Clinical and Molecular Hepatology

"Alcohol"

Editorials

Ethanol‑Specific Stress and RAB25/GCN1 Signaling: Emerging Perspectives in Alcohol‑Associated Liver Disease: Miaomiao Wu, Qianying Cheng, Li Zuo, Hua Wang; Received December 1, 2025 Accepted December 2, 2025 Published online December 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.1360 [Accepted]

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Mechanistic Insights into a Noncanonical RAB25–GCN1 axis in ALD: Editorial on “RAB25/GCN1 signaling promotes ER stress to mediate alcohol-associated liver disease progression”: Seol Hee Park, Wonhyo Seo; Received November 27, 2025 Accepted December 2, 2025 Published online December 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.1346 [Accepted]

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Review Article

Novel Biomarkers for Alcohol-Associated Liver Disease and Their Implications Across Clinical Settings: Kaanthi Rama, Vinay Jahagirdar, Francisco Idalsoaga, Hanna Blaney, S. Fisher Rhoads, Luis Antonio Díaz, Marco Arrese, Juan Pablo Arab; Received August 15, 2025 Accepted November 17, 2025 Published online November 25, 2025; DOI: https://doi.org/10.3350/cmh.2025.0921 [Accepted]

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

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Original Article

RAB25/GCN1 Signaling Promotes ER Stress to Mediate Alcohol-associated Liver Disease Progression: Xue-Wen Liu, Zi-Bin Zhan, Ze-Hua Li, Yue Zhang, Xue-Yan Qiao, Xin-Ming Li, Xiang-Jing Liang, Kun-Hao Bai, Xian-Feng Xia, Fan-Hong Zeng, Yi Gao, Jun Weng; Received May 28, 2025 Accepted September 2, 2025 Published online September 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0559 [Accepted]

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

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Research Letter

Contemporary Trends in Extrahepatic Mortality of Chronic Liver Disease in the United States from 2014 to 2023: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed; Received July 23, 2025 Accepted July 23, 2025 Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0802 [Accepted]

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Correspondence

Reply to the letter to the editor on “Re: “Sex Disparities in Alcohol-Associated Liver Disease and Subtype Differences in Alcohol-attributable Cancers in the United States”: Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang; Received June 5, 2025 Accepted June 13, 2025 Published online June 17, 2025; DOI: https://doi.org/10.3350/cmh.2025.0594 [Accepted]

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Sex chromosomes/hormones and the tumor microenvironment of non-reproductive cancers
Chun-Miao Zhang, Zhong-Bo Ge, Hai-Hong Zhou, Meng-Xiao Wei, Xin-Yuan Ding, Zhe-Zheng Lin, Ming-Yu Wang, Cai-Juan Bai
Frontiers in Immunology.2025;[Epub] CrossRef
Rising burden of steatotic liver disease in women of childbearing age and projections till 2035
Youxin Wang, Ruiqiu Chen, Shi Yan Lee, Eunice X.X. Tan, Mark Muthiah, Zhou Yu, Margaret L.P. Teng, Jazleen Leo, Cheng Han Ng, Ashok Choudhury, Daniel Q. Huang
JHEP Reports.2025; : 101646. CrossRef

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Research Letters

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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Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2025; 49(11): 2451. CrossRef

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Contemporary burden of mortality from chronic liver disease by sex and race/ethnicity in the United States: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed; Clin Mol Hepatol 2025;31(3):e268-e272.
Published online May 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0384

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Rising drug overdose deaths in chronic liver disease in the United States, 2015–2023
Donghee Kim, Brittany B Dennis, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed
Clinical and Molecular Hepatology.2025; 31(3): e277. CrossRef
Advancing Policy and Practice in Alcohol-Associated Liver Disease and Alcohol-Attributable Cancer: Correspondence to the editorial on “Rising Burden of Alcohol-Associated Liver Disease and Cancers: Insights into Sex Disparities and Policy Implications”
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang
Clinical and Molecular Hepatology.2025;[Epub] CrossRef
Extrahepatic manifestation of metabolic dysfunction-associated steatotic liver disease
Anoushka Shenoy, Aijaz Ahmed, Donghee Kim
Metabolism and Target Organ Damage.2025;[Epub] CrossRef

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Original Articles

Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study: Xianhua Mao, Xinrong Zhang, Rongtao Lai, Ka-Shing Cheung, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen; Clin Mol Hepatol 2025;31(3):1084-1099.
Published online April 23, 2025; DOI: https://doi.org/10.3350/cmh.2024.1096

Background/Aims
Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.
Methods
Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan^® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).
Results
In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77.
Conclusions
In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.

