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]

Abstract
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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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External beam radiotherapy versus local ablation therapy for the treatment of hepatocellular carcinoma: a systematic review and meta-analysis: Sun Hyun Bae, Seo Hee Choi, Sang Min Yoon, Jeong Il Yu, Hyun-Cheol Kang, Nalee Kim, Tae Hyun Kim, Hee Chul Park; Received April 29, 2026 Accepted July 15, 2026 Published online July 30, 2026; DOI: https://doi.org/10.3350/cmh.2026.0535 [Accepted]

Abstract
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Background/Aims
Local ablation therapies (LATs), including radiofrequency (RFA) and microwave ablation (MWA), are established for small hepatocellular carcinoma (HCC) as standard treatment. External beam radiotherapy (EBRT), including stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT), has emerged as a non-invasive alternative; however, direct comparative evidence remains limited. We conducted a systematic review and meta-analysis comparing the efficacy and safety of EBRT versus LAT in patients with HCC.
Methods
PubMed/MEDLINE, Embase, Cochrane Library, and KoreaMed were searched through June 2025 per PRISMA guidelines. Eligible studies included retrospective or prospective comparisons of EBRT (SBRT/PBT) with LAT (RFA/MWA) reporting recurrence or survival. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random-effects models.
Results
Twelve studies (2,768) patients were included. Compared with LAT, EBRT was associated with significantly lower local recurrence (OR 0.36, 95% confidence interval [CI] 0.25–0.50; P<0.001; I² = 0%) and improved local progression-free survival (HR 0.41, 95% CI 0.34–0.50; P <0.001), regardless of tumor size. Progression-free survival favored EBRT (HR 0.80, 95% CI 0.64–1.00; P = 0.049), whereas overall survival did not differ significantly between modalities (HR 1.24, 95% CI 0.83–1.84; P = 0.291). Severe toxicities (grade ≥3) were comparable between groups for acute (OR 0.78, 95% CI 0.27–2.24) and late events (OR 1.29, 95% CI 0.85–1.95).
Conclusions
EBRT was associated with better local control without significant differences in survival or toxicity compared with LAT. These findings support the safety and efficacy of EBRT for local treatment of patients with liver-confined HCC.

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Global epidemiological patterns and disease burden of metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease: Pojsakorn Danpanichkul, Matheus Souza, Primrose Tothanarungroj, Aijaz Ahmed, Donghee Kim; Clin Mol Hepatol 2026;32(Suppl):e2026.0444.
Published online July 15, 2026; DOI: https://doi.org/10.3350/cmh.2026.0444

The 2023 multisociety Delphi consensus redefined the nomenclature for steatotic liver disease (SLD) by replacing nonalcoholic fatty liver disease with metabolic dysfunction-associated steatotic liver disease (MASLD) and introducing metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD). This revised framework is expected to enhance epidemiological surveillance, phenotyping of SLD, and public health interpretation. This review summarizes contemporary literature on the global epidemiology, disease burden, and comparative outcomes of MASLD, MetALD, and ALD. MASLD remains the most prevalent SLD subtype, affecting approximately 30–40% of adults worldwide, with a rising burden over time. MASLD rapidly increases in regions with lower sociodemographic indices. MetALD affects an estimated 2–8% of adults and represents an important overlap phenotype, although its prevalence is likely underestimated due to frequent underreporting of alcohol intake. ALD has a lower prevalence but contributes disproportionately to higher liver-related morbidity and mortality and is reported to have a marked regional variation linked to patterns of alcohol consumption. SLD has emerged as a major global epidemic, with MASLD imposing the greatest population burden and MetALD/ALD disproportionately contributing to severe liver-related outcomes. Across SLD phenotypes, cardiovascular disease is a major cause of death in non-cirrhotic disease, while liver-related outcomes show a gradient associated with alcohol exposure. Significant epidemiologic limitations include heterogeneity in the steatosis assessment methods, limited availability of cardiometabolic criteria, and reliance on self-reported alcohol consumption. Mitigating this growing burden of SLD requires public health policies that incorporate metabolic risk prevention, regulation of alcohol consumption, and early risk stratification.

