Clinical and Molecular Hepatology

Toward AI Virtual Cells for Hepatology: Representation, Generation, Dynamics, and Intervention in Single-Cell Models: Youngseok Choi, In Gyeong Koh, Murim Choi, Joon-Yong An, on behalf of the VITAL Consortium; Received June 29, 2026 Accepted September 9, 2026 Published online September 17, 2026; DOI: https://doi.org/10.3350/cmh.2026.0820 [Accepted]

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``Single-cell and spatial atlases describe the healthy and diseased liver at high resolution, including lobular hepatocyte zonation, fibrotic macrophage-stellate niches, cholangiocyte reactions, immune remodeling, and hepatocellular carcinoma ecosystems. These maps show where cell states occur but do not, by themselves, predict whether liver injury will progress or how the liver will respond to an untested drug, toxicant, or genetic perturbation. In this review, we organize current approaches toward an AI Virtual Cell (AIVC) for the liver into three complementary modeling routes. Generative models represent cell states, dynamics and transport models infer state transitions, and pretrained or foundation models test whether learned representations transfer across donors, etiologies, disease stages, and platforms. Perturbation-response prediction serves as a cross-cutting assessment of whether these layers can predict responses to untested genetic, chemical, inflammatory, or metabolic interventions. Available evidence can be categorized as direct liver validation, liver-included benchmarks, general single-cell evidence, and conceptual applications. Published models demonstrate individual components, including atlas integration, inferred trajectories, transferable representations, and retrospective response programs. However, these models do not constitute a prospectively validated liver simulator. At minimum, evaluation should include donor-, etiology-, stage-, platform-, and perturbation-level hold-outs. Model performance should be reported using response direction, recovery of differentially expressed genes and rare states, and calibrated uncertainty. Claims about tissue- or function-level prediction additionally require independent spatial, histologic, metabolic, and functional readouts. Near-term use should prioritize experiment selection and hypothesis generation, whereas clinical decision support remains a longer-term objective.

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Hepatocyte Plasticity in Liver Health and Disease: Zonation, Regeneration, Lineage Conversion, and Hepatic Malignancy: Xuan Wang, Yunfang Wang, Shuyong Wang; Received May 19, 2026 Accepted September 9, 2026 Published online September 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0630 [Accepted]

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Hepatocytes are highly specialized epithelial cells that maintain liver metabolic homeostasis, yet they also display remarkable plasticity in response to physiological demands, injury, disease, and oncogenic stress. In this review, we propose hepatocyte plasticity as an integrative framework that links homeostatic metabolic zonation, injury‑ and disease‑induced zonal remodeling and regeneration, hepatobiliary lineage conversion, and zonally biased malignant transformation. We first delineate homeostatic liver zonation as the baseline spatial architecture that constrains, rather than itself constitutes, hepatocyte plasticity, whereas dynamic re-zonation and state conversion represent plastic responses to perturbation. We further propose a conceptual framework that categorizes these plastic responses into four distinct yet interconnected modalities: transient adaptive state transitions, partial lineage conversion, transdifferentiation, and malignant lineage switching. We delineate the multiscale regulatory mechanisms underpinning each category, and critically assess the translational gaps between murine models and human disease. We further explore the therapeutic duality of this plasticity, evaluating emerging approaches that seek either to exploit its regenerative potential for liver repair and disease regression, or to counteract its pathological roles in cancer progression. By integrating these insights, this review establishes a comprehensive framework for understanding hepatocyte plasticity as a central determinant of liver pathobiology and highlights its translational potential for precision therapeutics in liver disease and cancer.

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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers: Won Kim; Clin Mol Hepatol 2026;32(Suppl):e2026.1072.
Published online September 1, 2026; DOI: https://doi.org/10.3350/cmh.2026.1072

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Alcohol-aware risk stratification and subtype-specific care pathways across metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease: Hyo Young Lee, Eileen Laurel Yoon, Dae Won Jun; Clin Mol Hepatol 2026;32(Suppl):e2026.0659.
Published online August 14, 2026; DOI: https://doi.org/10.3350/cmh.2026.0659

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Accurate classification and risk stratification across metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (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, 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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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef

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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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Steatotic liver disease: non-invasive assessment and biomarkers across metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatotic liver disease with moderate alcohol consumption and alcohol-associated liver disease: Monica Tincopa, Rohit Loomba; Clin Mol Hepatol 2026;32(Suppl):e2026.0415.
Published online July 15, 2026; DOI: https://doi.org/10.3350/cmh.2026.0415