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Evaluating causal protective effect of dual GLP-1R/GIPR agonists on MASLD: A Mendelian randomization and colocalization study
Yangke Cai, Siyuan Xie, Liyi Xu, Jiamin Chen, Jianting Cai
European Journal of Pharmacology.2025; 1005: 178088. CrossRef
Impaired Thyroid Hormone Sensitivity is Associated with Increased Risk of Liver Fibrosis in Euthyroid Population: A Cross-Sectional Analysis of NHANES
Xingyu Yao, Kaiwen Xiao, Hein Ko Oo
Hormone and Metabolic Research.2025; 57(09): 511. CrossRef

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Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States: Pojsakorn Danpanichkul, Yanfang Pang, Tanuj Mahendru, Primrose Tothanarungroj, Luis Antonio Díaz, Juan Pablo Arab, Pimtawan Jatupornpakdee, Mark D. Muthiah, Kwanjit Duangsonk, Won-Mook Choi, Daniel Q. Huang, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2025;31(3):1058-1070.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0169

Background/Aims
Harmful alcohol use is a substantial contributor to liver diseases, liver cancer, and extrahepatic neoplasms. Patterns of alcohol consumption have shifted over recent decades. This study evaluates trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers in the United States (US) from 2000 to 2021.
Methods
Using the methodological framework of the Global Burden of Disease Study 2021, we analyzed trends in incidence, prevalence, and mortality from ALD and alcohol-attributable cancers in the US.
Results
In 2021, there were 28,340 new cases of ALD, 227,730 prevalent cases, and 21,860 deaths attributed to ALD in the US. From 2000 to 2021, ALD incidence, prevalence, and mortality increased by 43%, 36%, and 79%, respectively. The age-standardized incidence and death rate of ALD rose disproportionately among females compared to males. For alcohol-attributable cancers, primary liver cancer, colorectal cancer, and esophageal cancer accounted for the largest share of deaths in 2021. Age-standardized death rates increased significantly for primary liver cancer (annual percent change [APC] 2.21%, 95% confidence interval [CI] 1.70–2.73%) and other pharyngeal cancer (APC 1.35%, 95% CI 1.08–1.62%).
Conclusions
The burden of ALD is substantial and continues to rise in the US, with a particularly notable increase among females. Mortality from alcohol-attributable cancers is also increasing, mainly driven by primary liver cancer and pharyngeal cancer. However, system-wise, gastrointestinal cancer had the highest death attributable to alcohol. These findings highlight the urgent need for public health strategies to tackle ALD, primary liver cancer, and alcoholattributable extrahepatic malignancies.

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Rising burden of steatotic liver disease in women of childbearing age and projections to 2035
Youxin Wang, Ruiqiu Chen, Shi Yan Lee, Eunice X.X. Tan, Mark Muthiah, Zhou Yu, Margaret L.P. Teng, Jazleen Leo, Cheng Han Ng, Ashok Choudhury, Daniel Q. Huang
JHEP Reports.2026; 8(1): 101646. CrossRef
MetALD: new insights and unraveling therapeutic potential
Yue Feng, PanShiLi Han, Tao Liu, YanHang Gao
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
Sex Disparity in Major Adverse Liver Outcome and Major Adverse Cardiac Event in Alcohol‐Associated Liver Disease
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Mark D. Muthiah, Suthat Liangpunsakul
Liver International.2025;[Epub] CrossRef
Advancing Policy and Practice in Alcohol-Associated Liver Disease and Alcohol-Attributable Cancer: Correspondence to the editorial on “Rising Burden of Alcohol-Associated Liver Disease and Cancers: Insights into Sex Disparities and Policy Implications”
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang
Clinical and Molecular Hepatology.2025;[Epub] CrossRef
Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2025; 49(11): 2451. CrossRef
Consumo de alcohol y cirrosis en mujeres: un riesgo subestimado
P. Huerta, J.P. Arab, L.A. Díaz
Revista de Gastroenterología de México.2025; 90(4): 509. CrossRef
Alcohol use and cirrhosis in women: An underestimated risk
P. Huerta, J.P. Arab, L.A. Díaz
Revista de Gastroenterología de México (English Edition).2025; 90(4): 509. CrossRef