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Placebo-Arm Cirrhosis Incidence in Fibrotic MASH: A Trial-Based Benchmark
Matheus Souza
Digestive Diseases and Sciences.2026;[Epub] CrossRef
Starving in Plenty: Recognizing Malnutrition in Steatotic Liver Disease
Hyun Hee Sul, Saeed Ahmad, Matheus Souza
Digestive Diseases and Sciences.2026;[Epub] CrossRef
Association of a Reported Penicillin Allergy Label With Clinical Outcomes in Alcohol‐Associated Liver Disease
Pojsakorn Danpanichkul, Yanfang Pang, Kanyaphak Charnpatanakorn, Preenapun Saokhieo, Ben Thiravetyan, Allan Bueso, Ahmad Anouti, Apichat Kaewdech, Surapon Nochaiwong, Luis Antonio Díaz, Juan Pablo Arab, Jonathan A. Bernstein, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2026;[Epub] 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
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
PNPLA3 Is Associated With Hepatocellular Carcinoma, While a Five‐Variant Polygenic Risk Score Shows Limited Discrimination in Korean Patients With MASLD
Jaejun Lee, Jung Hoon Cha, Hee Sun Cho, Hyun Yang, Mi Young Byun, Seok Keun Cho, Seong Wook Yang, Si Hyun Bae, Seung Up Kim, Su Jong Yu, Pil Soo Sung
Journal of Gastroenterology and Hepatology.2026;[Epub] 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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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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Clinical utility of liquid biopsy in biliary tract cancer: Diagnosis to treatment monitoring: Seonjeong Woo, Sohyun Hwang, Chan Kim, Hong Jae Chon; Received March 19, 2026 Accepted June 21, 2026 Published online June 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0337 [Accepted]

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Biliary tract cancer (BTC) represents a formidable clinical challenge characterized by extensive genomic heterogeneity and a poor prognosis, primarily due to advanced stage diagnosis. Although systemic therapies, including chemotherapy, targeted therapies, and immune checkpoint inhibitors, have become the standard of care, their efficacy remains modest, and subsequent treatment options are limited. BTC management is further complicated by the inherent difficulty of obtaining high-quality tissue biopsies, impeding timely genomic profiling and subsequent therapeutic decision-making. Liquid biopsy has emerged as a minimally invasive alternative, facilitating comprehensive tumor characterization through circulating tumor cells, cell-free DNA, RNA, and proteins. These approaches hold promise for early detection, assessment of minimal residual disease, identification of actionable targets, and real-time monitoring of treatment response and resistance, thereby supporting precision oncology. Despite technical challenges such as limited sensitivity for structural variations, variability across platforms, and the need for standardized validation, liquid biopsy offers transformative potential in BTC. This review discusses current strategies, clinical applications, and future directions for integrating liquid biopsy into routine practice to improve survival and quality of life in patients with BTC.

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Glutamate excreted by LepR⁺ BM-MSCs mitigates alcohol-associated liver disease by promoting IL-1R2⁺ monocyte migration: Young-Ri Shim, Hee-Hoon Kim, Min Jeong Kim, Jun-Hee Lee, Kyurae Kim, Sung Eun Choi, Katherine Po Sin Chung, Eunmi Lee, Kwang Woo Lee, Jihyo Byun, Jaewoo Oh, Jae Min Han, Jun Ho Byun, Jong-Eun Park, Won Kim, Young-Sun Lee, Won-Il Jeong; Received April 5, 2026 Accepted June 16, 2026 Published online June 18, 2026; DOI: https://doi.org/10.3350/cmh.2026.0425 [Accepted]

Abstract
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Background/Aims
Bone marrow mesenchymal stromal cells (BM-MSCs) exert diverse functions, including supporting alcohol detoxification and providing a niche for monocyte development. However, their role in regulating monocytes during alcohol-related liver disease (ALD) remains unclear. This study investigates how BM-MSCs orchestrate the egress of anti-inflammatory monocytes from BM to the liver in ALD.
Methods
Wild-type, leptin receptor (LepR)⁺ BM-MSC-specific Slc7a11 knockout, and natural killer (NK) cell-specific Grm5 knockout mice were fed an ethanol diet for 8 weeks. Tissue analyses were performed using single-cell RNA sequencing (scRNA-seq), immunostaining, and flow cytometry. Blood and liver samples from ALD patients were examined.
Results
scRNA-seq revealed a distinct population of BM-derived Ly6C^low hepatic macrophages expressing interleukin-1 receptor 2 (IL-1R2), an IL-1β decoy receptor, in ethanol-fed mice. In the BM, alcohol exposure upregulated the gene expression of alcohol-metabolizing enzymes (Adh1, Aldh2), xCT (Slc7a11), and chemokines (Cxcl9, Cxcl10) in LepR⁺ BM-MSCs, promoting NK cell recruitment and interferon-γ (IFN-γ) production via metabotropic glutamate receptor 5 (mGluR5) activation. Subsequently, IFN-γ enhanced IL-1R2 expression and suppressed CX₃CR1 in neighboring Ly6C^low BM monocytes, facilitating their hepatic migration. LepR⁺ BM-MSC-specific xCT and NK cell-specific mGluR5 knockout mice exhibited exacerbated liver injury and elevated blood IL-1β levels, while recombinant IL-1R2 administration improved ameliorated ALD in wild-type mice. Consistently, increased IL-1R2 levels were observed in plasma, CD14⁺CD16⁺ blood monocytes, and liver tissues of ALD patients.
Conclusions
We identified a BM-liver axis in which glutamate released by BM-MSCs activates mGluR5 in BM NK cells, driving IL-1R2⁺ monocyte migration to the liver and attenuating ALD progression.

