Clinical and Molecular Hepatology

The Natural History and Individualized Prediction of Liver Stiffness–Based Fibrosis Risk in MASLD: 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 Ledinghen, Michelle Lai, Xiao-Dong Zhou, Vincent Wai-Sun Wong, Ming-Hua Zheng, On behalf of VCTE-Prognosis Study Group; Received March 4, 2026 Accepted May 10, 2026 Published online May 20, 2026; DOI: https://doi.org/10.3350/cmh.2026.0279 [Accepted]

Abstract
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Background & Aims
Liver stiffness measurement (LSM) is a key tool for risk stratification in 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).
Method
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 VCTE 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%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, 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 (DYNAMO) 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 trajectory. 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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GAFAD: An LC-MS/MS–Based Model for Early Hepatocellular Carcinoma Detection Beyond GALAD’s Limitation: Hyojin Kim, Wonseok Oh, Juri Park, Saeyoung Lee, Won Suk Yang, Soon Sun Kim, Jae Youn Cheong, Je-Hyun Baek; Received October 31, 2025 Accepted February 23, 2026 Published online February 25, 2026; DOI: https://doi.org/10.3350/cmh.2025.1244 [Accepted]

Abstract
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Background/Aims
The GALAD (Gender, Age, Lens culinaris agglutinin-reactive alpha-fetoprotein [AFP-L3], alpha-fetoprotein [AFP], and des-γ-carboxy prothrombin [DCP]) score, widely used for hepatocellular carcinoma (HCC) detection, was primarily derived from cohorts with advanced-stage tumors and elevated biomarker levels, potentially overestimating accuracy in early-stage disease. Furthemore, the lectin-based AFP-L3 assay has poor sensitivity at low AFP concentrations, limiting detection of small or AFP-negative tumors.
Methods
We developed GAFAD, a multivariable model replacing AFP-L3 with fucosylated AFP percentage (AFP-Fuc%), quantified by a validated liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay. The model was trained and tested using a hepatitis B virus (HBV)-related cohort (HCC n=235; non-HCC n=290), a diagnostically challenging set with substantial overlap in biomarker levels between HCC and non-HCC. Moreover, a final model (GAFAD) was validated in two independent cohorts (HCC n=210, non-HCC n=245), comprising HBV-, HCV-related and non-viral etiologies.
Results
In the development cohort, GAFAD showed superior diagnostic performance to GALAD for distinguishing HCC from non-HCC, with a higher area under the receiver operating characteristic curve (AUC, 0.938 vs. 0.887; p<0.0001) and greater sensitivity (82% vs. 66%) and accuracy (86% vs. 79%) at 90% specificity. In the external validation cohort, GAFAD similarly outperformed GALAD, achieving a higher AUC (0.874 vs. 0.841, p<0.05), greater sensitivity (72% vs. 57%), and improved accuracy (82% vs. 75%) at 90% specificity. This superiority extended to early-stage, very-early-stage, and AFP-negative HCC.
Conclusions
GAFAD provides a reliable and generalizable tool for early HCC detection across diverse etiologies, supporting its clinical applicability in surveillance and diagnosis.

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Aspirin on the prevention of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: Teng-Yu Lee, Chun-Ying Wu; Received January 3, 2026 Accepted January 17, 2026 Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0007 [Accepted]

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Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma: Shan Li, Jie Hu, Yihan Yan, Xinrui Liu, Xiao Dong, Huijun Liang, Xin Tang, Junji Tao, Rong Zhang, Yuan Hu, Ailong Huang, Kai Wang, Ni Tang; Clin Mol Hepatol 2026;32(2):661-682.
Published online December 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0754

Background/Aims
Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial.
Methods
A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining.
Results
Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth.
Conclusions
These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

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Integrative multi-omics profiling identifies infiltrative hepatocellular carcinoma as an immunotherapy-resistant subtype with distinct molecular features: Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon; Clin Mol Hepatol 2026;32(1):258-275.
Published online October 27, 2025; DOI: https://doi.org/10.3350/cmh.2025.0792

Background/Aims
Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).
Methods
We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.
Results
Infiltrative morphology, encompassing pure and mixed forms, was present in 42.7% of advanced HCC and associated with advanced disease features and compromised liver function. Patients with type IV infiltrative HCC showed lowest objective response rate (14.6%) and worst progression-free (median, 2.8 months) and overall survival (median, 7.1 months). Infiltrative morphology remained an independent predictor of poor outcomes after multivariable adjustment for confounders, including intrahepatic tumor extent. Genomic profiling revealed enriched TP53 and ATM loss-of-function mutations in type IV infiltrative HCC. Transcriptomic and proteomic analyses identified consistent activation of tumor proliferation, epithelial-mesenchymal transition, TGF-β signaling, and immunosuppressive pathways in type IV infiltrative HCC. Type IV infiltrative signature was significantly associated with poor survival across external datasets and retained independent prognostic value.
Conclusions
Infiltrative HCC is a clinically aggressive and molecularly distinct subtype of advanced HCC. Morphological classification and type IV infiltrative signatures may guide risk stratification and therapeutic decision-making in advanced HCC treated with immunotherapy.

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Cancers.2025; 17(24): 3967. CrossRef

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Sex‑specific trends and demographic vs. epidemiologic drivers of alcohol‑related cirrhosis in United States, 2021–2040: Letter to the editor on "Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States": Kui Wang, Yunqing Zeng; Clin Mol Hepatol 2026;32(2):e155-e157.
Published online August 25, 2025; DOI: https://doi.org/10.3350/cmh.2025.0790

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Evaluation methods of hepatic steatosis: From conventional techniques to emerging biomarkers
Kengo Moriyama
World Journal of Hepatology.2026;[Epub] CrossRef
Divergent trajectories of inflammatory bowel disease in East, South, South-East and Central Asia: A comprehensive GBD 2021 analysis
Kui Wang, Yunqing Zeng, Shanshan Zhang, Yanqing Li
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Plasma lipidomic and fungal signatures predict early mortality in acute liver failure: Yu Ji Kim, Jong-Won Kim; Clin Mol Hepatol 2026;32(1):e21-e23.
Published online August 20, 2025; DOI: https://doi.org/10.3350/cmh.2025.0813

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Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma: Sabrina Sidali, Claudia Campani, Jihyun An, Ju Hyun Shim, Jean-Charles Nault; Clin Mol Hepatol 2026;32(1):69-90.
Published online August 20, 2025; DOI: https://doi.org/10.3350/cmh.2025.0746

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major cause of cancer-related mortality worldwide. Systemic therapies, including targeted therapies and immune checkpoint inhibitors, have revolutionized the management of advanced HCC. Although the prognosis of patients with advanced HCC remains poor, significant progress has been made with recent advances in drug development, particularly with the introduction of effective treatments such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab. Indeed, treatment response varies significantly among patients, highlighting the need for robust biomarkers. In addition, the development of molecular driver-targeted therapies remains an active research focus as most genetic alterations observed in HCC are currently undruggable. Meeting these goals will require additional efforts to obtain histological material in clinical trials, in order to enable robust translational research. This review explores the current landscape of biomarkers of response to systemic treatments in HCC, including molecular, immune-based markers as well as circulating tumor DNA and highlights potential paths of improvement.