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Research Letter

Lipidomic analysis of alcohol use disorder patients revealed the biomarkers for alcohol-related liver disease susceptibility: Dongyao Wang, Hongwei Zhang, Yuxiao Tang; Clin Mol Hepatol 2025;31(3):e259-e262.
Published online April 2, 2025; DOI: https://doi.org/10.3350/cmh.2025.0227

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Targeting Annexin A2 to reactivate tumor-associated antigens presentation and relieve immune tolerance in liver cancer
Yuxiao Tang, Jianxin Yang, Qicong Shen, Zelong Gao, Mengpu Wu, Chenghua Wu, Jicong Du, Min Li, Changquan Ling, Feng Lu, Yifeng Chai, Xin Dong, Jianxin Qian, Chenqi Li, Feng Xie, Zhenhong Guo, Hui Shen, Dongyao Wang
Journal for ImmunoTherapy of Cancer.2025; 13(6): e011716. CrossRef

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Special Issue

Steatotic liver disease

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

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Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma
Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
Cancers.2025; 17(9): 1548. CrossRef
Metabolic Dysfunction-Associated Steatotic Liver Disease, Recent Revision of Terminology and Its Implications
Hyo Young Lee, Eileen L. Yoon
The Korean Journal of Gastroenterology.2025; 85(2): 126. CrossRef
Advances in identifying risk factors of metabolic dysfunction-associated alcohol-related liver disease
Rui-Qi Ye, Yi-Fan Chen, Chang Ma, Xi Cheng, Wei Guo, Sha Li
Biomedicine & Pharmacotherapy.2025; 188: 118191. CrossRef
A Case Report of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) with Improved Cardiometabolic Risk Factors Following Treatment with Saenggangunbi-tang
Eun Kyung Lee, Min Jeong Park, Youngchul Kim, Jang-Hoon Lee
The Journal of Internal Korean Medicine.2025; 46(2): 303. CrossRef
Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review
Erdenetsogt Dungubat, Kohei Fujikura, Masahiko Kuroda, Toshio Fukusato, Yoshihisa Takahashi
Nutrients.2025; 17(13): 2211. CrossRef
Associations between steatotic liver disease subtypes and incident atrial fibrillation in young adults: a nationwide cohort study
Jeayeon Park, Goh Eun Chung, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Eun Ju Cho
Cardiovascular Diabetology.2025;[Epub] CrossRef
Second-line antidiabetic drugs: friend or foe of the liver
Jiwon Yang, Gunho Kim, Ju Hyun Shim, Jihyun An
Journal of Liver Cancer.2025; 25(2): 187. CrossRef
Extrahepatic manifestation of metabolic dysfunction-associated steatotic liver disease
Anoushka Shenoy, Aijaz Ahmed, Donghee Kim
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
2025 Clinical Practice Guidelines for Diabetes: Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
Jaehyun Bae
The Journal of Korean Diabetes.2025; 26(3): 172. CrossRef
Paired snRNA-seq and scRNA-seq analysis of MASLD patients to identify early-stage markers for disease progression
Suebin Park, Su-Hyeon Lee, Se-eun Han, Beom Kyung Kim, Byungjin Hwang
Hepatology Communications.2025;[Epub] CrossRef
Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease
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International Journal of Molecular Sciences.2025; 26(19): 9594. CrossRef
Discovery of ultrasound-derived fat fraction as a non-invasive tool for MASLD diagnosis
Huiru Jin, Mengfan Jiao, Chengxiao Yu, Tingting Ren, Qingling Chen, Zixing Dai, Erfu Xie, Longfeng Jiang, Yuwen Li
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Risk of Esophageal and Gastric Cancer by Histologic Subtype in Steatotic Liver Disease: A UK Biobank Study
Donghoon Kang, Ji Won Han, Kenneth R. Muir, Artitaya Lophatananon, Jongin Lee
Cancers.2025; 17(21): 3416. CrossRef