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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

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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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Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease: Bingjie Ye, Chengfu Xu; Clin Mol Hepatol 2026;32(3):1158-1185.
Published online May 8, 2026; DOI: https://doi.org/10.3350/cmh.2026.0218

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Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disease worldwide and is closely linked to systemic metabolic disorders. In addition to their classical role in hemostasis, platelets are increasingly recognized as active regulators of inflammation and immune responses, yet their contribution to MASLD pathogenesis remains incompletely defined. This review synthesizes current knowledge on how metabolic disturbances and gut microbiota dysbiosis trigger platelet hyperactivation and intrahepatic recruitment. We examined the mechanisms by which activated platelets exacerbate steatosis, amplify inflammation through interactions with immune cells, promote fibrogenic remodeling through hepatic stellate cell activation, and contribute to hepatocarcinogenesis. In the context of MASLD-associated hepatocellular carcinoma, platelet involvement may occur through both inflammation/fibrogenic remodeling–mediated and direct tumor-regulatory mechanisms. Furthermore, the therapeutic potential of antiplatelet agents, particularly aspirin, in attenuating disease progression has been evaluated. We conclude that targeting platelet-related pathways may represent a promising therapeutic strategy to interrupt the interplay between metabolic dysfunction and liver injury in MASLD.

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Cognitive dysfunction in MASLD is linked to platelet activation
Jiaqin Chen, Chi Cheng, Haiying Wang, Tian Yu
Frontiers in Neuroscience.2026;[Epub] CrossRef

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Predictive modeling and clinical decision tools for risk stratification in steatotic liver disease: Jeanette Girard, Elliot B. Tapper, Vincent L. Chen; Clin Mol Hepatol 2026;32(Suppl):e2026.0204.
Published online April 24, 2026; DOI: https://doi.org/10.3350/cmh.2026.0204

Abstract
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatic decompensation and liver-related death, but most patients with MASLD do not develop these liver-related complications. Risk prediction and care pathways are crucial to identify which patients with MASLD are highest risk and link them to appropriate care. Risk prediction is usually done with blood-based algorithms such as Fibrosis-4, AST-platelet ratio index, and more recent scores such as steatosis-associated fibrosis estimator and LiverRisk Score. Second-line tests include enhanced liver fibrosis and imaging-based tests such as vibration-controlled transient elastography, shear wave elastography, or magnetic resonance elastography. We propose a consensus risk stratification care pathway that can be adapted for different clinical settings. We also discuss key needs to improve upon the state of the art: improving diagnosis/prognostic accuracy, especially of blood-based models, optimizing calibration, and ensuring interpretability of predictive models. Finally, we discuss recent advances in clinical decision support systems including best practice advisories, dashboards, and dynamic guidelines. We highlight factors critical to clinical decision support systems, including integration with existing systems and clinician workflows, minimizing additional burden to clinicians, provision of decision support and recommendations at the time/place of decision-making, and continuous evaluation and local user involvement.