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Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide impacting more than 30% of the adult population. With the rise of obesity, metabolic syndrome and alcohol use disorder, the prevalence of the two main subtypes of SLD - metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) - continues to increase. There has concurrently been an acknowledgement of a third subtype of SLD-metabolic dysfunction-associated steatotic liver disease with moderate alcohol consumption (MetALD)- wherein an individual has both components of metabolic dysfunction and regular alcohol intake. The public health significance of the SLD epidemic is substantial given risk for progression to cirrhosis, end-stage liver disease and development of hepatocellular carcinoma. Individuals with stage two fibrosis or above and those with active inflammation with hepatocyte injury are at highest risk for adverse liver-related outcomes and overall mortality. Current screening and risk stratification recommendations highlight the importance of identifying individuals at highest risk of clinical outcomes using non-invasive testing (NIT) as these individuals would benefit from liver-directed pharmacotherapy. Importantly, the performance of NITs can vary substantially based on NIT selected, cut points applied and patient population evaluated. The evidence base for NIT performance is strongest in MASLD with comparatively limited data in ALD and emerging data in MetALD. This review discusses NIT diagnostic performance in SLD and their role in chronic disease management.

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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef
Alcohol-aware risk stratification and subtype-specific care pathways across metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease
Hyo Young Lee, Eileen Laurel Yoon, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0659. CrossRef

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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]

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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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The hepatic portal area in homeostasis and disease: Fanrong Kong, Sara Lemoinne, Chantal Housset, Xinwei Li, Lin Lei; Clin Mol Hepatol 2026;32(3):1467-1471.
Published online July 1, 2026; DOI: https://doi.org/10.3350/cmh.2026.0662

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Chronic viral hepatitis with concurrent metabolic dysfunction-associated steatotic liver disease: dual etiology challenges: Shang-Chin Huang, Yi-Fen Shih, Chun-Jen Liu; Clin Mol Hepatol 2026;32(Suppl):e2026.0387.
Published online June 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0387

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The overlapping epidemics of chronic viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD) present a complex challenge in modern hepatology. In chronic hepatitis B, a unique “steatosis paradox” emerges: while isolated hepatic steatosis provides a suppressive microenvironment that promotes hepatitis B viral clearance, the concomitant systemic cardiometabolic burden acts dose-dependently to drive fibrogenesis and hepatocellular carcinoma (HCC). Conversely, chronic hepatitis C and host metabolic dysfunctions exhibit synergistic destruction. Hepatitis C virus actively hijacks lipid metabolism and induces insulin resistance. Even after viral eradication via direct-acting antivirals, residual steatosis and glycemic abnormalities remain formidable drivers of HCC. Consequently, the traditional virocentric paradigm is no longer sufficient. Clinical management should pivot toward precision risk stratification and a multidisciplinary dual-target approach, equally prioritizing sustained viral suppression and aggressive metabolic remission. This review summarizes the divergent virus-MASLD interactions, optimal clinical strategies, current challenges and future opportunities.

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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef

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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]

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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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How to apply artificial intelligence (AI) to facilitate and enhance MASH trials
Daniel Yan Zheng Lim, Wei Qiang Leow, Daniela S. Allende, Wai Kay Seto, Terry Cheuk-Fung Yip, George Boon Bee Goh
Hepatology International.2026;[Epub] CrossRef

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NAT10 deficiency in aging drives impaired liver regeneration by disrupting PARP10 in an ac4C-dependent manner: Qiang You, Cuicui Xiao, Haoqi Chen, Gongming Zhang, Feng Zhang, Zhengqi Wu, Yasong Liu, Jiebin Zhang, Haitian Chen, Jiaqi Xiao, Wenjie Chen, Jia Yao, Yingcai Zhang, Hua Li, Hui Li, Yang Yang, Rong Li, Jun Zheng; Received March 14, 2026 Accepted June 14, 2026 Published online June 18, 2026; DOI: https://doi.org/10.3350/cmh.2026.0244 [Accepted]

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Background & aims
The age-related decline in liver regenerative capacity worsens outcomes for elderly patients with liver disease or undergoing liver surgery, and therapeutic options are limited. The RNA modification N4-acetylcytidine (ac4C), catalyzed by N-acetyltransferase 10 (Nat10), is implicated in regeneration; however, its role in the aged liver remains unknown.
Methods
We quantified Nat10/ac4C levels in human and murine livers across ages and correlated them with regenerative capacity. Function was assessed via hepatocyte-specific knockout, adeno-associated virus (AAV)-mediated gene manipulation, and pharmacological inhibition. Mechanisms were defined using integrated ac4C-specific immunoprecipitation sequencing (ac4C-seq), ribosome profiling (Ribo-seq), and RNA sequencing (RNA-seq).
Results
Hepatic Nat10 and ac4C levels decreased with age. Disruption of Nat10/ac4C impaired liver regeneration, whereas their augmentation enhanced it. Multi-omics integration linked ac4C to coordinated changes in mRNA abundance, stability, and translation. Mechanistically, Nat10 installed ac4C on Parp10 mRNA to enhance its stability and translational efficiency. Upregulated Parp10 inhibited GSK3β, thereby activating pro-regenerative β-catenin signaling. Furthermore, we identified the age-related decline in Nat10 was attributed to loss of its transcriptional driver, ATF3. Pharmacological induction of ATF3 restored Nat10 expression and rescued regeneration in aged liver.
Conclusion
Our study highlights the critical role of Nat10 in liver regeneration via mRNA ac4C-manner and identifies its age-related decline as a reversible impairment. Targeting this presents a promising therapeutic strategy for stimulating regeneration in the aged liver.