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Correspondence

Alcohol-related liver disease

Correspondence to editorial on “Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000-2021”: Pojsakorn Danpanichkul, Luis Antonio Diaz, Kanokphong Suparan, Karn Wijarnpreecha, Juan Pablo Arab; Clin Mol Hepatol 2025;31(2):e200-e202.
Published online February 17, 2025; DOI: https://doi.org/10.3350/cmh.2025.0166

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Editorial

Alcohol-related liver disease

Burden of alcohol use disorder, alcohol-related liver disease, and alcohol-related liver cancer: Editorial on “Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021: Youxin Wang, Noriko Oza, Jazleen Leo, Ashok Choudhury, Daniel Q. Huang; Clin Mol Hepatol 2025;31(2):654-657.
Published online February 10, 2025; DOI: https://doi.org/10.3350/cmh.2025.0133

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Correspondence to editorial on “Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000-2021”
Pojsakorn Danpanichkul, Luis Antonio Diaz, Kanokphong Suparan, Karn Wijarnpreecha, Juan Pablo Arab
Clinical and Molecular Hepatology.2025; 31(2): e200. CrossRef

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Letters to the Editor

Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”: Chi-Kuei Hsu, Po-Yu Huang, Chih-Cheng Lai; Clin Mol Hepatol 2025;31(3):e247-e248.
Published online February 6, 2025; DOI: https://doi.org/10.3350/cmh.2025.0073

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What is new in the 2024 Chinese guidelines for fatty liver disease?: Rui-Xu Yang, Vincent Wai-Sun Wong, Jian-Gao Fan; Clin Mol Hepatol 2025;31(3):e239-e246.
Published online January 21, 2025; DOI: https://doi.org/10.3350/cmh.2024.1165

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Original Articles

Alcohol-related liver disease

Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021: Pojsakorn Danpanichkul, Luis Antonio Díaz, Kanokphong Suparan, Primrose Tothanarungroj, Supapitch Sirimangklanurak, Thanida Auttapracha, Hanna L. Blaney, Banthoon Sukphutanan, Yanfang Pang, Siwanart Kongarin, Francisco Idalsoaga, Eduardo Fuentes-López, Lorenzo Leggio, Mazen Noureddin, Trenton M. White, Alexandre Louvet, Philippe Mathurin, Rohit Loomba, Patrick S. Kamath, Jürgen Rehm, Jeffrey V. Lazarus, Karn Wijarnpreecha, Juan Pablo Arab; Clin Mol Hepatol 2025;31(2):525-547.
Published online January 9, 2025; DOI: https://doi.org/10.3350/cmh.2024.0835

Background/Aims
Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021.
Methods
We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.
Results
In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.
Conclusions
Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.