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A novel signature of palmitoylation for predicting prognosis and therapeutic response of hepatocellular carcinoma
Yun Li, Zhongquan Yi, Linhua Liu, Danping Huang
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Longjun Chen, Xiaojuan Zeng, Tianping Li
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Bing Liang, Annan Hu, Jian Zhou, Juan Li, Jian Dong
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Redefining MTCT prevention strategies toward HBV elimination: Correspondence to editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”: Moran Ki, Jong-Hyun Kim; Clin Mol Hepatol 2026;32(2):e224-e226.
Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0805

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Reply to correspondence on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Eunho Choi, Ji Hoon Kim, Young-Sun Lee
Clinical and Molecular Hepatology.2026; 32(2): e262. CrossRef

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Rethinking first-line screening in MASLD beyond the limitations of Fibrosis-4 index: Editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”: Han Ah Lee, Young Youn Cho, Hyung Joon Kim; Clin Mol Hepatol 2026;32(2):921-923.
Published online June 27, 2025; DOI: https://doi.org/10.3350/cmh.2025.0678

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

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Correspondence to letter to the editor on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
Hye Won Lee, Seung Up Kim
Clinical and Molecular Hepatology.2026; 32(2): e244. CrossRef

3,810 View
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Hydrophilic and lipophilic statin and clinical outcomes in individuals with alcohol-associated liver disease: Pojsakorn Danpanichkul, Donghee Kim, Benjamin Nah, Karn Wijarnpreecha, Suthat Liangpunsakul; Clin Mol Hepatol 2025;31(3):e273-e276.
Published online May 27, 2025; DOI: https://doi.org/10.3350/cmh.2025.0474

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Association of documented social deprivation with cardiovascular and liver outcomes in alcohol-associated liver disease
Pojsakorn Danpanichkul, Yanfang Pang, Andrew F. Ibrahim, Supapitch Sirimangklanurak, Allan Bueso, Daniel M. Simadibrata, Shu-Yen Chan, Karn Wijarnpreecha, Mazen Noureddin, Donghee Kim, Suthat Liangpunsakul
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Impact of Documented Social Vulnerability on Clinical Outcomes in Metabolic Dysfunction‐Associated Steatotic Liver Disease
Pojsakorn Danpanichkul, Yanfang Pang, Maria Inggriani, Supapitch Sirimangklanurak, Matheus Souza, Ahmad Anouti, Andrew F. Ibrahim, Nikki Duong, Thomas G. Cotter, Thomas A. Kerr, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha
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Improved survival and reduced alcohol‐associated hepatitis risk with renin‐angiotensin‐aldosterone system inhibitors in alcohol‐associated liver disease
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Liver, Cardiovascular and Infectious Outcomes in Alcohol‐Associated Liver Disease With Cardiometabolic Risk Factors
Pojsakorn Danpanichkul, Kwanjit Duangsonk, Yanfang Pang, Krittameth Rakwong, Peerapun Jit‐are‐roon, Phuuwadith Wattanachayakul, Thitiphan Srikulmontri, Benjamin Nah, Vincent L. Chen, Donghee Kim, Christos S. Mantzoros, Mazen Noureddin, Karn Wijarnpreecha
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Alcohol, Clinical and Experimental Research.2025; 49(11): 2451. CrossRef

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Correspondence to editorial on “CD36 Promotes iron accumulation and dysfunction in CD8⁺ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma”: Yifei Qin, Peng Lin, Huijie Bian, Zhi-Nan Chen, Jiao Wu; Clin Mol Hepatol 2026;32(1):e75-e78.
Published online April 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0402

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Reply to correspondence on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”: Mathias Jachs, Mattias Mandorfer; Clin Mol Hepatol 2026;32(1):e106-e108.
Published online April 16, 2025; DOI: https://doi.org/10.3350/cmh.2025.0391

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

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

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Hye Won Lee, Seung Up Kim
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Hye Won Lee, Seung Up Kim
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The MASLD Journey in the General Population: Linkage‐to‐Care and Patient‐Reported Uptake of Fibrosis Risk Assessment
Joo Hyun Oh, Jun‐Hyuk Lee, Sang Bong Ahn, Eunjoo Kwon, Eileen L. Yoon, Hyo Young Lee, Seon Cho, Dae Won Jun
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Han Ah Lee, Young Youn Cho, Hyung Joon Kim
Clinical and Molecular Hepatology.2026; 32(2): 921. CrossRef
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Methods.2025; 243: 66. CrossRef

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Emerging therapies and real-world application of metabolic dysfunction-associated steatotic liver disease treatment: Hee Yeon Kim, Mary E. Rinella; Clin Mol Hepatol 2025;31(3):753-770.
Published online April 2, 2025; DOI: https://doi.org/10.3350/cmh.2025.0083

Abstract
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Metabolic dysfunction-associated steatotic liver disease, formerly referred to as non-alcoholic fatty liver disease, is the most common liver disease in Western countries and has emerged as the leading indication for liver transplantation. Metabolic dysfunction-associated steatohepatitis (MASH), a more advanced stage, carries a high risk of progression to liver fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Until recently, lifestyle intervention remained the mainstay of MASH management, with no pharmacological treatments specifically approved. However, advances in understanding its pathophysiological mechanisms have fueled numerous clinical trials, culminating in the Food and Drug Administration’s (FDA) approval of resmetirom as the first treatment for MASH in 2024. Additionally, many investigational drugs are nearing FDA approval or progressing through late-stage clinical trials. This review examines the current therapeutic landscape, highlights strategies for identifying patients suitable for liver-directed therapies in real-world settings, and discusses the challenges that remain.

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Quzhou-sourced Fructus Aurantii ameliorates MASLD by modulating glycolysis-dependent M1 polarization in hepatic macrophages
Junbin Yan, Yunmeng Nie, Menglu Ding, Mi Zhou, Tingyuan Li, Sumei Xu, Shuo Zhang
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Karolina Kornatowska, Szymon Kopciał, Mateusz Wiekiera, Adrianna Wiekiera, Paweł Budzik, Mateusz Tyniec, Kamal Morshed
Gastroenterology Insights.2026; 17(2): 33. CrossRef
Health inequity and the risk of MAFLD/MASLD
Ziyan Pan, Abdulla Al Hassani, Khalid M. AlNaamani, Yasser Fouad, Munira Y. Altarrah, Mohammed Eslam
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Predictors of Discordance Between Controlled Attenuation Parameter and Magnetic Resonance-Proton Density Fat Fraction in Hepatic Steatosis
Dong Yun Kim, Hyung-Jin Rhee, Beom Kyung Kim
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Daniel Clayton-Chubb, William W. Kemp, Ammar Majeed, Peter W. Lange, Jessica A. Fitzpatrick, Karl Vaz, John S. Lubel, Alexander D. Hodge, Joanne Ryan, John J. McNeil, Alice J. Owen, Robyn L. Woods, Stuart K. Roberts
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Amedeo Lonardo, Ralf Weiskirchen
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Timosaponin AIII from Anemarrhena asphodeloides binds and inhibits S100A8-mediated neutrophil infiltration and NET formation ameliorates MASH
Yunfan Bai, Jingxin Ju, Ruishi Xie, Jing Li, Xinyi Zhao, Xiaoxue Fang, Ming Zhu, Xintian Lan, Haoming Luo
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From mechanisms to management: Early detection and improved treatment of MASLD and its related hepatocellular carcinoma
Dingwu Li, Xiang Zhang
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The evolution of non-invasive strategies in cirrhosis management—from screening to precision monitoring: Editorial on “Fibrosis-4plus score: a novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): an international multicenter study”: Haiyu Wang, Jinjun Chen; Clin Mol Hepatol 2026;32(1):403-406.
Published online March 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0274

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Correspondence to letter to the editor on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
Haiyu Wang, Jinjun Chen
Clinical and Molecular Hepatology.2026; 32(2): e238. CrossRef

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60 Download
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Steatotic liver disease

Addressing the burden of steatotic liver disease: The role of transient elastography: Correspondence to editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023”: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed; Clin Mol Hepatol 2025;31(2):e180-e182.
Published online February 13, 2025; DOI: https://doi.org/10.3350/cmh.2025.0125

