practice. Traditional serum-based liver fibrosis markers (e.g., cytokeratin-18 fragments, Pro-C3, the enhanced liver fibrosis test) improve non-invasive staging risk beyond aminotransferases, while elastography techniques, such as vibration-controlled transient elastography and magnetic resonance elastography, can also quantify liver stiffness with high precision. Among novel mechanistic biomarkers, genetic polymorphisms in PNPLA3, TM6SF2, MBOAT7, HSD17B13, and polygenic risk scores define lifetime risk, whereas sex-specific hormonal milieus also modify susceptibility and progression. Moreover, gut dysbiosis signatures, including reduced Faecalibacterium prausnitzii, Akkermansia muciniphila, and a lower Firmicutes/Bacteroidetes ratio, and their metabolites (short-chain fatty acids, and bile acids, trimethylamine N-oxide) correlate with liver inflammation and fibrosis. Endocrine imbalances of cortisol, testosterone, and thyroid hormones further stratify metabolic vulnerability. Ultimately, multi-omics platforms (i.e., transcriptomics, lipidomics, proteomics, metabolomics, and epigenomics) can reveal distinct molecular signatures that predict steatohepatitis, fibrogenesis, and early HCC. Integrating these biomarkers enables phase-specific enrichment strategies, earlier intervention windows, adaptive dose-finding, and mechanismbased endpoints in ALD trials. Remaining challenges include assay standardization, validation across diverse cohorts, and incorporation into regulatory frameworks. Future work could evaluate cost-effectiveness and feasibility in routine clinical practice. Widespread adoption promises earlier diagnosis, personalized risk reduction, and more efficient drug development for this globally prevalent disorder.

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Dendrobium nobile Lindl. alleviates acute alcoholic liver injury in mice by modulating bile acid metabolism via the enterohepatic circulation
Di Wu, Qingping Yang, Ju Ye, Xuelan Chen, Xingdong Wu, Lin Qin, Yanliu Lu, Daopeng Tan, Yuqi He
Journal of Ethnopharmacology.2027; 373: 122310. CrossRef
Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation
Senping Xu, Zhaoshan Zhang, Zhongquan Zhou, Jiawei Guo
Biology.2026; 15(2): 148. CrossRef
Review Article on: AI-Driven Precision Medicine in Liver Disease: Microbiome and Nanotechnology Integration
Rahul Kumar, Amritesh Kumar, Aayush Kumar Tiwari, MD Nasiruddin Khan, Mohit Kumar, Moidul Islam Judder
Pan-African Journal of Health and Psychological Sciences.2026;[Epub] CrossRef
N-acetylcysteine for patients with alcohol use disorder, post-traumatic stress disorder, and their co-occurrence: a systematic review of placebo-controlled randomized trials
Mohamed Awad E. Ahmed, Mufreh Amin, Yomna Emad Abdalla, Amr Abdelghani, Nourhan Eid, Aya Samy, Omar Kassar, Khalid Radwan Alsaadany, Mohamed Ezzat M. Mansour
BMC Psychiatry.2026;[Epub] CrossRef
Correspondence to editorial on “RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression”
Xue-Wen Liu, Zi-Bin Zhan, Yu Gong, Ze-Hua Li, Kun-Hao Bai, Jun Weng
Clinical and Molecular Hepatology.2026; 32(3): e349. CrossRef
Biomarkers From the Microbiome to Predict ALD Progression and Its Severity: A Comprehensive Review
Suraj Mishra, Harshrajsinh Solanki, Palash Mandal, Jasbir Arora
Mediators of Inflammation.2026;[Epub] 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.
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.

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Targeting ferroptosis to halt MASLD and MASH
Fudi Wang
Trends in Endocrinology & Metabolism.2026; 37(8): 736. CrossRef

4,565 View
297 Download
6 Web of Science
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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.
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.

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Are FIB-4 and liver stiffness measurement interchangeable for HCC risk stratification in MASLD?
Yimeng Zhou, Xue Meng
JHEP Reports.2026; 8(8): 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
Hepatology: Emerging Paradigms in MASLD, Viral Hepatitis, Cholestatic Liver Disease, Portal Hypertension and Hepatocellular Carcinoma
Zobair M. Younossi, George Papatheodoridis, Emmanuel Tsochatzis, Maria Buti, Lorenza Rimassa, Massimo Pinzani, Ana Lleo, Debbie Shawcross, Frank Tacke, Vincent Wai‐Sun Wong, Shira Zelber‐Sagi, Andreas E. Kremer, David J. Pinato, Josep M. Llovet, Paolo Ang
Liver International.2026;[Epub] CrossRef

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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.
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.

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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

3,676 View
165 Download
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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.
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.

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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

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Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production: Dianji Tu, Cheng Lu, Junfeng Guo, Qiao Chen, Xin Li, Yingjie Wang, Lulu Cheng, Hongfei Jiang, Jincheng Jian, Yusong Ge, Zhanjie Hou, Xiaojie Feng, Yunxuan Feng, Jianchun Zhou, Yuanyuan Lei, Hua Diao, Lei Ran, Yuanyuan Zhou, Zhengguo Xu, Jiyin Zhou, Bo Tang, Shiming Yang; Clin Mol Hepatol 2026;32(1):221-238.
Published online October 14, 2025; DOI: https://doi.org/10.3350/cmh.2025.0577