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Letter: Global Burden of Metabolic Dysfunction‐Associated Steatotic Liver Disease‐Related Liver Cancer—Results From the Global Burden of Disease Study 2021. Authors' Reply
Pojsakorn Danpanichkul, Donghee Kim, Markos Kalligeros, Amit G. Singal, Ju Dong Yang, Karn Wijarnpreecha
Alimentary Pharmacology & Therapeutics.2025; 61(6): 1080. CrossRef
Updated recommendations for the management of metabolic dysfunction–associated steatotic liver disease (MASLD) by the Latin American working group
Luis Antonio Diaz, Juan Pablo Arab, Francisco Idalsoaga, Javiera Perelli, Javier Vega, Melisa Dirchwolf, Javiera Carreño, Bárbara Samith, Cynthia Valério, Rodrigo Oliveira Moreira, Mónica Acevedo, Javier Brahm, Nelia Hernández, Adrian Gadano, Claudia P. O
Annals of Hepatology.2025; 30(2): 101903. CrossRef
Editorial: Balancing the Yin and Yang of Alcohol‐Associated Liver Disease—Integrating Pathophysiology, Liver‐Directed Therapy, and Addiction Management. Authors' Reply
Luis Antonio Díaz, Rohit Loomba
Alimentary Pharmacology & Therapeutics.2025; 61(7): 1256. CrossRef
Implementing public health policy to tackle alcohol-related harms
Pojsakorn Danpanichkul, Karn Wijarnpreecha
The Lancet Public Health.2025; 10(5): e350. CrossRef
Alcohol-Associated Liver Disease and Risk Stratification for Hepatocellular Carcinoma: A Comprehensive Review
Jaeyoun Choi, Hyun-seok Kim
Current Hepatology Reports.2025;[Epub] CrossRef
Public Health Policies and Strategies to Prevent Alcohol-Related Morbidity and Mortality
Roba El Zibaoui, Luis Antonio Díaz, Francisco Idalsoaga, Juan Pablo Arab
Current Hepatology Reports.2025;[Epub] CrossRef
Tetramethylpyrazine: A fermented alcohol product that mitigates alcoholic liver disease in mice
Qing Pu, Han Gao, Dake Xiao, Manyuan Wang, Zhiyun Yang, Qiang He, Min Liu, Xuejin Zhu, Tao Pan, Zhitao Ma, Jiabo Wang, Yao Liu
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Safety and Tolerability of Injectable Extended‐Release Naltrexone for the Management of Alcohol Use Disorder in Advanced Alcohol‐Associated Liver Disease
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Sex Disparity in Major Adverse Liver Outcome and Major Adverse Cardiac Event in Alcohol‐Associated Liver Disease
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Mark D. Muthiah, Suthat Liangpunsakul
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High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease: Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao; Clin Mol Hepatol 2025;31(3):796-809.
Published online January 6, 2025; DOI: https://doi.org/10.3350/cmh.2024.0822

Background/Aims
There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods
Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results
Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0–100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38–10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97–31.30) and MASLD (aSHR 4.23; 95% CI 1.43–12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions
The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.

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Editorial

Steatotic liver disease

Vibration-controlled transient elastography in shaping the epidemiology and management of steatotic liver disease: Editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”: Xiao-Dong Zhou, Terry Cheuk-Fung Yip, Daniel Q Huang, Mark Dhinesh Muthiah, Mazen Noureddin, Ming-Hua Zheng; Clin Mol Hepatol 2025;31(2):620-624.
Published online December 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.1131

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Original Article

Steatotic liver disease

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):382-393.
Published online November 29, 2024; DOI: https://doi.org/10.3350/cmh.2024.0987

Background/Aims
Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.
Methods
Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.
Results
The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4–36.7). Within this category, the age-adjusted prevalence for MASLD was 31.9% (95% CI 30.4–33.4), MetALD 2.2% (95% CI 1.8–2.6), and ALD 0.8% (95% CI 0.6–1.1). The prevalence of SLD and MASLD showed a statistically insignificant decrease during COVID-19, while ALD increased without significance. In contrast, the prevalence of advanced fibrosis in SLD was significantly higher during the COVID-19 era, at 9.8% for 285 dB/m and 7.8% for 263 dB/m, compared to 7.4% (P=0.039) and 6% (P=0.041) in the pre-COVID-19 era. The proportion of advanced fibrosis and cirrhosis in individuals with ALD was two-fold higher than MASLD and MetALD, largely due to increases during the COVID-19 era.
Conclusions
While the prevalence of SLD and its subcategories remained stable, there was a significant increase in advanced fibrosis among SLD individuals during the COVID-19 era, with ALD having a proportion of advanced fibrosis and cirrhosis that was twice as high as MASLD and MetALD.

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Reviews

Steatotic liver disease

Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease: Huma Saeed, Luis Antonio Díaz, Antonio Gil-Gómez, Jeremy Burton, Jasmohan S. Bajaj, Manuel Romero-Gomez, Marco Arrese, Juan Pablo Arab, Mohammad Qasim Khan; Clin Mol Hepatol 2025;31(Suppl):S94-S111.
Published online November 28, 2024; DOI: https://doi.org/10.3350/cmh.2024.0811

Abstract
PDF

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.