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Fibrosis-4plus score: a novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): an international multicenter study: Bingtian Dong, Ruiling He, Shenghong Ju, Yuping Chen, Ivica Grgurevic, Jianzhong Ma, Ying Guo, Huizhen Fan, Qiang Yan, Chuan Liu, Huixiong Xu, Anita Madir, Kristian Podrug, Jia Wang, Linxue Qian, Zhengzi Geng, Shanghao Liu, Tao Ren, Guo Zhang, Kun Wang, Meiqin Su, Fei Chen, Sumei Ma, Liting Zhang, Zhaowei Tong, Yonghe Zhou, Xin Li, Fanbin He, Hui Huan, Wenjuan Wang, Yunxiao Liang, Juan Tang, Fang Ai, Tingyu Wang, Liyun Zheng, Zhongwei Zhao, Jiansong Ji, Wei Liu, Jiaojiao Xu, Bo Liu, Xuemei Wang, Yao Zhang, Qiong Yan, Hui Liu, Xiaomei Chen, Shuhua Zhang, Yihua Wang, Yang Liu, Li Yin, Yanni Liu, Yanqing Huang, Li Bian, Ping An, Xin Zhang, Shaoting Zhang, Jinhua Shao, Xiangman Zhang, Wei Rao, Chaoxue Zhang, Christoph Frank Dietrich, Won Kim, Xiaolong Qi; Clin Mol Hepatol 2025;31(3):881-898.
Published online February 5, 2025; DOI: https://doi.org/10.3350/cmh.2024.0898

Background/Aims
A large percentage of patients undergoing esophagogastroduodenoscopy (EGD) screening do not have esophageal varices (EV) or have only small EV. We evaluated a large, international, multicenter cohort to develop a novel score, termed FIB-4plus, by combining the fibrosis-4 (FIB-4) score, liver stiffness measurement (LSM), and spleen stiffness measurement (SSM) to identify high-risk EV (HRV) in compensated cirrhosis.
Methods
This international cohort study involved patients with compensated cirrhosis from 17 Chinese hospitals and one Croatian institution (NCT04546360). Two-dimensional shear wave elastography-derived LSM and SSM values, and components of the FIB-4 score (i.e., age, aspartate aminotransferase, alanine aminotransferase, and platelet count [PLT]) were combined using machine learning algorithms (logistic regression [LR] and extreme gradient boosting [XGBoost]) to develop the LR-FIB-4plus and XGBoost-FIB-4plus models, respectively. Shapley Additive exPlanations method was used to interpret the model predictions.
Results
We analyzed data from 502 patients with compensated cirrhosis who underwent EGD screening. The XGBoost-FIB-4plus score demonstrated superior predictive performance for HRV, with an area under the receiver operating characteristic curve (AUROC) of 0.927 (95% confidence interval [CI] 0.897–0.957) in the training cohort (n=268), and 0.919 (95% CI 0.843–0.995) and 0.902 (95% CI 0.820–0.984) in the first (n=118) and second (n=82) external validation cohorts, respectively. Additionally, the XGBoost-FIB-4plus score exhibited high AUROC values for predicting EV across all cohorts. The FIB-4plus score outperformed the individual parameters (LSM, SSM, PLT, and FIB-4).
Conclusions
The FIB-4plus score effectively predicted EV and HRV in patients with compensated cirrhosis, providing clinicians with a valuable tool for optimizing patient management and outcomes.

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The evolution of non-invasive strategies in cirrhosis management—from screening to precision monitoring: Editorial on “Fibrosis-4plus score: a novel machine learning-based tool for screening high-risk varices in compensated cirrhosis (CHESS2004): an inter
Haiyu Wang, Jinjun Chen
Clinical and Molecular Hepatology.2026; 32(1): 403. CrossRef
Metabolic factor-based machine learning model for mortality prediction in acute hepatitis E: Development and validation from a dual-center cohort
Haoshuang Fu, Shuying Song, Yuelin Xiao, Bingying Du, Gangde Zhao, Tianhui Zhou, Yanan Du
Digestive and Liver Disease.2026; 58(5): 660. CrossRef
Relative change rate of liver stiffness measurements predicts the risk of liver decompensation in compensated advanced chronic liver disease
Yanqiu Li, Zihang Qiao, Jinze Li, Bingbing Zhu, Yu Lu, Ying Feng, Xianbo Wang
Clinical and Experimental Medicine.2025;[Epub] CrossRef
Artificial Intelligence Applications in the Diagnosis and Management of Cirrhosis and Portal Hypertension: A Narrative Review
Amrit Khooblall, Satish E. Viswanath, Layth Khawaja, Sameer Gadani
Techniques in Vascular and Interventional Radiology.2025; 28(4): 101078. CrossRef
Liver stiffness measurement-based risk score for predicting liver decompensation risk: a single-center retrospective Chinese study
Yanqiu Li, Zihang Qiao, Jinze Li, Yongqi Li, Ying Feng, Xianbo Wang
Clinical and Experimental Medicine.2025;[Epub] CrossRef
Metabolomics and metabolites in cancer diagnosis and treatment
Minyi Cai, Haiyan Liu, Chen Shao, Tingting Li, Jun Jin, Yahui Liang, Jinhu Wang, Ji Cao, Bo Yang, Qiaojun He, Xuejing Shao, Meidan Ying
Molecular Biomedicine.2025;[Epub] CrossRef

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Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis: Jae Yeon Kim, Hyeri Park, Soo Young Park, Se Ho Kim, Ja Yun Lim, Ki Seog Lee, Si Hyun Bae, Gi Jin Kim; Clin Mol Hepatol 2025;31(3):823-840.
Published online January 22, 2025; DOI: https://doi.org/10.3350/cmh.2024.0741

Background/Aims
Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration.
Methods
We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCs^PRL-1) in a bile duct ligationinduced rat injury model, focusing on their ability to regulate EMT.
Results
PD-MSCs^PRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs. The transplantation of PD-MSCs^PRL-1 enhanced BMP7/SMAD1/5 expression, promoting epithelial marker expression and stimulating BMP7 within hepatocytes, modulating downstream SMAD signaling. Importantly, further validation confirmed that PRL-1 directly interacts with BMP7 in hepatocytes.
Conclusions
PRL-1 expression in PD-MSCs^PRL-1 restores TGFB1/BMP7 balance, promoting hepatic regeneration through mesenchymal-to-epithelial transition. These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.

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Modulation of PRL-1 in placental MSCs: A novel therapeutic strategy for hepatic fibrosis: Editorial on “Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal t
Lihai Jiang, Wenjie Zheng
Clinical and Molecular Hepatology.2026; 32(1): 377. CrossRef
3D-cultured hUC-MSC-derived exosomes as macrophage mediators to suppress cholestatic fibrosis in mice via miR-1291–mediated multi-targeted pathways
Yu Liu, Senyi Gong, Xingyu Luo, Yuwen Hu, Qinbiao Yan, Zhe Yang, Ali Mohsin, Shusen Zheng, Meijin Guo
Chemical Engineering Journal.2026; 532: 174376. CrossRef
Advances in Biliary Disease Organoid Research: From Model Construction to Clinical Applications
Boming Peng, Min Huang, Jianquan Zhang, Yang Xiang
Advanced Healthcare Materials.2025;[Epub] CrossRef
Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells
Xuan Pan, Tianyun Gao, Bin Wang
Cell & Bioscience.2025;[Epub] CrossRef

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Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial: Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Woong Lee, Jung Hyun Kwon, Moon Young Kim, Do Seon Song, Jung Gil Park, Yoon Seok Lee, Eileen L. Yoon, Han Ah Lee, Seong Hee Kang, Jin Mo Yang; Clin Mol Hepatol 2025;31(3):810-822.
Published online January 17, 2025; DOI: https://doi.org/10.3350/cmh.2024.0819

Background/Aims
Besifovir (BSV) showed comparable antiviral activity and superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment.
Methods
In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks.
Results
The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% confidence interval –0.01 to 0.04; P>0.999), with a predefined margin of –0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (–1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group.
Conclusions
In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF.