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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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Precision pathophysiology in steatotic liver disease: Wonseok Lee, Da Kyung Hwang, Hyun Young Kim, David A. Brenner; Clin Mol Hepatol 2026;32(Suppl):e2026.0490.
Published online June 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0490

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Steatotic liver disease (SLD) comprises metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and alcohol-associated liver disease (ALD), which represent subclasses of liver disorders with overlapping etiologies. MASLD is defined as SLD with cardiometabolic dysfunction, whereas MetALD refers to MASLD with moderate alcohol consumption (140–350 g/week in females and 210–420 g/week in males). Despite being classified as distinct entities, MASLD and MetALD exhibit substantial phenotypic overlap, underscoring the need to delineate their pathological and molecular features and to develop models that capture the synergistic effects of alcohol and metabolic stress. Recent advances in multi-omic technologies have enabled integrated single-cell profiling of genetic, epigenetic, spatial, and proteomic features, providing high-resolution insights into cellular heterogeneity and disease mechanisms. In this review, we examine the pathophysiological landscape of SLD, highlight key distinctions between MASLD and MetALD, and discuss experimental models, including human liver spheroids. These approaches provide deeper insights into disease classification and accelerate the development of targeted therapies.

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The impact of alcohol consumption on the risk of hepatocellular carcinoma across different age groups: A nationwide cohort study
Mi Na Kim, Kyungdo Han, Dong Yun Kim, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim
JHEP Reports.2026; 8(10): 101975. CrossRef
Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef

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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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Cardiovascular and hepatic outcomes: prognostic differences across MASLD-MetALD-ALD continuum: Han Ah Lee, Gi-Ae Kim, Won Kim; Clin Mol Hepatol 2026;32(Suppl):e2026.0367.
Published online May 8, 2026; DOI: https://doi.org/10.3350/cmh.2026.0367

Abstract
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A paradigm shift in fatty liver disease nomenclature has introduced steatotic liver disease (SLD) as an umbrella term, encompassing metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD). These SLD subtypes exist along a dynamic continuum shaped by the synergistic interplay of metabolic dysfunction and alcohol exposure. Accumulating evidence indicates that SLD exhibits distinct outcome-based clusters reflecting heterogeneity in pathogenic drivers and clinical trajectories. Cardiometabolic clusters, most prominently observed in MASLD, are characterized by systemic metabolic dysfunction and confer increased risks of cardiovascular disease (CVD). In contrast, liver-specific clusters demonstrate progressive fibrosis and cirrhosis, hepatic decompensation, and hepatocellular carcinoma. In large-scale cohorts, CVD accounts for 40-50% of deaths in MASLD, while liver-related mortality predominates in ALD (>60%). The relative dominance of cardiometabolic versus liver-specific clusters shifts progressively across the MASLD-MetALD-ALD spectrum. While CVD remains a major driver of mortality, particularly in MASLD, hepatic outcomes increase stepwise with advancing fibrosis and greater alcohol exposure. Advanced fibrosis is the predominant shared determinant amplifying both CVD and hepatic risks across subtypes. This review synthesizes cardiovascular and hepatic outcome patterns across the MASLD-MetALD-ALD spectrum, highlighting the prognostic reorientation across the continuum, in which hepatic outcomes rise stepwise with alcohol exposure while cardiovascular risk remains an important but less subtype-differentiated burden. These findings advocate outcome-oriented risk stratification integrating noninvasive fibrosis assessment, alcohol biomarkers (phosphatidylethanol), and cardiovascular risk calculators within the cardiovascular-kidney-metabolic framework. Understanding SLD as a modifiable continuum enables individualized management to optimize multisystem outcomes.