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Viral hepatitis

Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B: Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto; Clin Mol Hepatol 2025;31(Suppl):S182-S195.
Published online November 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0837

Abstract
PDF

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

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Alcohol-related liver disease

Alcohol-associated liver disease: Natural history, management and novel targeted therapies: Edilmar Alvarado-Tapias, Elisa Pose, Jordi Gratacós-Ginès, Ana Clemente-Sánchez, Hugo López-Pelayo, Ramón Bataller; Clin Mol Hepatol 2025;31(Suppl):S112-S133.
Published online October 31, 2024; DOI: https://doi.org/10.3350/cmh.2024.0709

Abstract
PDF

Alcohol consumption is a leading cause of preventable morbidity and mortality worldwide and the primary cause of advanced liver disease. Alcohol use disorder is a chronic, frequently relapsing condition characterized by persistent alcohol consumption despite its negative consequences. Alcohol-associated liver disease (ALD) encompasses a series of stages, from fatty liver (steatosis) to inflammation (steatohepatitis), fibrosis, and, ultimately, liver cirrhosis and its complications. The development of ALD is complex, involving both genetic and environmental factors, yet the exact mechanisms at play remain unclear. Alcohol-associated hepatitis (AH), a severe form of ALD, presents with sudden jaundice and liver failure. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD to stop the progression of the disease, making alcohol abstinence the most effective way to improve prognosis across all stages of ALD. For patients with advanced ALD who do not respond to medical therapy, liver transplantation is the only option that can improve prognosis. Recently, AH has become an early indication for liver transplantation in non-responders to medical treatment, showing promising results in carefully selected patients. This review provides an update on the epidemiology, natural history, pathogenesis, and current treatments for ALD. A deeper insight into novel targeted therapies investigated for AH focusing on new pathophysiologically-based agents is also discussed, including anti-inflammatory and antioxidative stress drugs, gut-liver axis modulators, and hepatocyte regenerative molecules.

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Correspondence

Liver fibrosis, cirrhosis, and portal hypertension

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

4,780 View
39 Download

Editorial

Alcohol-related liver disease

The urgent need for multidisciplinary approaches in managing alcohol-associated liver disease: Editorial on “The prognostic impact of psychiatric intervention on alcohol-associated liver disease: The UK Biobank cohort study”: Soon Sun Kim, Jae Youn Cheong; Clin Mol Hepatol 2025;31(1):316-318.
Published online October 7, 2024; DOI: https://doi.org/10.3350/cmh.2024.0847

5,117 View
63 Download

Correspondence

Steatotic liver disease

Correspondence to editorial on “Optimal cutoffs 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”: Jung Hwan Yu, Seung Up Kim; Clin Mol Hepatol 2025;31(1):e52-e54.
Published online September 24, 2024; DOI: https://doi.org/10.3350/cmh.2024.0815

6,382 View
37 Download

Letter to the Editor

Steatotic liver disease

Letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”: Xiao-Song Li, Xi-Ping Shen, Hang Li; Clin Mol Hepatol 2025;31(1):e15-e16.
Published online September 12, 2024; DOI: https://doi.org/10.3350/cmh.2024.0784

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Correspondence to letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
Yuri Cho, Dae Won Jun
Clinical and Molecular Hepatology.2025; 31(1): e103. CrossRef

4,291 View
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1 Web of Science
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Correspondence

Steatotic liver disease

Correspondence to editorial on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”: Hayeon Kim, Min Jeong Park, Myeong Gyu Kim, Kyungim Kim; Clin Mol Hepatol 2024;30(4):989-991.
Published online August 27, 2024; DOI: https://doi.org/10.3350/cmh.2024.0705

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Reply to correspondence on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”
Tian-Yi Ren, Mohammed Eslam, Jian-Gao Fan
Clinical and Molecular Hepatology.2024; 30(4): 1039. CrossRef

4,177 View
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Crossref

Original Articles

Alcohol-related liver disease

The prognostic impact of psychiatric intervention on alcohol-associated liver disease: The UK Biobank cohort study: Keungmo Yang, Sunghwan Kim, Hyun Yang, Sheng-Min Wang, Bumseok Jeong, Hyun Kook Lim, Si Hyun Bae; Clin Mol Hepatol 2024;30(4):929-942.
Published online August 27, 2024; DOI: https://doi.org/10.3350/cmh.2024.0278