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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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Lack of association between rifaximin and drug-resistant infections: a global multicenter inpatient cirrhosis cohort: Jasmohan S. Bajaj, Patrick S. Kamath, Florence Wong, Qing Xie, Ramazan Idilman, Mark Topazian, Wai-Kay Seto, Aldo Torre, Peter Hayes, Peter George, Mario Alvares-da-Silva, Brian J. Bush, Scott Silvey, Ashok Choudhury, on behalf of CLEARED Investigators; Clin Mol Hepatol 2026;32(3):1321-1332.
Published online April 15, 2026; DOI: https://doi.org/10.3350/cmh.2026.0228

Background/Aims
Infections with drug-resistant organisms (DROs) are associated with poor outcomes in cirrhosis. Rifaximin, widely used for hepatic encephalopathy (HE), could promote cross-resistance, but data regarding clinical impact are conflicting. Determine predictors of DROs in a global cirrhosis inpatient cohort focusing on preadmission rifaximin use.
Methods
From the global CLEARED consortium, we focused on cirrhosis inpatients with infections on/during admission. Clinical/demographic/medication, especially rifaximin details were recorded. The primary outcome was DRO development. Multivariable regression for DRO including clinical, medications, and country income was performed.
Results
2,949 infected inpatients (55.3 years, 62.9% male) were included. 12.2% of all and 24.4% of culture-positive infections developed DROs; these patients had higher HE (39 vs. 31%, P=0.003), hepatorenal syndrome (25 vs. 19%, P=0.006), lactulose (55 vs. 47%, P=0.008) and rifaximin use (34 vs. 27%, P=0.006) on crude comparisons but country-income distributions were similar. 29.7% were on pre-admission rifaximin, mostly HE-related; they had more advanced cirrhosis and from low/low-middle-income countries. Daptomycin was used in 1.5%, linked with DROs (5.0 vs. 1.0%, P<0.0001) without a difference in rifaximin use (1.4 vs.1.7%, P=0.61). On adjusted analysis, MELD-Na (1.03, 95% CI 1.02–1.04, P<0.001) increased, whereas male sex (0.73, 95% CI 0.58–0.92, P=0.008) and hepatitis-B (0.65, 95% CI 0.45–0.92, P=0.020) decreased DRO. Rifaximin was not associated with DROs overall (OR 1.07, 95% CI 0.80–1.43, P=0.65) or within income strata (high: 1.07, 95% CI 0.59–1.92, P=0.82, upper-middle: 1.18, 95% CI 0.74–1.85, P=0.49, low/low-middle: 1.04, 95% CI 0.60–1.81, P=0.90) despite sensitivity analyses.
Conclusions
In this large global cohort of hospitalized patients with cirrhosis and infections, 12% developed infections involving DROs. 30% had pre-admission rifaximin use which was not linked with daptomycin use or with DRO development on adjusted analysis overall or across country income groups.

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Editorial: Rifaximin and the Gut–Liver–Brain Axis—Progress and Prudence
Kevin V. Houston, Jasmohan S. Bajaj
Alimentary Pharmacology & Therapeutics.2026; 64(5): 681. CrossRef
Therapeutic drift or formulation drift: avoiding misconceptions about rifaximin and antimicrobial resistance in cirrhosis
Carmelo Scarpignato, Manuel Romero-Gómez
The Lancet Gastroenterology & Hepatology.2026; 11(9): 757. CrossRef
Therapeutic drift or formulation drift: avoiding misconceptions about rifaximin and antimicrobial resistance in cirrhosis – Authors' reply
Rajiv Jalan, Vishal C Patel, Saeed Shoaie
The Lancet Gastroenterology & Hepatology.2026; 11(9): 758. CrossRef
Hospitalisation in cirrhosis is linked to distinct gut microbiome structural and functional profiles: a multinational metagenomic study
Darja Nikitina, Ki Tae Suk, Aldo Torre, Ramazan Idilman, Mario R Alvares-da-Silva, Mette Munk Lauridsen, Andrew C Fagan, Edita Kreivenaite, Satya Priya Sharma, Elise Jonasson Nielsen, Dilara Turan, Vinay Jahagirdar, Matheus Truccolo Michalczuk, Alexander
Gut.2026; : gutjnl-2026-339378. CrossRef
Cellular Crosstalk at the Gut–Liver Interface in Liver Cirrhosis: Epithelial Barrier Failure, Bacterial Translocation and Immune Activation as a Bidirectional Network
Thomas N. Nitsotolis, Stelios F. Assimakopoulos, Eleftheria Mastoridou, Nikolaos-Gavriel Kolios, Dimitrios Biros, Eleni-Dimitra Oikonomidi, Maria Lagadinou, Alexia Papalexandrou, Haralampos Milionis, Eirini Christaki, Georgios Kalambokis
Cells.2026; 15(19): 1739. CrossRef
Gut microbial dynamics and antibiotic resistance during rifaximin therapy in severe cirrhosis: a ProPILA-Rifax ancillary study
Ruben Ladeira, Adrien Biguenet, Alexandre Meunier, Marion Gonthier, Vincent Di Martino, Anaïs Pitta, Edouard Bardou-Jacquet, Anne Jolivet-Gougeon, Maxime Desmarets, Thierry Thévenot, Didier Hocquet, Benoit Valot
Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef