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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef
Alcohol-aware risk stratification and subtype-specific care pathways across metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease
Hyo Young Lee, Eileen Laurel Yoon, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0659. CrossRef
Cardiovascular Complications of Chronic Liver Disease
Seong Park, Deepak K. Gupta, Manhal Izzy, Lisa B. VanWagner
Circulation.2026; 154(15): 1518. CrossRef

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Therapeutic landscape evolution for steatotic liver disease: from lifestyle interventions to precision pharmacotherapy: Shirley Huey Shin Bong, Kevin Kim Jun Teh, Vincent Wai-Sun Wong; Clin Mol Hepatol 2026;32(Suppl):e2026.0125.
Published online April 3, 2026; DOI: https://doi.org/10.3350/cmh.2026.0125

Abstract
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Steatotic liver disease (SLD) is a growing global epidemic, with metabolic dysfunction-associated steatotic liver disease now the most common chronic liver disease worldwide and closely linked to adverse cardiovascular outcomes. Lifestyle modification remains the cornerstone of management, with the Mediterranean diet as the preferred dietary intervention and emerging evidence supporting additional dietary and exercise strategies. Pharmacotherapy has advanced rapidly in recent years, with two U.S. Food and Drug Administration-approved options, resmetirom and semaglutide, for noncirrhotic metabolic dysfunction-associated steatohepatitis with moderate-to-advanced fibrosis, alongside multiple agents in development targeting different disease mechanisms. In metabolic dysfunction- and alcohol-associated liver disease, evidence remains limited, but management essentially focuses on alcohol cessation and optimization of cardiometabolic risk factors, with resmetirom, incretin-based therapies, and fibroblast growth factor-21 analogues representing promising therapeutic agents that have yet to be fully evaluated in clinical trials. The field is increasingly moving toward a precision medicine paradigm integrating pharmacologic and lifestyle interventions, tailored to disease phenotype, genetic risk, and gut microbiome. Key challenges include heterogeneity in treatment response, assessment of alcohol intake, and real-world implementation barriers. This review summarizes current and emerging therapies and highlights the role of precision medicine in advancing individualized care across the SLD spectrum.

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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef
Alcohol-aware risk stratification and subtype-specific care pathways across metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease
Hyo Young Lee, Eileen Laurel Yoon, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0659. CrossRef

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Co-repression of Yap1 and Sox9 abrogates established cholangiocarcinoma by eliminating transcriptional compensation: Minwook Kim, Shikai Hu, Yoojeong Park, Joseph Kwon, Laura Molina, Li-Ju Wang, Jia-Jun Liu, Silvia Liu, Aatur Singhi, Yu-Chiao Chiu, Sungjin Ko; Clin Mol Hepatol 2026;32(3):1305-1320.
Published online April 3, 2026; DOI: https://doi.org/10.3350/cmh.2025.1170

Background/Aims
Intrahepatic cholangiocarcinoma (iCCA) represents an unmet clinical need due to its increasing incidence, aggressive biology, and limited treatment options. The extremely low-response rates to current systemic regimens and the emergence of adaptive resistance to targeted therapies underscore the urgent need for alternative therapeutic strategies. Given that the lineage-defining transcription factors SOX9 and YAP1 are central regulators of cholangiocyte and iCCA identity, we investigated their functional roles as potential therapeutic vulnerabilities across multiple preclinical models.
Methods
Patient tissue-microarray analysis, Sleeping Beauty hydrodynamic tail vein injection–based iCCA models, and Cre-mediated inducible gene deletion systems were used to investigate the roles of Sox9 and Yap1. Deep-learning– based prediction, RNA-seq, chromatin immunoprecipitation sequencing and immunohistochemistry analyses were performed to delineate transcriptional networks and downstream effectors associated with SOX9/ YAP1 signaling.
Results
Dual deletion of Sox9 and Yap1 effectively eradicated advanced iCCA while preserving intrahepatic bile ducts, regardless of oncogenic drivers. Mechanistically, SOX9 and YAP1 transcriptionally compensated for each other when one was absent, and ILF2 and MGAT5 were identified as key downstream effectors mediating this compensatory mechanism. Loss of Ilf2 and Mgat5 suppressed iCCA, whereas overexpression of Ilf2 following Sox9/Yap1 co-deletion restored tumor development, indicating that ILF2 can functionally substitute for YAP1 and SOX9 in sustaining iCCA.
Conclusions
Co-targeting SOX9 and YAP1 offers a promising and safe broad-spectrum preventive/therapeutic approach for iCCA, potentially overcoming resistance to YAP1 inhibition. The adaptive resistance mechanism identified may extend to other malignancies, providing insights for addressing the advanced resistance to YAP1-TEAD-directed therapies.