Citations

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Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef
Besifovir: a viable option for long-term disease control in chronic hepatitis B: Editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Wai-Kay Seto
Clinical and Molecular Hepatology.2026; 32(1): 374. CrossRef
Tenofovir amibufenamide in chronic hepatitis B: Lipid changes and 144-week safety with tenofovir disoproxil fumarate-to-tenofovir amibufenamide switch
Zhi-Hao Zeng, Jin-Qing Liu, Min Zhang, Cai-Liang Qiu, Zhen-Yu Xu
World Journal of Gastroenterology.2025;[Epub] CrossRef

12,384 View
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Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure: Neha Sharma, Sushmita Pandey, Gaurav Tripathi, Manisha Yadav, Nupur Sharma, Babu Mathew, Abhishak Gupta, Vasundhra Bindal, Sadam H. Bhat, Yash Magar, Rimsha Saif, Sanju Yadav, Amritpal Kaur, Rakhi Maiwall, Shvetank Sharma, Shiv Kumar Sarin, Jaswinder Singh Maras; Clin Mol Hepatol 2025;31(4):1233-1251.
Published online December 13, 2024; DOI: https://doi.org/10.3350/cmh.2024.0554

Background/Aims
Acute liver failure (ALF) has high mortality predominantly due to compromised immune system and increased vulnerability to bacterial and fungal infections.
Methods
Plasma lipidome and fungal peptide-based community (mycobiome) analysis were performed in discovery cohort (ALF=40, healthy=5) and validated in a validation cohort of 230 patients with ALF using high-resolution-mass-spectrometry, artificial neural network (ANN) and machine learning (ML).
Results
Untargeted lipidomics identified 2,013 lipids across 8 lipid group. 5 lipid-species—phosphatidylcholine (PC)[15:0/17:0], PC[20:1/14:1], PC[26:4/10:0], PC[32:0] and TG[4:0/10:0/23:6]—significantly differentiated ALF-NS (FC>10, P<0.05, FDR<0.01). Mycobiome alpha/beta diversity was significantly higher and showed 4 phyla and >20 species significantly dysregulated in ALF-NS linked with lipid metabolism, fatty acid elongation in ER, and others (P<0.05). Lipid and mycobiome diversity values in ALF-NS were strongly correlated (r²>0.7, P<0.05). Multi-modular correlation network showed striking associations between lipid, fungal peptide modules, and clinical parameters specific to ALF-NS (P<0.05). Cryptococcus amylolentus CBS6039 and Penicillium oxalicum 1142 directly correlated with phosphatidylcholine, triglycerides, and severity in ALF-NS (r²>0.85, P<0.05). POD-fungus and POD-lipids showed direct association with infection, necrosis, and hepatic encephalopathy (Beta>1.2, P<0.05). POD-lipid (AUC=0.969 and HR=1.99 [1.02–2.04]) superseded POD-fungus and severity indices for early-mortality prediction. Finally, significant increase in PC (15:0/17:0) level showed highest normalized importance, and ANNs and ML predicted early mortality with >95% accuracy, sensitivity, and specificity. Interestingly, fungal surveillance protein Clec7a was significantly downregulated (>2-fold), leading to a notable increase in fungal infection-mediated choline/phosphatidylcholine and associated enzymes (FC>1.5; Kennedy cycle). This contributed to phosphatidic acid-mediated hyper-inflammation in ALF-NS.
Conclusions
In ALF, the plasma lipidome and mycobiome are dysregulated. Increased circulating phosphatidylcholine could stratify ALF predisposed to early mortality or require emergency liver transplantation.

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Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management
S. K. Sarin, Ashok Choudhury, Anupam Kumar, Nadim Mahmud, G. H. Lee, Qin Ning, Soek-Siam Tan, Kessarin Thanapirom, Vinod Arora, Nobuaki Nakayama, Jun Li, Constantine J. Karvellas
Nature Reviews Gastroenterology & Hepatology.2026; 23(5): 411. CrossRef
Plasma lipidomic and fungal signatures predict early mortality in acute liver failure
Yu Ji Kim, Jong-Won Kim
Clinical and Molecular Hepatology.2026; 32(1): e21. CrossRef
Lipidomic profiles associated with treatment related hepatotoxicity in children with acute lymphoblastic leukemia
Emily J. Mason, Jeremy M. Schraw, John P. Woodhouse, M. Monica Gramatges, Kevin J. Williams, Baojiang Chen, Melissa B. Harrell, Olga A. Taylor, Michael E. Scheurer, Philip J. Lupo, Karen R. Rabin, Joanna S. Yi, Van Huynh, Steven D. Mittelman, Etan Orgel,
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Mycology.2026;[Epub] CrossRef
Distinct bile mycobiome signature identifies fungal peptide panel predictive for gallbladder carcinoma
Sanju Yadav, Nupur Sharma, Manisha Yadav, Neha Sharma, Gaurav Tripathi, Sadam H. Bhat, Sushmita Pandey, Babu Mathew, Vasundhra Bindal, Rimsha Saifi, Vipul Sharma, Sanyam Falari, Viniyendra Pamecha, Jaswinder Singh Maras
Molecular Therapy Oncology.2026; 34(2): 201220. CrossRef

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Viral hepatitis

Reply to correspondence on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”: Mirko Zoncapè, Emmanuel A. Tsochatzis; Clin Mol Hepatol 2025;31(1):e117-e118.
Published online November 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0994

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Liver fibrosis, cirrhosis, and portal hypertension

Stem cell exosomes: new hope and future potential for relieving liver fibrosis: Lihua Li, Yongjie Liu, Kunpeng Wang, Jinggang Mo, Zhiyong Weng, Hao Jiang, Chong Jin; Clin Mol Hepatol 2025;31(2):333-349.
Published online November 7, 2024; DOI: https://doi.org/10.3350/cmh.2024.0854

Abstract
PDF

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

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Lihai Jiang, Wenjie Zheng
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Yunbo Xie, Ziying Zhang, Yuefei Pan, Fu-Sheng Wang
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Acta Biomaterialia.2025; 205: 81. CrossRef
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Journal of Biochemical and Molecular Toxicology.2025;[Epub] CrossRef
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Liver fibrosis, cirrhosis, and portal hypertension

Modulation of lymphatic vessels in management of liver disease and complications: Aarti Sharma, Pinky Juneja, Shiv K Sarin, Savneet Kaur; Clin Mol Hepatol 2025;31(2):665-668.
Published online October 17, 2024; DOI: https://doi.org/10.3350/cmh.2024.0793

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The interplay between lymphatic system and portal hypertension: a comprehensive review
Pinky Juneja, Rajni Yadav, Dinesh M. Tripathi, Savneet Kaur
Hepatology International.2025; 19(4): 720. CrossRef

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Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on “Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis”: Young Eun Chon, Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2025;31(1):e61-e63.
Published online October 15, 2024; DOI: https://doi.org/10.3350/cmh.2024.0878

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Advances in Diagnostic and Therapeutic Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease
Ryan Njeim, Omar Abureesh, Ali Sohail, Ryan Tam, Liliane Deeb
Livers.2026; 6(3): 35. CrossRef

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Steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments: Carlos Jose Pirola, Maria Silvina Landa, Mariano Schuman, Silvia Inés García, Adrian Salatino, Silvia Sookoian; Clin Mol Hepatol 2025;31(1):179-195.
Published online October 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0359

Background/Aims
Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis.
Methods
Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis.
Results
There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts.
Conclusions
This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.