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301 Download
5 Web of Science
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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
PDF

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

3,064 View
211 Download
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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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Alcohol-induced oxidative stress triggers mitochondrial Ca²⁺ release through the permeability transition pore: Kwangwoo Lee, Jiyoon Lee, Jihyo Byun, Eunmi Lee, Pilhan Kim, Won Kim, Won-Il Jeong; Clin Mol Hepatol 2026;32(2):e205-e210.
Published online March 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0005

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Interleukin-1β as target to induce synthetic lethality in KRAS mutant biliary tract cancer: Shijie Li, Yukai Shan, Tianen Chen, Win Topatana, Sarun Juengpanich, Ziyi Lu, Yuchao Sun, Tianao Xie, Ruijing Ruijing, Lidan Hou, Jiang Chen, Guojun Chen, Jiemin Lv, Xianjue Ma, Pengjuan Guo, Dan Gabriel Duda, Xiujun Cai, Mingyu Chen; Clin Mol Hepatol 2026;32(2):904-918.
Published online February 20, 2026; DOI: https://doi.org/10.3350/cmh.2025.1278

Background/Aims
Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL.
Methods
The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines.
Results
Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines.
Conclusions
In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

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Precision chemotherapy in biliary tract cancer moving from empiric intensification to biomarker-guided treatment: Editorial on “Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer”: Sung Hwan Lee, Ahmed O. Kaseb, Ju-Seog Lee; Clin Mol Hepatol 2026;32(3):1457-1460.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0179

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64 Download

Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma: Yiming Zhang, Yushan Hou, Xinxin Wang, Kaikun Xu, Pei Jiang, Siqi Wang, Huimin Kang, Hu Zhang, Jingzhuo Jin, Xiaofen Huang, Zifeng Liu, Songpeng Yang, Jiaqi Liu, Lingqiang Zhang, Fuchu He, Chunyan Tian, Aihua Sun; Clin Mol Hepatol 2026;32(2):866-883.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2025.1157

Background/Aims
Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed.
Methods
We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models.
Results
ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis.
Conclusions
ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

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circCrebrf modulates the miR-3562/ERLIN1 axis to suppress neuronal oxidative stress and apoptosis following traumatic brain injury
Wen Li, Shuhan Zhang, Boquan Shan, Jiale Gu, Fangyixiao Xu, Youming Lu, Chuanyu Cang, Jingyi Li, Xiao Han, Xiang Cheng, Yong Dai, Xinhua Zhang
Experimental Neurology.2026; 404: 115859. CrossRef
Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis
Wentao Ma, Fengxu Yan, Yu Cheng, Guoqing Zhang, Yanxi Mu, Zhiqiang Zhang, Xuefeng Liang, Jianxin Gan, Wenwei Yang, Weixiong Zhu, Yusheng Cheng
Frontiers in Immunology.2026;[Epub] CrossRef
A Nano‐Anchor for Anti‐Drift Vesicle Imaging
Yinqi Tian, Wenjing Zhu, Zhaojie Zhai, Danni Fu, Zejun Wang
Small Methods.2026;[Epub] CrossRef

2,961 View
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3 Web of Science
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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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1,594 View
47 Download

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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1,520 View
24 Download

Incorporating chronic kidney disease into the cost-effectiveness of MASLD treatment: Correspondence to letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun; Clin Mol Hepatol 2026;32(3):e415-e418.
Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0099

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Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic live
Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice
Clinical and Molecular Hepatology.2026; 32(3): e447. CrossRef

1,677 View
66 Download
1 Web of Science
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Correspondence to editorial on “Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1⁺KLRC2CD16^hi subset linked to hepatitis B virus outcomes”: Libo Tang, Yuhao Wang, Zihan Jin, Shihong Zhong, Yongyin Li; Clin Mol Hepatol 2026;32(3):e384-e386.
Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0096

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1,454 View
22 Download

Correspondence to letter to the editor on “Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1⁺KLRC2^-CD16^hi subset linked to hepatitis B virus outcomes”: Zihan Jin, Libo Tang, Yuhao Wang, Shihong Zhong, Yongyin Li; Clin Mol Hepatol 2026;32(3):e427-e429.
Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0095