Background/Aims
Alcohol-associated liver disease (ALD) is a public health concern. ALD patients often have psychiatric comorbidities, but the effects of psychiatric interventions on ALD are not well-established. This study explores the prognostic impact of psychiatric intervention on ALD within UK Biobank cohort.
Methods
This population-based study included 2,417 ALD patients from the UK Biobank cohort. Psychiatric intervention was defined by a consultation with psychiatrists during hospitalization or a history of medication related to alcohol use disorder and psychiatric comorbidities. Survival analysis was conducted, incorporating propensity score matching (PSM), to precisely assess the impact of psychiatric intervention.
Results
Among 2,417 ALD patients, those with F10 (mental disorders due to alcohol) codes had poorer survival outcomes. Psychiatric intervention significantly improved the outcomes of both all-cause and liver-related mortality and reduced the incidence of liver cirrhosis. In subgroup or 2-year landmark analyses, psychiatric intervention consistently showed a survival benefit in ALD patients. In the multivariate analysis, psychiatric intervention was identified as a favorable prognostic factor (hazard ratio, 0.780; P=0.002 after PSM).
Conclusions
This study demonstrates the favorable effect of psychiatric intervention in ALD patients with psychiatric comorbidities. These findings emphasize the importance of integrated management for ALD patients to address both their medical and psychiatric aspects. Therefore, we suggest the potential benefits of early psychiatric interventions in improving survival outcomes in ALD.

Citations

Citations to this article as recorded by

The urgent need for multidisciplinary approaches in managing alcohol-associated liver disease: Editorial on “The prognostic impact of psychiatric intervention on alcohol-associated liver disease: The UK Biobank cohort study”
Soon Sun Kim, Jae Youn Cheong
Clinical and Molecular Hepatology.2025; 31(1): 316. CrossRef

7,182 View
163 Download
2 Web of Science
Crossref

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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Reply to Correspondence

Steatotic liver disease

Reply to correspondence on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”: Jae Hyun Bae; Clin Mol Hepatol 2024;30(4):1047-1049.
Published online August 19, 2024; DOI: https://doi.org/10.3350/cmh.2024.0666

3,950 View
58 Download

Editorial

Steatotic liver disease

Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease outcomes: A call for culturally sensitive interventions: Editorial on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”: Jae Hyun Bae; Clin Mol Hepatol 2024;30(4):665-668.
Published online July 29, 2024; DOI: https://doi.org/10.3350/cmh.2024.0562

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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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Review

Steatotic liver disease

Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease: Yue Wang, Sherlot Juan Song, Yichong Jiang, Jimmy Che-To Lai, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip; Clin Mol Hepatol 2025;31(Suppl):S51-S75.
Published online June 27, 2024; DOI: https://doi.org/10.3350/cmh.2024.0246

Abstract
PDF

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

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Published online June 18, 2024; DOI: https://doi.org/10.3350/cmh.2024.0443

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Changing from NAFLD to MASLD: Prevalence and progression of ASCVD risk are similar between NAFLD and MASLD in Asia: Hiroyuki Suzuki, Tsubasa Tsutsumi, Machiko Kawaguchi, Keisuke Amano, Takumi Kawaguchi; Clin Mol Hepatol 2024;30(3):577-579.
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Steatotic liver disease

Similar respiratory function including chronic obstructive pulmonary disease between non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease: Tsubasa Tsutsumi, Dan Nakano, Machiko Kawaguchi, Hirokazu Takahashi, Takumi Kawaguchi; Clin Mol Hepatol 2024;30(2):266-268.
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Published online November 28, 2023; DOI: https://doi.org/10.3350/cmh.2023.0500

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Letter to the Editor

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Letter regarding “Waiting for the changes after the adoption of steatotic liver disease”: Kuo Chao Yew, Sunny H. Wong, Vincent Wai-Sun Wong, Hazel H. Oon; Clin Mol Hepatol 2024;30(1):118-120.
Published online November 14, 2023; DOI: https://doi.org/10.3350/cmh.2023.0472