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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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Metabolic Dysfunction-Associated Steatotic Liver Disease and Outcomes in Atrial Fibrillation
Pojsakorn Danpanichkul, Yanfang Pang, Kwanjit Duangsonk, Nithila Sivakumar, Primrose Tothanarungroj, Ahmad Anouti, Matheus Souza, Omar Y. Mousa, Thomas G. Cotter, Donghee Kim, Suthat Liangpunsakul, Chayakrit Krittanawong, Mazen Noureddin
The American Journal of Medicine.2026;[Epub] CrossRef

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From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease: Gyu Jeong Cho, Sun Myoung Kim, Yoon Mee Yang, Ekihiro Seki; Clin Mol Hepatol 2026;32(3):1135-1157.
Published online March 25, 2026; DOI: https://doi.org/10.3350/cmh.2025.1389

Abstract
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Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently gained attention as a risk factor for primary liver cancer and extrahepatic cancers. Increasing evidence shows that MASLD creates a fibrotic, immunosuppressive tumor microenvironment that supports metastatic growth, making it a risk factor for liver metastasis from extrahepatic tumors, such as colorectal cancer. In steatotic liver, tumor-stromal interactions promote colorectal liver metastasis through several mechanisms, including extracellular vesicles enriched with oncogenic microRNAs, hyaluronan synthase 2-mediated hyaluronic acid production by activated hepatic stellate cells and cancer-associated fibroblasts, M2-polarized tumor-associated macrophage infiltration, and Yes-associated protein-dependent tumor signaling. In this review, we summarize key pathways involved in a pre- and pro-metastatic niche in the liver, such as extracellular vesicle-mediated intercellular communication, feed-forward loops between tumor cells and stromal fibroblasts, and hyaluronic acid-induced extracellular matrix remodeling and immune cell modulation, all of which impair antitumor immunity and promote immune escape. We also discuss how targeting hyaluronic acid synthesis, interleukin-1 signaling, or CXCR2 can restore antitumor immunity and improve responses to programmed cell death protein-1 blockade. These therapeutic approaches may offer promising benefits for patients with colorectal cancer liver metastasis.

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Severe hepatitis B flare and liver failure: current assessment and management: Seng Gee Lim, Maria Buti, Jordan J. Feld, James Fung, Adam J. Gehring, K. Rajender Reddy; Clin Mol Hepatol 2026;32(3):1117-1134.
Published online March 18, 2026; DOI: https://doi.org/10.3350/cmh.2026.0177

Hepatitis B flare is a common complication of chronic hepatitis B and is defined as an increase in HBV viral load associated with abnormal alanine aminotransferases (ALT), the consensus being an ALT level ≥5 times the upper limit of normal. The immunopathogenesis is related to induction of inflammatory cells and cytokines by the rise in HBV DNA. There are multiple causes of flares, and they carry the risk of progression to hepatic decompensation and acute-on-chronic liver failure (ACLF) with associated mortality, potentially requiring liver transplantation. Initial assessment should exclude other causes of liver dysfunction and determine severity and prognosis. General prognostic models of ACLF are useful but the COSSH-ACLF II score is specific to HBV. Early initiation of nucleos(t)ide analogues is crucial, even in severe HBV flares; it can reduce mortality by 73.6%. Once jaundice and coagulopathy occur, salvage by antivirals is challenging, and liver transplantation should be considered. However, many patients may not be suitable candidates for transplant or donor livers may not be available, as is common in Asia. Recently, there has been increasing evidence of the benefits of adjunctive therapies such as corticosteroids and plasma exchange, but there are associated risks and these approaches should be considered rescue therapies in severe HBV flares or ACLF. Liver transplant is the ultimate intervention when these other strategies fail. In summary, HBV flares are clinically serious events that can lead to hepatic decompensation, ACLF, and the need for a donor liver; however, strategies for rescue should be considered before liver transplantation.

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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

1,609 View
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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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Hepatic steatosis: A pandemic disease causing serious secondary diseases
Ali Canbay, Anja Figge, Polykarpos C. Patsalis, Theodor Baars, Mustafa K. Özçürümez, Oliver Götze
Deutsches Ärzteblatt international.2026;[Epub] CrossRef

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From post-transplant outcomes to listing decisions: Clinical implications of comparing expanded hepatocellular carcinoma transplant criteria: Letter to the editor on “Network meta-analysis and validation study of expanded liver transplantation criteria for hepatocellular carcinoma: Significant role of alpha-fetoprotein”: Bo Ni, Hairui Wang; Clin Mol Hepatol 2026;32(3):e315-e316.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0124

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1,368 View
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Discordant FIB-4 and liver stiffness in metabolic dysfunction-associated steatotic liver disease: Toward clinically coherent risk stratification: 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”: Zhanna Zhang, Zichen Yu, Gongqiang Wu; Clin Mol Hepatol 2026;32(3):e297-e299.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0049

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Risk assessment in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-related liver disease: current approaches and future directions
Huapeng Lin, Haixia Wang, Kangsen Yang, Min Li, Yanting Wang, Terry Cheuk-Fung Yip, Seung Up Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0398. CrossRef