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1,523 View
40 Download

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

3,267 View
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2 Web of Science
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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; Clin Mol Hepatol 2026;32(3):e419-e421.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0073

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1,205 View
18 Download

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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1,304 View
34 Download

Key challenges in cost-effectiveness analyses of emerging MASLD therapies: adherence, adverse events, cardiometabolic benefits, and age-related uncertainty: Correspondence to editorial on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun; Clin Mol Hepatol 2026;32(3):e365-e368.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0059

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CHAIN Cohort: Prospective Multicenter Study of MASLD With Serial Liver Stiffness Assessments in Cardiovascular Care
Xiao‐Dong Zhou, Ren Cheng‐Han Fan, Jian‐Dong Chen, Xi‐Qiao Zhou, Qian Tong, Yan‐Hang Gao, Xiao‐Qi Wang, Ya‐Kun Jiang, Xiang‐Yuan Pu, Yu Shi, Ming‐Wei Wang, Jing Liu, Hai‐Bing Jiang, Li Ma, Xin‐Gang Zhang, Yi‐Ling Li, Su Lin, Hong‐Ju Yang, Yao‐Hong Song, Y
Liver International.2026;[Epub] CrossRef

1,414 View
52 Download
1 Web of Science
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Correspondence to letter to the editor on “Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0”: Di Wu, Xiaojing Wang, Weiming Yan, Man-Fung Yuen, Qin Ning; Clin Mol Hepatol 2026;32(3):e408-e410.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0031

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1,406 View
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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

1,779 View
50 Download
2 Web of Science
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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

5,037 View
602 Download
1 Web of Science
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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

1,509 View
18 Download
1 Web of Science
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Extending MET-TRIB3 axis research in hepatocellular carcinoma: Immune contexture and patient subgroups: Letter to the editor on “MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation”: Lei Wu, Ning Liu, Pengyuan Song, Meili Sun; Clin Mol Hepatol 2026;32(3):e279-e282.
Published online January 14, 2026; DOI: https://doi.org/10.3350/cmh.2025.1357

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Correspondence to letter to the editor on “MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation”
Tiantian Wang, Wenjie Huang, Limin Xia
Clinical and Molecular Hepatology.2026; 32(3): e405. CrossRef
Reply to correspondence on “MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation”
Lei Wu, Yan Zheng
Clinical and Molecular Hepatology.2026; 32(3): e445. CrossRef

1,274 View
27 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

1,715 View
64 Download
2 Web of Science
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A cost-effectiveness evaluation framework for treatment for metabolic dysfunction-associated steatohepatitis: Potential and concerns: Editorial on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Sherlot Juan Song, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip; Clin Mol Hepatol 2026;32(3):1405-1408.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1459

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Key challenges in cost-effectiveness analyses of emerging MASLD therapies: adherence, adverse events, cardiometabolic benefits, and age-related uncertainty: Correspondence to editorial on “Evaluating treatment response thresholds for cost-effective treatm
Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(3): e365. CrossRef

1,349 View
45 Download
1 Web of Science
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Letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice; Clin Mol Hepatol 2026;32(3):e291-e293.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1417

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Incorporating chronic kidney disease into the cost-effectiveness of MASLD treatment: Correspondence to letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disea
Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(3): e415. CrossRef
Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic live
Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice
Clinical and Molecular Hepatology.2026; 32(3): e447. CrossRef

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27 Download
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Treatment strategies for patients with hepatitis B virus infection coexisting with hepatitis C virus or metabolic dysfunction-associated steatotic liver disease: Chieh Liu, Yi-Fen Shih, Chun-Jen Liu; Clin Mol Hepatol 2026;32(2):565-579.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1227

Abstract
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Hepatitis B virus (HBV) remains a major cause of chronic liver diseases, especially in the Asia-Pacific region. In recent decades, coinfection with hepatitis C virus (HCV) and coexistence with metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as significant clinical concerns among HBV-infected patients. Although global HBV vaccination programs and curative therapies for HCV have led to a marked decline in HBV/HCV coinfection, MASLD is rapidly becoming the predominant comorbidity due to the global surge in metabolic risk factors. HBV/HCV coinfection typically results in more severe liver damage, with unique challenges in antiviral treatment and risk of HBV reactivation post-HCV clearance. In contrast, HBV/MASLD overlap demonstrates complex metabolic-viral interactions that may influence viral replication, hepatitis B surface antigen seroclearance, fibrosis progression, and risk of hepatocellular carcinoma. This review critically compares the epidemiology, clinical outcomes, and management strategies of HBV patients with concurrent HCV or MASLD, while addressing current research gaps and proposing directions for future investigations.