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Special Review

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Waiting for the changes after the adoption of steatotic liver disease: Eileen L. Yoon, Dae Won Jun; Clin Mol Hepatol 2023;29(4):844-850.
Published online September 6, 2023; DOI: https://doi.org/10.3350/cmh.2023.0291

Abstract
PDF

Steatotic liver disease was suggested as an overarching term encompassing various etiologies of hepatic steatosis. Experts from multinational liver societies went through the Delphi process, including four rounds of surveys, and consented to adopt a new nomenclature and definition instead of the conventional nonalcoholic fatty liver disease (NAFLD). This was to improve the understanding of the patients and primary care physicians, with an explanation of the pathophysiology in the name of the disease. Also, it could minimize the stigmatization of patients by using the histological neutral term “steatosis” instead of “fatty”. Herein, we will discuss the changes and continuity between the two nomenclatures, metabolic dysfunction-associated steatotic liver disease (MASLD) and NAFLD, as well as the challenges to MASLD which need to be addressed in future.

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Correspondence

Steatotic liver disease

Correspondence on Letter regarding “Risk factors in nonalcoholic fatty liver disease”: Eileen L. Yoon, Dae Won Jun; Clin Mol Hepatol 2023;29(4):1050-1051.
Published online August 29, 2023; DOI: https://doi.org/10.3350/cmh.2023.0310

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Citations to this article as recorded by

Reply to correspondence on “Prognosis of biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: A sub-analysis of the CLIONE study”
Eileen Laurel Yoon, Dae Won Jun
Clinical and Molecular Hepatology.2024; 30(4): 1033. CrossRef

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Special Review

Steatotic liver disease

Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity: Gi-Ae Kim, Joon Ho Moon, Won Kim; Clin Mol Hepatol 2023;29(4):831-843.
Published online August 25, 2023; DOI: https://doi.org/10.3350/cmh.2023.0277

Abstract
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The existing term non-alcoholic fatty liver disease (NAFLD) has raised substantial concerns due to its inherent disadvantages of using exclusionary diagnostic criteria and the stigmatizing word ‘fatty.’ Three pan-national liver associations set out to explore a new nomenclature to replace both NAFLD and its suggested alternative, metabolic (dysfunction)-associated fatty liver disease (MAFLD). They surveyed if a change in nomenclature and/or definition is favored and which nomenclature best communicates disease characteristics and increases awareness. In lieu of NAFLD/MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD) has been chosen, and an umbrella term, steatotic liver disease (SLD), encompassing the whole spectrum of liver disease, has been proposed. It has been suggested that cardiometabolic risk factors should be considered when categorizing SLD patients. Furthermore, a new subcategory, MASLD with increased alcohol intake (MetALD), casts light on a neglected group of patients with moderate or more alcohol consumption. The importance of metabolic dysfunction was acknowledged in this new nomenclature, but the precise contribution of metabolic dysfunction and alcohol consumption to the development and progression of SLD remains unclear. Herein, we review hepatologists’ and endocrinologists’ perspectives on the new nomenclature, along with its possible impact on clinical practice. Although it is premature to predict the settlement of the new nomenclature, this review may help build more evidence for a soft landing of it in the future.

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Editorial

Steatotic liver disease

Lean or Non-obese Nonalcoholic Fatty Liver Disease Patients: Are They Really Lean?: Eugene Han, Yong-ho Lee; Clin Mol Hepatol 2023;29(4):980-983.
Published online August 16, 2023; DOI: https://doi.org/10.3350/cmh.2023.0250

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Original Article

Steatotic liver disease

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity: Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe; Clin Mol Hepatol 2023;29(4):987-1001.
Published online July 5, 2023; DOI: https://doi.org/10.3350/cmh.2023.0035

Background/Aims
To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis.
Methods
This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3^rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography.
Results
Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors.
Conclusions
In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

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Steatotic liver disease

Correspondence on Letter regarding “Non-alcoholic fatty liver disease: Definition and subtypes”: Seul Ki Han, Soon Koo Baik, Moon Young Kim; Clin Mol Hepatol 2023;29(3):817-819.
Published online May 17, 2023; DOI: https://doi.org/10.3350/cmh.2023.0155

Citations

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