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Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions: Suqin Yang, Sunbin Ling, Jianhua Li, Yan Wang, Jiapei Wang, Qiwei Huang, Fanming Liu, Yiqi Zhuang, Yingyu Zheng, Rui Wang, Zhe Yang, Xiaoping Zheng, Kai Wang, Zhikun Liu, Jun Chen, Jianguo Wang, Haiyang Xie, Lin Zhou, Leiming Chen, Guoqiang Cao, Dandan Chen, Junfang Ji, Bin Zhao, Chao Jiang, Di Lu, Xuyong Wei, Hangjin Jiang, Qiaonan Shan, Hengbo Shi, Yong-Zhen Xu, Shusen Zheng, Zhengxin Wang, Shengda Lin, Xiao Xu; Clin Mol Hepatol 2026;32(2):884-903.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2025.1069

Background/Aims
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

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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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57 Download
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Reply to correspondence on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”: Shadi Zerehpoosh, Ziyan Pan, Mohammed Eslam; Clin Mol Hepatol 2026;32(3):e450-e452.
Published online February 5, 2026; DOI: https://doi.org/10.3350/cmh.2026.0133

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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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1,607 View
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National trends in resmetirom prescriptions for metabolic dysfunction-associated steatohepatitis in the USA: Brian P. Lee, Christopher Scannell, Matt Dukewich, Jennifer L. Dodge, Norah A. Terrault, Dima Mazen Qato; Clin Mol Hepatol 2026;32(2):e185-e188.
Published online February 5, 2026; DOI: https://doi.org/10.3350/cmh.2025.1414

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2,295 View
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Improving the choice of liver transplant for hepatocellular carcinoma: Editorial on “Network meta-analysis and validation study of expanded liver transplantation criteria for hepatocellular carcinoma: Significant role of alpha-fetoprotein”: Jongman Kim; Clin Mol Hepatol 2026;32(3):1461-1462.
Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0111

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Post-transplant hepatocellular carcinoma: balancing immunosuppression and immune checkpoint inhibitors: Tomoharu Yamada, Ryosuke Tateishi, Mitsuhiro Fujishiro; Clin Mol Hepatol 2026;32(2):580-598.
Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2025.1179

Abstract
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Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and hepatocellular carcinoma (HCC). Advances in surgical techniques and immunosuppressive regimens have markedly improved early post-transplant survival. However, long-term outcomes remain compromised by HCC recurrence, chronic rejection, metabolic complications, and de novo malignancies. Recurrence of HCC after LT remains a major clinical challenge, with available prognostic models providing limited accuracy in risk stratification. Simultaneously, systemic therapies for unresectable HCC have rapidly advanced, particularly with immune checkpoint inhibitors (ICIs), providing new opportunities and unique challenges in transplant settings. With ICIs carrying a risk of acute and potentially fatal rejection and lacking controlled data on efficacy or safety in the post-transplant setting, tyrosine kinase inhibitors currently represent a standard option for post-transplant recurrence. Novel biomarkers, such as donor-derived cell-free DNA and the gut microbiome, are emerging as potential tools to refine risk stratification and guide immunosuppression. Furthermore, innovative immunotherapies, including oncolytic viruses and mRNA vaccines, are being explored as tumor-specific approaches. Collectively, these advances may reshape future management of LT recipients.

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Risk factors and prevention strategies for recurrence of hepatocellular carcinoma after liver transplantation
Qing-Cheng Zhao, Jia-Ning Cui, Jia-Hang Li, Qiang Fu, Hong-Ji Yang, Shi-Kai Zhu
World Chinese Journal of Digestology.2026; 34(5): 361. CrossRef
Review Article: Biomarkers in Liver Transplantation for Hepatocellular Carcinoma: Towards Precision Medicine
Yule Ma, Huigang Li, Huan Chen, Jinxin Xu, Ziyi Ye, Yuhang Li, Xiang Wu, Jinyan Chen, Chenghao Cao, Peiru Zhang, Ruijie Zhao, Jun Li, Cheng Zhu, Jianyong Zhuo, Shengjun Xu, Xiao Xu, Di Lu
Alimentary Pharmacology & Therapeutics.2026; 64(4): 441. CrossRef
Drug-resistant bacterial infections in end-stage liver disease: immune imbalance and intervention advances
Jing Liu, Jun Wu, Xin Zheng
Frontiers in Immunology.2026;[Epub] CrossRef
Short- and long-term outcomes of liver transplantation in patients withbhepatocellular carcinoma
M. S. Novruzbekov, O. D. Olisov, I. A. Dzhanyan, V. A. Guliaev, V. V. Breder, V. E. Syutkin, K. N. Lutsyk
Annaly khirurgicheskoy gepatologii = Annals of HPB Surgery.2026; 31(3): 33. CrossRef

3,310 View
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Correspondence to letter to the editor on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”: Xinrui Jin, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip; Clin Mol Hepatol 2026;32(3):e422-e423.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0075