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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
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0387. CrossRef

2,859 View
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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

3,383 View
156 Download
3 Web of Science
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The magic of sodium-glucose cotransporter-2 inhibitors: Benefits in metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus: Editorial on “Comparative risk of fibrosis progression with sodium-glucose cotransporter-2 vs. dipeptidyl peptidase-4 inhibitors in metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus with low-to-intermediate fibrosis”: Karen Cheuk-Ying Ho, Lung-Yi Mak; Clin Mol Hepatol 2026;32(3):1413-1416.
Published online January 6, 2026; DOI: https://doi.org/10.3350/cmh.2025.1433

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Reaffirming the role of SGLT2 inhibitors in slowing fibrotic progression in MASLD: Correspondence to editorial on “Comparative risk of fibrosis progression with sodium-glucose cotransporter-2 vs. dipeptidyl peptidase-4 inhibitors in metabolic dysfunction-
Jonggi Choi, Raymond T. Chung
Clinical and Molecular Hepatology.2026; 32(3): e369. CrossRef

1,599 View
83 Download
1 Web of Science
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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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1,396 View
60 Download

Comment on the expert consensus on treatment approaches for achieving functional cure in chronic hepatitis B: Letter to the editor on “Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0”: Seng-Gee Lim, Melanie Paff; Clin Mol Hepatol 2026;32(3):e285-e287.
Published online December 26, 2025; DOI: https://doi.org/10.3350/cmh.2025.1441

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Correspondence to letter to the editor on “Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0”
Di Wu, Xiaojing Wang, Weiming Yan, Man-Fung Yuen, Qin Ning
Clinical and Molecular Hepatology.2026; 32(3): e408. CrossRef

1,886 View
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1 Web of Science
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Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer: Daeseong Kim, Nam Suk Sim, Seonjeong Woo, Min Hwan Kim, Choong-kun Lee, Seung Soo Hong, Sung Hyun Kim, Ho Kyoung Hwang, Chang Moo Kang, Woo Jung Lee, Jung Hyun Jo, Taek Chung, Sohyun Hwang, Beodeul Kang, Jung Sun Kim, Chang-Il Kwon, Sangwoo Kim, Hong Jae Chon, Chang Gon Kim, Young Nyun Park, Hye Jin Choi; Clin Mol Hepatol 2026;32(2):721-736.
Published online December 26, 2025; DOI: https://doi.org/10.3350/cmh.2025.1019

Background/Aims
Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC.
Methods
Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy.
Results
With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (P_interaction=0.023 for PFS, P_interaction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC.
Conclusions
Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

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Systematic review and first meta-analysis of the efficacy and safety of gemcitabine-cisplatin combined with paclitaxel in patients with advanced biliary tract cancer
Gang Zhu, Shenglan Li, Yan Zhang, Guoying Feng, Guangnian Zhang, Huanli Cheng, Bo Jiang, Benjian Gao, Xiaoli Yang, Bo Li
European Journal of Clinical Pharmacology.2026;[Epub] CrossRef
CBC3T-3: a novel patient-derived cisplatin-resistant distal cholangiocarcinoma cell line harboring multiple TP53 missense mutations
Jiahui Xi, Mingzhen Bai, Ruyang Zhong, Chongfei Huang, Ruoshui An, Long Gao, Haidong Ma, Liang Tian, Jinyu Zhao, Ningzu Jiang, Xiang He, Leiqing Wang, Zihe Dong, Ping Yue, Yanyan Lin, Zhongtian Bai, Wenbo Meng
Human Cell.2026;[Epub] CrossRef
Precision chemotherapy in biliary tract cancer moving from empiric intensification to biomarker-guided treatment: Editorial on “Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer”
Sung Hwan Lee, Ahmed O. Kaseb, Ju-Seog Lee
Clinical and Molecular Hepatology.2026; 32(3): 1457. CrossRef

3,873 View
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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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1,258 View
37 Download

Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1⁺KLRC2^–CD16^hi subset linked to hepatitis B virus outcomes: Libo Tang, Yuhao Wang, Zihan Jin, Yurong Gu, Zhaofeng Zeng, Linnan Song, Xuan Yi, Lingtao Zhang, Yujing Zhang, Weiying He, Liping Wang, Weixin He, Jianru Sun, Xiaoqin Lan, Xiangyong Li, Shihong Zhong, Yongyin Li; Clin Mol Hepatol 2026;32(2):683-705.
Published online December 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0842

Background/Aims
Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment.
Methods
A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets.
Results
The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16^hiNK subpopulation (CX3CR1⁺KLRC2^–CD16^hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1⁺KLRC2^–CD16^hi subset tended to exhibit functional restoration in HBsAg-loss individuals.
Conclusions
Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1⁺KLRC2^–CD16^hiNK subset as a potential therapeutic target.