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Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial: Woo Hyun Paik, Joo Kyung Park, Moon Jae Chung, Gunn Huh, Ce Hwan Park, Sang Hyub Lee, Heon Se Jeong, Hee Jin Kim, Do Hyun Park; Clin Mol Hepatol 2025;31(1):119-130.
Published online September 24, 2024; DOI: https://doi.org/10.3350/cmh.2024.0629

Background/Aims
A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC.
Methods
In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events.
Results
The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated.
Conclusions
HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

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Published online September 20, 2024; DOI: https://doi.org/10.3350/cmh.2024.0766

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PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”: Baokai Sun, Likun Zhuang; Clin Mol Hepatol 2025;31(1):e67-e69.
Published online September 10, 2024; DOI: https://doi.org/10.3350/cmh.2024.0744

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Autoimmune liver disease

Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis: Jihyun An, Young Eun Chon, Gunho Kim, Mi Na Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Miyoung Choi, Dae Won Jun, Seung Up Kim, Ji Won Han, Young-Joo Jin; Clin Mol Hepatol 2024;30(Suppl):S134-S146.
Published online August 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0586

Background/Aims
The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease.
Methods
Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, according to liver biopsy.
Results
Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87, 0.89, and 0.99 for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88, 0.88, and 0.92, respectively, while in PSC, they were 0.88, 0.95, and 0.92, respectively. The cutoff values for AF were 7.5–17.9 kPa in PBC, 8.18–12.1 kPa in AIH, and 9.6 kPa in PSC.
Conclusions
VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases. This non-invasive method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

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Steatotic liver disease

Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis: Young Eun Chon, Young-Joo Jin, Jihyun An, Hee Yeon Kim, Miyoung Choi, Dae Won Jun, Mi Na Kim, Ji Won Han, Han Ah Lee, Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2024;30(Suppl):S117-S133.
Published online August 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0392

Background/aims
Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF.
Methods
Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated.
Results
A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80–0.86), 0.83 (0.80–0.86), 0.87 (0.84–0.90), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86–0.92), 0.92 (0.89–0.94), 0.89 (0.86–0.92), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1–7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62–3.8 kPa.
Conclusions
VCTE (7.1–7.9 kPa) and MRE (3.62–3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

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Suebin Park, Su-Hyeon Lee, Se-eun Han, Beom Kyung Kim, Byungjin Hwang
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Lean Metabolic Dysfunction‐Associated Steatotic Liver Disease: A Wolf in Sheep's Clothing
Xixi Fang, Chenhao Xu, Jun Lu, Runzhou Zhuang, Xiao Xu, Xuyong Wei
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Mistakes in the utilization of vibration-controlled transient elastography in the evaluation of liver fibrosis: a narrative review
Madunil Anuk Niriella, Uditha Bandara Dassanayake, Charith Priyanga Madurapperuma, Indeewari Prathibha Wijesingha, Arjuna Priyadarshin De Silva, Hithnadura Janaka de Silva
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Transient Elastography and Fibroscan: Stethoscope of a Hepatologist in Today’s World
Sajid Jalil, Mangesh Pagadala, Nicholas Dunn, Hanna Blaney, Mohamed Elfeki, Nimish Thakral, Ashwani K. Singal
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Comparative analysis of non-invasive fibrosis markers: Insights from chronic HBV, HBV+HDV, and HCV infections
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Infectious Medicine.2025; 4(4): 100220. CrossRef

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Hepatic neoplasm

Assessment of the postoperative prognosis in patients with hepatocellular carcinoma using vibration-controlled transient elastography: A systemic review and meta-analysis: Jung Hwan Yu, Ji Won Han, Young Ju Suh, Young Eun Chon, Hee Yeon Kim, Ji Hyun An, Young-Joo Jin, Miyoung Choi, Seung Up Kim, Dae Won Jun, Han Ah Lee, Mi Na Kim; Clin Mol Hepatol 2024;30(Suppl):S186-S198.
Published online August 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0366

Backgrounds/Aims
This meta-analysis examined whether preoperative vibration-controlled transient elastography (VCTE) can predict postoperative complications and recurrence in patients undergoing hepatic resection for hepatocellular carcinoma (HCC).
Methods
A systematic literature search was conducted using Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases. Out of 431 individual studies, thirteen published between 2008 and 2022 were included. Five studies focused on HCC recurrence, while eight examined postoperative complications.
Results
The meta-analysis of five studies on HCC recurrence showed that the high-risk group with a high VCTE score had a significantly increased recurrence rate after hepatic resection (hazard ratio 2.14). The cutoff value of VCTE in the high-risk group of HCC recurrence was 7.4–13.4 kPa, the sensitivity was 0.60 (95% confidence interval [CI] 0.47–0.72), and the specificity was 0.60 (95% CI 0.46–0.72). The area under the receiver operating characteristic curve (AUC) of the liver stiffness measured by VCTE to predict the HCC recurrence was 0.63 (95% CI 0.59–0.67). The meta-analysis on the postoperative complications revealed a significantly increased risk of postoperative complications in the high-risk group (12–25.6 kPa) with a high VCTE value (odds ratio [OR], 8.32). The AUC of the liver stiffness measured by VCTE to predict the postoperative complications was 0.87 (95% CI 0.84–0.90), the sensitivity was 0.76 (95% CI 0.55–0.89) and the specificity was 0.85 (95% CI 0.73–0.92).
Conclusions
This meta-analysis suggests that preoperative VCTE in patients undergoing hepatic resection for HCC is useful in identifying individuals at a high risk of postoperative complications and HCC recurrence.

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Comparison of patients with HCC with and without MASLD after surgical resection
Chia-Jung Ho, Hao-Jan Lei, Chun-Ting Ho, Gar-Yang Chau, Shu-Cheng Chou, Elise Chia-Hui Tan, Pei-Chang Lee, Yi-Hsiang Huang, Ying-Ying Yang, Teh-Ia Huo, Ming-Chih Hou, Jaw-Ching Wu, Chien-Wei Su
JHEP Reports.2026; 8(4): 101768. CrossRef
Liver Stiffness Measured by Vibration-Controlled Transient Elastography Predicts Hepatic Decompensation in Patients with Hepatocellular Carcinoma Receiving Systemic Treatments
Jaejun Lee, Hyun Yang, Si Hyun Bae, Hee Sun Cho, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Keungmo Yang, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, Do Seon Song, Seok Hwan Kim, Myung Jun Song, Soon Kyu Lee, Jung H
Liver Cancer.2026; : 1. CrossRef
Recent Trends in Noninvasive Tests for Assessing Hepatic Fibrosis in Patients with Chronic Liver Disease
Jung Hwan Yu
The Korean Journal of Medicine.2024; 99(5): 232. CrossRef

7,020 View
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4 Web of Science
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Liver fibrosis, cirrhosis, and portal hypertension

From invasive to intuitive: The emerging role of non-invasive models in hepatic decompensation: Editorial on “Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)”: Akhil Deshmukh, Rakhi Maiwall; Clin Mol Hepatol 2025;31(2):577-580.
Published online August 19, 2024; DOI: https://doi.org/10.3350/cmh.2024.0661

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Correspondence to editorial on “Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)”
Chuan Liu, Ling Yang, Hong You, Gao-Jun Teng, Xiaolong Qi
Clinical and Molecular Hepatology.2025; 31(2): e155. CrossRef

8,784 View
57 Download
1 Web of Science
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Hepatic neoplasm

Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-analysis: Han Ah Lee, Mi Na Kim, Hye Ah Lee, Miyoung Choi, Jung Hwan Yu, Young-Joo Jin, Hee Yeon Kim, Ji Won Han, Seung Up Kim, Jihyun An, Young Eun Chon; Clin Mol Hepatol 2024;30(Suppl):S172-S185.
Published online August 12, 2024; DOI: https://doi.org/10.3350/cmh.2024.0262

Backgrounds/Aims
Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of vibration-controlled transient elastography (VCTE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR.
Methods
We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies’ methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models.
Results
We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine VCTE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment VCTE >9.2–13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. VCTE >8.4–11 kPa and FIB-4 >3.25 measured after SVR maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment VCTE. That of VCTE measured after the SVR was 11.2 kPa.
Conclusions
VCTE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Citations

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2025 KASL clinical practice guidelines for management of hepatitis C
Eun Sun Jang, Nae Yun Heo, Jae Yoon Jeong, Jung Gil Park, Do Seon Song, Eun Ju Cho, Chang Hun Lee, Jae Seung Lee, Jae Hyun Yoon, Seul Ki Han, Young Kul Jung
Clinical and Molecular Hepatology.2026; 32(1): 1. CrossRef
Editorial: Residual HCC Risk After Hepatitis C Cure—Can Polygenic Risk Scores Refine Surveillance?
Heechul Nam, Sung Won Lee
Alimentary Pharmacology & Therapeutics.2026; 63(10): 1427. CrossRef
Comment: Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus
Xinpu Miao, Haidong Wu, Jinrong Xu, Wei Cheng
Clinical and Molecular Hepatology.2025; 31(1): e23. CrossRef
Hepatocellular carcinoma surveillance after sustained virological response in chronic hepatitis C: Editorial on “Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-ana
Ho Soo Chun, Minjong Lee
Clinical and Molecular Hepatology.2025; 31(1): 261. CrossRef
Longitudinal Effects of Glecaprevir/Pibrentasvir on Liver Function, Fibrosis, and Hepatocellular Carcinoma Risk in Chronic Hepatitis C: A Prospective Multicenter Cohort Study
Jung Hee Kim, Jae Hyun Yoon, Sung-Eun Kim, Ji-Won Park, Yewan Park, Gi-Ae Kim, Seong Kyun Na, Young-Sun Lee, Jeong Han Kim
Medicina.2025; 61(9): 1601. CrossRef
Precision Strategy for Hepatocellular Carcinoma Surveillance after Hepatitis C Cure: Debates across Guidelines
Masaaki Mino, Eiji Kakazu, Tatsuya Kanto
Gut and Liver.2025; 19(5): 651. CrossRef
Liver Stiffness Measurements After Oral Antivirals Effectively Predict the Risk of HCC in Patients With Chronic Hepatitis C
Yu Rim Lee, Hyun Young Woo, Young Oh. Kweon, Won Young Tak, Se Young Jang, Jung Gil Park, Min Kyu Kang, Jeong Eun Song, Byoung Kuk Jang, Changhyeong Lee, Byung Seok Kim, Jae Seok Hwang, Woo Jin Chung, Jeong Heo, Nae‐Yun Heo, Seung Ha Park, Jun Sik Yoon, J
Journal of Gastroenterology and Hepatology.2025; 40(10): 2568. CrossRef
Diagnostic possibilities of perfusion computed tomography in assessing fibrosis regression in patients with chronic viral hepatitis C: a prospective study
E. A. Ioppa, O. S. Tonkikh, I. Yu. Degtyarev, V. D. Zavadovskaya, E. S. Garganeeva
Diagnostic radiology and radiotherapy.2025; 16(3): 65. CrossRef
Liver Fibrosis Assessment in Chronic Liver Diseases Using Elastography: A Comprehensive Review of Vibration-Controlled Transient Elastography and Shear Wave Elastography
Han Ah Lee
Clinical Ultrasound.2024; 9(2): 70. CrossRef

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Steatotic liver disease

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD: Baokai Sun, Xiaoqian Ding, Jie Tan, Jie Zhang, Xueru Chu, Shuimi Zhang, Shousheng Liu, Zhenzhen Zhao, Shiying Xuan, Yongning Xin, Likun Zhuang; Clin Mol Hepatol 2024;30(4):863-882.
Published online July 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.0268

Backgrounds/Aims
Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
Methods
The Tm6sf2^167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2^167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC).
Results
The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2^167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice.
Conclusions
The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

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Rong Yang, Can Shen, Yu Jia, Yi Yao, Yiheng Zhou, Yu Cheng, Yonglang Cheng, Rui Zeng, Zhi Wan, Qian Zhao, Dongze Li, Xiaoyang Liao
Clinical and Translational Gastroenterology.2026; 17(1): e00949. CrossRef
High-protein diets and metabolic dysfunction-associated steatotic liver disease: A double-edged sword in liver health
Hong-Yuan Yin, Qian-Hui You, Wei-Jie Zhang, Guang Ji, Yan-Qi Dang
World Journal of Gastroenterology.2026;[Epub] CrossRef
Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models
Jack Leslie, Kishore A. Krishnamurthy, Indresh K. Gopalsamy, Patricia Inacio, Meritxell Huch, Suchira Gallage, Fiona Oakley, Michele Vacca
Nature Reviews Gastroenterology & Hepatology.2026; 23(4): 286. CrossRef
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Tianyang Jin, Yanni Zhao, Tingxin Xu, Yi Fang, Yaqian Cui, Wenqi Liu, Yongqiang Xiong, Jiaxi Ye, Wu Luo, Bo Hong, Guang Liang, Xiang Hu, Lijiang Huang, Yi Wang
International Immunopharmacology.2026; 174: 116351. CrossRef
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Masashi Hirooka, Teruki Miyake, Ryo Yano, Yoshiko Nakamura, Yuki Okazaki, Toyoki Shimamoto, Atsushi Yukimoto, Yasunori Yamamoto, Takao Watanabe, Osamu Yoshida, Kana Hirooka, Yoshio Tokumoto, Masanori Abe, Takeru Iwata, Yoichi Hiasa
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Gang Zhou, Xihan Gu, Xinyao Zhou, Shuai Chen, Hanyang Liu, Jing Wang
BMJ Open Gastroenterology.2026; 13(1): e002123. CrossRef
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Bojia Li, Shengai Piao, Yin Fu, Qiang Fu, Peiyao Qin, Weitai Kong, Yidi Ma, Zhe Zhang, Xue Fang, Xiaoyang Hu
Frontiers in Endocrinology.2026;[Epub] CrossRef
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Shuo Zhou, Daya Zhang, Runyu Chen, Yan-ting Lv, Da Li, Xianfeng Huang, Fengjiao Mao, Shimei Huang, Shiju Chen, Chen Chen, Ying Mo, Yiping Du, Yuliang Huang, Fan Zeng, Qicen Yao, Feihu Bai
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Zilong Wu, Xinyi Chen, Xiaoying Pan, Kai Luo, Zixiong Zhang, Changyu Zhou, Haibo Wang, Chuying Huang
Frontiers in Bioscience-Landmark.2026;[Epub] CrossRef
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Aleksandra Klisic, Ratko Tomašević, Slavko Djuraskovic, Filiz Mercantepe, Ana Ninic
Archives of Medical Science.2026;[Epub] CrossRef
PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
Baokai Sun, Likun Zhuang
Clinical and Molecular Hepatology.2025; 31(1): e67. CrossRef
TM6SF2 and PNPLA3: A potential dynamic duo?: Editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
Andrea Caddeo, Rosellina M. Mancina
Clinical and Molecular Hepatology.2025; 31(1): 293. CrossRef
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Chao Zhang, Tao Yang, Yuan Yu, Qian Jia, Wan-Meng Xiao, Sha Liu, Ze-Hui Yu, Cheng-Li Wen, Yan Wei, Hao Li, Mu-Han Lü
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Mohammad Shafi Kuchay, Narendra Singh Choudhary, Bruno Ramos-Molina
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Shuichiro Shiina, Javkhlan Maikhuu, Qing Deng, Terguunbileg Batsaikhan, Lariza Marie Canseco, Maki Tobari, Hitoshi Maruyama, Hiroaki Nagamatsu, Diana Alcantara-Payawal, Rino Gani, Yi-Hsiang Huang, Tawesak Tanwandee, Giovanni Galati, Yoon Jun Kim
Clinical and Molecular Hepatology.2025; 31(3): 671. CrossRef