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Reply to correspondence on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”
Shadi Zerehpoosh, Ziyan Pan, Mohammed Eslam
Clinical and Molecular Hepatology.2026; 32(3): e450. CrossRef

1,278 View
12 Download
1 Web of Science
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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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1,320 View
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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

1,646 View
77 Download
1 Web of Science
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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; Clin Mol Hepatol 2026;32(3):e378-e380.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0038

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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
Clinical and Molecular Hepatology.2026; 32(3): e439. CrossRef

1,711 View
34 Download
1 Web of Science
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Correspondence to editorial 2 on “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis”: Hyunjae Shin, Moon Haeng Hur, Yoon Jun Kim; Clin Mol Hepatol 2026;32(3):e381-e383.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0037

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1,542 View
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Aspirin on the prevention of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: Editorial on “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: Nationwide cohort study with genetic risk analysis”: Teng-Yu Lee, Chun-Ying Wu; Clin Mol Hepatol 2026;32(3):1433-1436.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0007

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Correspondence to editorial 2 on “Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis”
Hyunjae Shin, Moon Haeng Hur, Yoon Jun Kim
Clinical and Molecular Hepatology.2026; 32(3): e381. CrossRef

1,878 View
60 Download
1 Web of Science
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Reconciling definitions, phenotypes and outcomes in lean metabolic dysfunction-associated steatotic liver disease: Editorial on “Normal-weight metabolic dysfunction-associated steatotic liver disease: Reclassification, characteristics, and adverse liver outcomes across diverse populations”: Shanshan Wu; Clin Mol Hepatol 2026;32(3):1437-1440.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0004

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MASLD and its lean phenotype
Kateřina Janstová, Denisa Kyselová, Pavel Trunečka
Vnitřní lékařství.2026; 72(4): 232. 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
Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations
Senlin Lei, Jiasheng Tao, Xiaoan Chen, Xianhui Li, Songwei Zhong
Lipids in Health and Disease.2026;[Epub] 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

1,541 View
18 Download
1 Web of Science
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A call for more efforts to incorporate liver in the metabolic health framework: Letter to the editor on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”: Shadi Zerehpoosh, Ziyan Pan, Mohammed Eslam; Clin Mol Hepatol 2026;32(3):e303-e305.
Published online January 14, 2026; DOI: https://doi.org/10.3350/cmh.2025.1427

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Reply to correspondence on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”
Shadi Zerehpoosh, Ziyan Pan, Mohammed Eslam
Clinical and Molecular Hepatology.2026; 32(3): e450. CrossRef
Correspondence to letter to the editor on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”
Xinrui Jin, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Clinical and Molecular Hepatology.2026; 32(3): e422. CrossRef

1,230 View
19 Download
2 Web of Science
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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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40 Download
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Hepatocellular carcinoma surveillance: a health economic evaluation: Qi-Feng Chen, Xiong-Ying Jiang, Song Chen, Jiongliang Wang, Ming Zhao; Clin Mol Hepatol 2026;32(2):536-564.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1060

Hepatocellular carcinoma (HCC) imposes a major health and economic burden worldwide, with disproportionate effects in low- and middle-income countries (LMICs). Surveillance in high-risk populations, typically using semiannual ultrasound and alpha-fetoprotein testing, has been shown to be cost-effective by enabling earlier detection and improving survival. Yet, its overall value is reduced by poor adherence and the limited sensitivity of ultrasound, particularly in patients with metabolic-associated steatotic liver disease. Emerging approaches—including abbreviated magnetic resonance imaging, multi-biomarker models (e.g., gender, age, AFP, AFP-L3, and DCP), and liquid biopsy assays such as methylated DNA markers—demonstrate greater diagnostic accuracy and potential economic advantages compared with conventional methods. Integration of artificial intelligence into imaging may further enhance efficiency and reduce downstream costs. Moving toward precision surveillance, guided by individualized risk stratification that incorporates etiology, fibrosis stage, and molecular profiles, can optimize allocation of resources and maximize cost-effectiveness at the population level. Interventions to improve adherence, including mailed outreach and behavioral economic incentives, have shown both clinical benefit and cost savings, underscoring the role of implementation science. Because socioeconomic disparities influence both access and outcomes, economic models must explicitly address equity to achieve sustainable impact. Future research should prioritize prospective trials that evaluate not only clinical performance but also the real-world cost-effectiveness of novel technologies and stratified surveillance strategies. For LMICs, adapting proven models into affordable, context-appropriate programs is essential. By combining prevention, precision risk assessment, innovative technologies, and equitable implementation, HCC surveillance can deliver both clinical and economic value, reducing the global burden of disease.