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Mechanisms and management of pegylated interferon-α toxicity in chronic hepatitis B
Liya Zhu, Fei Peng, Dingfang Pi, Jinzhi Lu
Frontiers in Immunology.2026;[Epub] CrossRef
The immunoecology of occult hepatitis B virus infection: genetic remodeling and the immune-mediated microcosm
Feng Wang, Le Wang, Zhiguo Xu, Zequn Ou, Yun Wang, Haiying Yang, Jingxian Fei, Jingxian Song, Yizhu Chen, Ke Lv
Frontiers in Immunology.2026;[Epub] CrossRef

3,007 View
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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
Cardiovascular and hepatic outcomes: prognostic differences across MASLD-MetALD-ALD continuum
Han Ah Lee, Gi-Ae Kim, Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0367. CrossRef

4,816 View
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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

1,489 View
50 Download
1 Web of Science
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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

1,416 View
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Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease: Xinrui Jin, Sherlot Juan Song, Jimmy Che-To Lai, Grace Lai-Hung Wong, Alice Pik-Shan Kong, Nana Peng, Xiang Xiao, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip; Clin Mol Hepatol 2026;32(1):353-367.
Published online December 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0860

Background/Aims
Previous studies suggest that hypothyroidism is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and its histological severity, but clinical outcome data are largely lacking. We aimed to study the impact of hypothyroidism on liver-related events (LREs).
Methods
Patients with MASLD were identified from a territory-wide registry in Hong Kong during 2000–2024. Thyroid status was determined using diagnosis codes and thyroid function tests. The primary outcome, LRE, was defined as a composite of hepatic decompensation, hepatocellular carcinoma, liver transplantation, and liver-related death.
Results
A total of 20,478 patients with MASLD were included in the final analysis (mean age 56.4±13.2 years; 43.9% male). At baseline, 18,178 (88.8%) patients were euthyroid, 598 (2.9%) were hyperthyroid, and 1,702 (8.3%) were hypothyroid. Compared with euthyroid patients, both hyperthyroidism and overt hypothyroidism were associated with cirrhosis. At a median follow-up of 4.8 years, 179 patients developed LREs, and 26 died from liver disease. Compared with patients with normal serum thyroid-stimulating hormone (TSH) levels of 0.4–4 mIU/L, those with subclinical (4–10 mIU/L; adjusted time-dependent cause-specific hazard ratio [aCSHR], 2.49; 95% CI, 1.51–4.13) and overt hypothyroidism (>10 mIU/L; aCSHR, 4.91; 95% CI, 1.56–15.47) had an increased risk of LREs. Time-dependent, but not baseline, TSH and thyroid status were associated with LRE risk.
Conclusions
Subclinical and overt hypothyroidism are associated with an increased risk of LREs in a dose-dependent manner. The association with time-dependent but not baseline thyroid status underscores the importance of thyroid monitoring and suggests that correction of hypothyroidism may mitigate LRE risk.

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Hypertension and long-term adverse clinical outcomes in MASLD: Sensitivity analyses for unmeasured or uncontrolled confounding
Guiying Gao, Xiuhong Wang, Ruizhe Huang, Jing Cao
Journal of Hepatology.2026; 84(6): e209. CrossRef
Not just fat: muscle also matters in metabolic dysfunction-associated steatotic liver disease (MASLD)
Xinyan Zong, Grace Lai-Hung Wong
Hepatology International.2026; 20(3): 550. CrossRef
Dynamic Thyroid Function Assessment May Improve Risk Prediction in Metabolic Dysfunction—Associated Steatotic Liver Disease Patients
Gabriela Brenta
Clinical Thyroidology®.2026; 38(7): 240. CrossRef
Hypothyroidism and Metabolic Dysfunction–Associated Steatotic Liver Disease: Mechanisms, Clinical Links, and Therapeutic Implications
Amjad Mahmood Qadir, Rebaz Anwar Omer
Current Obesity Reports.2026;[Epub] CrossRef

4,473 View
211 Download
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