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18 Web of Science
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Hepatic neoplasm

UBE2S: A novel driver of HIF-1alpha-induced metabolic reprogramming in hepatocellular carcinoma: Editorial on “UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL”: Martina Mang Leng Lei, Terence Kin Wah Lee; Clin Mol Hepatol 2025;31(1):281-285.
Published online July 23, 2024; DOI: https://doi.org/10.3350/cmh.2024.0568

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Reply to correspondence on “UBE2S: A novel driver of HIF-1alpha-induced metabolic reprogramming in hepatocellular carcinoma”
Martina Mang Leng Lei, Terence Kin Wah Lee
Clinical and Molecular Hepatology.2025; 31(1): e119. CrossRef
Correspondence to editorial on “UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL”
Renyu Zhang, Ding Wei, Zhinan Chen, Huijie Bian
Clinical and Molecular Hepatology.2025; 31(1): e58. CrossRef

6,548 View
97 Download
2 Web of Science
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Viral hepatitis

Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis: Mi Na Kim, Jihyun An, Eun Hwa Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Young-Joo Jin, Young Eun Chon, Seung Up Kim, Dae Won Jun, Ji Won Han, Miyoung Choi; Clin Mol Hepatol 2024;30(Suppl):S106-S116.
Published online July 23, 2024; DOI: https://doi.org/10.3350/cmh.2024.0371

Backgrounds/Aims
Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN).
Methods
The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis.
Results
Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66–0.86) and 0.72 (95% CI, 0.60–0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72–0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50–0.76) and specificity of 0.83 (95% CI, 0.72–0.90).
Conclusions
Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Citations

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Chronic Hepatitis B Infection: Patient Guidance
Lung‐Yi Mak, Jimmy Che‐To Lai, Ken Liu, Rashid Lui, Sakkarin Chirapongsathorn, Kuo Chao Yew, Mara Teresa Panlilio, Cosmas Rinaldi Adithya Lesmana, Ruveena Bhavani Rajaram, Liang Shen, Desmond Cheung, Lung‐Fai Wong, Hye Won Lee, Madhumita Premkumar, Anand
Journal of Gastroenterology and Hepatology.2026; 41(1): 61. CrossRef
Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study
Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
Health Science Reports.2025;[Epub] CrossRef
Head‐to‐Head Comparison of Long‐Term HCC Risk of Antivirals‐Treated Versus Untreated Low‐Level Viremia in HBV‐Compensated Cirrhosis
Nobuharu Tamaki, Daniel Q. Huang, Hyung Woong Lee, Soo Young Park, Yu Rim Lee, Dong Hyun Sinn, Tae Seop Lim, Hiroyuki Marusawa, Seng Gee Lim, Hironori Ochi, Masahiko Kondo, Yasushi Uchida, Haruhiko Kobashi, Koichiro Furuta, Masayuki Kurosaki, Beom Kyung K
Journal of Gastroenterology and Hepatology.2025; 40(6): 1595. CrossRef
Assessing Liver Fibrosis in Chronic Hepatitis B: Liver Biopsy or Non-Invasive Fibrosis Markers?
Deniz Borcak, Zuhal Yesilbag, Yusuf Emre Ozdemir, Adile Sevde Demir, Esra Salim Dogdas, Aysegul Inci Sezen, Esra Canbolat Unlu, Sevtap Senoglu, Hayat Kumbasar Karaosmanoglu, Kadriye Kart Yasar
Journal of Clinical Medicine.2025; 14(22): 8164. CrossRef
Vibration-Controlled Transient Elastography in Chronic Liver Disease: Current Research Insights
Ho Soo Chun
Clinical Ultrasound.2025; 10(2): 69. CrossRef
Recent Trends in Noninvasive Tests for Assessing Hepatic Fibrosis in Patients with Chronic Liver Disease
Jung Hwan Yu
The Korean Journal of Medicine.2024; 99(5): 232. CrossRef
Noninvasive Imaging Test to Assess Liver Fibrosis: Vibration-controlled Transient Elastography
Mi Na Kim
The Korean Journal of Gastroenterology.2024; 84(5): 201. CrossRef
Liver Fibrosis Assessment in Chronic Liver Diseases Using Elastography: A Comprehensive Review of Vibration-Controlled Transient Elastography and Shear Wave Elastography
Han Ah Lee
Clinical Ultrasound.2024; 9(2): 70. CrossRef

7,180 View
140 Download
6 Web of Science
Crossref

Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis: Young-Joo Jin, Hee Yeon Kim, Young Ju Suh, Chae Hyeon Lee, Jung Hwan Yu, Mi Na Kim, Ji Won Han, Han Ah Lee, Jihyun An, Young Eun Chon, Dae Won Jun, Miyoung Choi, Seung Up Kim; Clin Mol Hepatol 2024;30(Suppl):S159-S171.
Published online July 23, 2024; DOI: https://doi.org/10.3350/cmh.2024.0163

Backgrounds/Aims
Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using VCTE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients.
Methods
A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used VCTE were finally registered. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were considered summary estimates of treatment effect sizes of ≥11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model.
Results
Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45–4.54) in CHB patients with a baseline LSM of ≥11 kPa compared to patients who did not. In ten studies included, LSM of ≥11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50–71%) and 78% (95% CI, 66–86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70–0.77).
Conclusions
The risk of HCC development was elevated in CHB patients with VCTE-determined LSM of ≥11 kPa. This finding suggests that VCTE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Citations

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Correspondence to editorial 1 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
Haiyu Wang, Jinjun Chen
Clinical and Molecular Hepatology.2026; 32(1): e58. CrossRef
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
Absence of steatosis combined with cardiometabolic risk factors confers the highest hepatocellular carcinoma risk in treated chronic hepatitis B
Hung-Wei Wang, Hsueh-Chou Lai, Wei-Fan Hsu, Sheng-Hung Chen, Yi-Chun Kuo, Cheng-Yuan Peng
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Abdelrahman M. Attia, Jessica Liu, Walid S Ayoub, Yun Wang, Aarshi Vipani, Paul Martin, Hyunseok Kim, Ju Dong Yang
Current Hepatology Reports.2026;[Epub] CrossRef
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Mirko Zoncapè, Emmanuel A. Tsochatzis
Clinical and Molecular Hepatology.2025; 31(1): 268. CrossRef
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Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
Health Science Reports.2025;[Epub] CrossRef
A Review of Risk Prediction Model for Hepatocellular Carcinoma in Chronic Hepatitis B
Jiwon Yang, Mark D. Muthiah, Won-Mook Choi
Current Hepatology Reports.2025;[Epub] CrossRef
Head‐to‐Head Comparison of Long‐Term HCC Risk of Antivirals‐Treated Versus Untreated Low‐Level Viremia in HBV‐Compensated Cirrhosis
Nobuharu Tamaki, Daniel Q. Huang, Hyung Woong Lee, Soo Young Park, Yu Rim Lee, Dong Hyun Sinn, Tae Seop Lim, Hiroyuki Marusawa, Seng Gee Lim, Hironori Ochi, Masahiko Kondo, Yasushi Uchida, Haruhiko Kobashi, Koichiro Furuta, Masayuki Kurosaki, Beom Kyung K
Journal of Gastroenterology and Hepatology.2025; 40(6): 1595. CrossRef
Discovering the metabolic pathway of liver disease by breath mass spectrometry combined with machine learning
Xuanzhu Li, Wenbo Zhang, Tongtong Yang, Ying Zhang, Rui Su
Journal of Pharmaceutical and Biomedical Analysis.2025; 265: 116988. CrossRef
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Steatotic liver disease