Background/Aims
Cholestatic liver disease (CLD) is a pathological condition characterized by impaired bile formation, secretion, and excretion. However, the key pathophysiological mechanisms of CLD remain elusive, and therapeutic efficacy is unsatisfactory.
Methods
We administered berberine (BBR) or dihydroberberine (dhBBR) in bile duct ligation-, ANIT-, and mdr2^-/- CLD mouse models to evaluate the anti-CLD effect. We conducted fecal microbiota transplantation to determine the role of gut microbiota in BBR’s effect. We conducted a randomized, controlled clinical trial to evaluate the effects of BBR in patients with CLD.
Results
Oral BBR alleviates cholestatic liver injury in multiple mouse models. Gut microbes can transform BBR into dhBBR, which suppresses 5-hydroxytryptamine (5-HT) production in gut enterochromaffin cells by antagonizing tryptophan hydroxylase 1 (TPH1) activity and downregulating Tph1 transcription. This further ameliorates CLD by interrupting the 5-HT/5-HTR axis. A clinical study validated that BBR improved blood biochemical indicators in patients with CLD and decreased 5-HT levels.
Conclusions
BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.

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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

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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

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1,412 View
45 Download

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

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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
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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
Clinical and Molecular Hepatology.2026; 32(3): e342. CrossRef

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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

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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
Clinical and Molecular Hepatology.2026; 32(3): e339. CrossRef

2,474 View
90 Download
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RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression: Xue-Wen Liu, Zi-Bin Zhan, Ze-Hua Li, Yue Zhang, Xue-Yan Qiao, Xin-Ming Li, Xiang-Jing Liang, Kun-Hao Bai, Xian-Feng Xia, Fan-Hon Zeng, Yi Gao, Jun Weng; Clin Mol Hepatol 2026;32(1):200-220.
Published online September 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0559

Background/Aims
Endoplasmic reticulum (ER) stress in hepatocytes plays a causative role in alcohol-associated liver disease (ALD). The incomplete inhibition of ER stress by targeting canonical ER stress sensor proteins suggests the existence of noncanonical ER stress pathways in ALD pathology. This study aimed to delineate the role of RAB25 in ALD and its regulatory mechanism in noncanonical ER stress pathways.
Methods
RAB25 activation was examined in liver samples from ALD patients and ethanol-fed mice. The interaction between RAB25 and GCN1 was confirmed through mass spectrometry and co-immunoprecipitation (Co-IP) assays in vitro. The role of RAB25/GCN1 in promoting noncanonical ER stress in ALD was assessed both in vitro and in vivo.
Results
RAB25 expression was upregulated and specifically accumulated on the ER in ALD. Mass spectrometry and Co-IP assays confirmed that RAB25 interacts with GCN1, thereby activating a noncanonical ER stress pathway that facilitates ALD progression. Further analysis revealed that RAB25 interaction with GCN1 inhibits K33-ubiquitination-mediated degradation of GCN1, promotes GCN2 phosphorylation, and subsequently activates ATF4-mediated ER stress. This activation modulates lipid metabolism, mitochondrial function, and inflammation, thereby facilitating ALD progression. Knockdown of RAB25 in hepatocytes inhibited ER stress activation and mitigated associated mitochondrial dysfunction, excessive lipid synthesis, and the exaggerated inflammatory response in an ALD model.
Conclusions
Our findings demonstrate a causal role for RAB25-GCN1 signaling in activating the ER stress pathway, which contributes to ALD progression. This pathway may provide a proof-of-concept target for treating ALD and associated metabolic disorders.

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Sesaminol Ameliorates Metabolic and Alcohol‐Related Liver Injury by Activating the PPARα/Slc27a5 Axis‐Driven Hepatic Fatty Acid β‐Oxidation
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Molecular Nutrition & Food Research.2026;[Epub] CrossRef

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Correspondence to letter to the editor on "Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States": Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(3):e399-e401.
Published online September 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0948

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SAFE score in chronic liver diseases: A tool for risk enrichment and personalized surveillance: Correspondence to 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”: Tung-Hung Su, Jia-Horng Kao; Clin Mol Hepatol 2026;32(3):e396-e398.
Published online September 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0940

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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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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
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Li He, Yang Ye
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Naomi-Adina Ciurea, Laura Mahdi, Annarita Graziani, Agostino Di Ciaula, Piero Portincasa, Mohamad Khalil
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Gut Microbiota–Metabolite Alterations Associated with Early Metabolic Dysfunction and Hepatic Steatosis in Adolescents
Natalia Zeber-Lubecka, Paweł Czarnowski, Joanna Ziemska-Legięcka, Aldona Wierzbicka-Rucińska, Wojciech Jańczyk, Jacek Michałkiewicz, Łukasz Obrycki, Mieczysław Litwin, Michał Mikula, Piotr Socha, Jerzy Ostrowski
Computational and Structural Biotechnology Journal.2026;[Epub] CrossRef

10,248 View
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5 Web of Science
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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

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3,137 View
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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

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SAFE score in chronic liver diseases: A tool for risk enrichment and personalized surveillance: Correspondence to letter to the editor on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatiti
Tung-Hung Su, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(3): e396. CrossRef

3,880 View
36 Download
1 Web of Science
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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.
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.

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Clinical and Molecular Hepatology.2026; 32(3): e339. CrossRef
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Dongqin Yang, Yuli Lin, Chunhua Song, Ming Guan
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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
Clinical and Molecular Hepatology.2026; 32(3): 1379. CrossRef
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ASB3 limits adipocyte thermogenesis and energy expenditure through p62 ubiquitination
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Contemporary trends in extrahepatic mortality of chronic liver disease in the United States from 2014 to 2023: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed; Clin Mol Hepatol 2026;32(1):e24-e28.
Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0802

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