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Toward Precise Risk Stratification after the Functional Cure of Chronic Hepatitis B
Moon Haeng Hur
The Korean Journal of Gastroenterology.2026; 86(2): 71. CrossRef
Burden and Regional Disparities of MASH‐Related Liver Cancer in the Asia‐Pacific Region From 1990 to 2023
Xiao‐Dong Zhou, Qin‐Fen Chen, Daniel Q. Huang, Hung N. Luu, Giovanni Targher, Christopher D. Byrne, Huai Zhang, Mazen Noureddin, Renyi Su, Jacob George, Zobair M. Younossi, Frank Tacke, Ming‐Hua Zheng
Liver International.2026;[Epub] CrossRef
The impact of alcohol consumption on the risk of hepatocellular carcinoma across different age groups: A nationwide cohort study
Mi Na Kim, Kyungdo Han, Dong Yun Kim, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim
JHEP Reports.2026; 8(10): 101975. CrossRef

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Network meta-analysis and validation study of expanded liver transplantation criteria for hepatocellular carcinoma: Significant role of alpha-fetoprotein: Dongman Yu, Yeongseok Hwang, Jin-Sung Ju, Subin Heo, Seon-Ok Kim, Sang Hyun Choi, Gi-Won Song, Jihyun An, Ju Hyun Shim; Clin Mol Hepatol 2026;32(2):751-771.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.0986

Background/Aims
Various expanded criteria (EC) for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) have been proposed to avoid the narrow nature of the Milan criteria (MC). To investigate which EC predicts more favorable outcomes in terms of overall survival (OS) and recurrence-free survival (RFS), we conducted a network meta-analysis (NMA).
Methods
A database search was conducted on PubMed, Embase, and the Cochrane Library, to identify studies comparing OS and RFS between patients within the MC and those exceeding the MC but within the EC. Hazard ratios (HRs) were pooled using a random-effects NMA and validated in an in-house cohort of 1,008 LT recipients.
Results
Among 22,466 articles identified, 35 studies with 45 pairwise comparisons were included in the NMA along with 8 different EC. The University of California San Francisco (HR, 1.43; 95% CI, 1.19–1.71), Up-to-Seven (HR, 1.50; 95% CI, 1.15–1.97), and Hangzhou criteria (HR, 1.69; 95% CI, 1.11–2.57) showed inferior OS to the MC. The MC ranked highest for both OS and RFS, followed by Metroticket 2.0 for OS and the Asan criteria for RFS. In the validation cohort, both Metroticket 2.0 and AFP model yielded more favorable HCC-specific mortality than other EC.
Conclusions
Several EC, of which those of Metroticket 2.0 were the best, yielded comparable outcomes to the MC. AFP-based EC such as Metroticket 2.0 and AFP model appeared to be useful in both the NMA and the validation cohort, suggesting a potential role in identifying selected low-risk patients beyond the MC.

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Redefining Liver Transplantation Indications for Hepatic Malignancies in the Era of Precision Transplant Oncology: An Up-to-Date Narrative Review
Mario Romeo, Fiammetta Di Nardo, Carmine Napolitano, Paolo Vaia, Claudio Basile, Giusy Senese, Annachiara Coppola, Patrizia Iodice, Simone Olivieri, Alessandro Federico, Marcello Dallio
Journal of Clinical Medicine.2026; 15(10): 3579. CrossRef
Shrinking Giants: On the Feasibility of Downsizing Hepatocellular Carcinoma with Immunotherapy Prior to Liver Transplantation
Juraj Prejac, Domina Kekez, Hana Lučev, Borna Ćutić, Viktor Domislović, Vibor Šeša, Gordan Adžić, Marin Golčić
Journal of Clinical Medicine.2026; 15(10): 3923. CrossRef
Improving the choice of liver transplant for hepatocellular carcinoma: Editorial on “Network meta-analysis and validation study of expanded liver transplantation criteria for hepatocellular carcinoma: Significant role of alpha-fetoprotein”
Jongman Kim
Clinical and Molecular Hepatology.2026; 32(3): 1461. CrossRef
From post-transplant outcomes to listing decisions: Clinical implications of comparing expanded hepatocellular carcinoma transplant criteria: Letter to the editor on “Network meta-analysis and validation study of expanded liver transplantation criteria fo
Bo Ni, Hairui Wang
Clinical and Molecular Hepatology.2026; 32(3): e315. CrossRef
Risk Stratification of Hepatocellular Carcinoma Recurrence After Liver Transplantation: A 25-Year Single-Center Study Comparing Pre- and Post-Transplant Prognostic Models
Andrea González De Godos, Martín Bailón Cuadrado, Paloma Lourdes Rodríguez Vielba, Pilar Pinto Fuentes, David Pacheco Sánchez
Journal of Clinical and Experimental Hepatology.2026; : 103677. 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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