The role of SPP1 in MASLD pathogenesis: Therapeutic insights into ursolic acid’s mechanisms of action: Correspondence to editorial on “Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease”: Yiyuan Zheng, Zhekun Xiong, Lina Zhao, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Fengbin Liu, Yong Li; Clin Mol Hepatol 2024;30(4):1019-1022.
Published online July 8, 2024; DOI: https://doi.org/10.3350/cmh.2024.0471

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Integrative Bioinformatics Analysis of Liver Transcriptomics and Serum Fibroblast Growth Factor 21 Protein Levels in Monitoring Progressive Fibrotic Liver Disease
Hawraa M. Alaa Alden, Haneen Rafea Ali, Afrah Jabbar Lazim, Ahmed AbdulJabbar Suleiman
Mathematical Biology and Bioinformatics.2026; 21(1): 175. CrossRef
Selenoprotein P deficiency in MASLD: association with insulin resistance and liver fibrosis: a prospective case-control study
Mona A Hegazy, Samar Saad Mohamed, Eman H Saad, Ahmed Abdelghani, Dalia Abd el Fattah, Mohamed Ahmed Elsayed Mekki, Mona Fathy, Nora Hassan, Omar Ashoush
BMC Gastroenterology.2026;[Epub] CrossRef
Single‑cell RNA sequencing analysis of intrahepatic cholangiocarcinoma reveals SPP1 facilitates disease progression via interaction with CD4+ T cells
Xian Lin, Huanyan Peng, Ke Liu, Wenqi Chen, Ximing Shao, Chun Ning, Hongchang Li, Dongye Yang
Oncology Letters.2025; 30(2): 1. CrossRef

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Steatotic liver disease

Correspondence to editorial on “Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy”: Qi Wang, Qingfa Bu, Haoming Zhou, Ling Lu; Clin Mol Hepatol 2024;30(4):1026-1027.
Published online July 8, 2024; DOI: https://doi.org/10.3350/cmh.2024.0470

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Steatotic liver disease

Macrophage ATG16L1: Potential candidate for metabolic dysfunction-associated steatohepatitis treatment: Editorial on “Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy”: Junjie Yu; Clin Mol Hepatol 2024;30(4):721-723.
Published online June 18, 2024; DOI: https://doi.org/10.3350/cmh.2024.0443

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Steatotic liver disease

Ursolic acid: A promising therapeutic agent for metabolic dysfunction-associated steatotic liver disease via inhibition of SPP1-induced Th17 cell differentiation: Editorial on “Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease”: So Jung Kim, Jeongeun Hyun; Clin Mol Hepatol 2024;30(4):709-713.
Published online June 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0412

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Ursolic acid in colorectal cancer: mechanisms, current status, challenges, and future research directions
Huici Zhang, Xiaoyu Zhang, Xijun Ma, Xuan Wang
Pharmacological Reports.2025; 77(1): 72. CrossRef
Therapeutic applications of ursolic acid: a comprehensive review and utilization of predictive tools
Sherien M. Bakry, Riham A. El-Shiekh, Shymaa Hatem, Asmaa A. Mandour, Ahmed M. El-Dessouki, Abeer Bishr, Heba Elosaily, Ahmed F. Mohamed, Shaza M. Elhusseiny
Future Journal of Pharmaceutical Sciences.2025;[Epub] CrossRef
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Chao-Jun Yang, Bo Fu, Yi-Fan Huang, Jing-Yi Wu, Zhi-Xing Fan, Ya-Hui Li
Reviews in Cardiovascular Medicine.2025;[Epub] CrossRef
The role of SPP1 in MASLD pathogenesis: Therapeutic insights into ursolic acid’s mechanisms of action: Correspondence to editorial on “Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic
Yiyuan Zheng, Zhekun Xiong, Lina Zhao, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Fengbin Liu, Yong Li
Clinical and Molecular Hepatology.2024; 30(4): 1019. CrossRef

5,982 View
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3 Web of Science
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Steatotic liver disease

Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy: Qi Wang, Qingfa Bu, Zibo Xu, Yuan Liang, Jinren Zhou, Yufeng Pan, Haoming Zhou, Ling Lu; Clin Mol Hepatol 2024;30(3):515-538.
Published online May 10, 2024; DOI: https://doi.org/10.3350/cmh.2024.0107

Background/Aims
Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH.
Methods
Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH.
Results
Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression.
Conclusions
ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

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Qiqi Zhao, Shengwen Lu, Yu Guan, Zhiwen Sun, Shi Qiu, Aihua Zhang
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Autoimmunity, diet and autophagy
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Binhui Zhou, Bowen Zhang, Yingcheng Qi, Sainan Li, Tingting Liu, Tong Li, Ying Wang, Haifeng Wang, Jiaqi Lu, Fei Cao, Xiaohong Kang, Eryan Kong, Yinming Liang
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Biochemical Pharmacology.2026; 250: 118031. CrossRef
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JHEP Reports.2025; 7(5): 101330. CrossRef
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Yan Bai, Xinyu Zhan, Qing Zhu, Xingyue Ji, Yingying Lu, Yiyun Gao, Fei Li, Zhu Guan, Haoming Zhou, Zhuqing Rao
Clinical and Translational Medicine.2025;[Epub] CrossRef
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Yi Chen, Kangjie Xie, Caiyang Chen, Xihui Wang, Chenchen Ma, Zhangxiang Huang, Yingfu Jiao, Weifeng Yu
Molecular Medicine.2025;[Epub] CrossRef
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Yiwei Shang, Jun Yuan, Shaoting Wang, Wenfang He, Binqi Wang, Danna Zheng, Nan Yang, Juan Jin, Qiang He
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Macrophage ATG16L1: Potential candidate for metabolic dysfunction-associated steatohepatitis treatment: Editorial on “Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy”
Junjie Yu
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Correspondence to editorial on “Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy”
Qi Wang, Qingfa Bu, Haoming Zhou, Ling Lu
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Steatotic liver disease

Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease: Yiyuan Zheng, Lina Zhao, Zhekun Xiong, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Yugang Fu, Simin Gu, Chong Chen, Jiacheng Li, Yingying Zhu, Jing Liu, Fengbin Liu, Yong Li; Clin Mol Hepatol 2024;30(3):449-467.
Published online April 16, 2024; DOI: https://doi.org/10.3350/cmh.2024.0047

Background/Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD.
Methods
Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4⁺ T cells were isolated and stimulated to demonstrate our findings.
Results
In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression.
Conclusions
Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

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Viral hepatitis

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients: Man-Fung Yuen, Wan-Long Chuang, Cheng-Yuan Peng, Wen-Juei Jeng, Wei-Wen Su, Ting-Tsung Chang, Chi-Yi Chen, Yao-Chun Hsu, Guy De La Rosa, Alaa Ahmad, Ed Luo, Annie L. Conery; Clin Mol Hepatol 2024;30(3):375-387.
Published online March 26, 2024; DOI: https://doi.org/10.3350/cmh.2023.0535

Background/Aims
Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection.
Methods
Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days.
Results
A dose-related increase in EDP-514 exposure (AUC_last and C_max) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log₁₀ IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log₁₀ U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths.
Conclusions
In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Citations

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