The 2023 multisociety Delphi consensus redefined the nomenclature for steatotic liver disease (SLD) by replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) and introducing metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD). This revised framework is expected to enhance epidemiological surveillance, phenotyping of SLD, and public health interpretation. This review summarizes contemporary literature on the global epidemiology, disease burden, and comparative outcomes of MASLD, MetALD, and ALD. MASLD remains the most prevalent SLD subtype, affecting approximately 30%–40% of adults worldwide, with a rising burden over time. MASLD rapidly increases in regions with lower sociodemographic indices. MetALD affects an estimated 2%–8% of adults and represents an important overlap phenotype, although its prevalence is likely underestimated due to frequent underreporting of alcohol intake. ALD has a lower prevalence but contributes disproportionately to higher liver-related morbidity and mortality and is reported to have a marked regional variation linked to patterns of alcohol consumption. SLD has emerged as a major global epidemic, with MASLD imposing the greatest population burden and MetALD/ALD disproportionately contributing to severe liver-related outcomes. Across SLD phenotypes, cardiovascular disease is a major cause of death in non-cirrhotic disease, while liver-related outcomes show a gradient associated with alcohol exposure. Significant epidemiologic limitations include heterogeneity in the steatosis assessment methods, limited availability of cardiometabolic criteria, and reliance on self-reported alcohol consumption. Mitigating this growing burden of SLD requires public health policies that incorporate metabolic risk prevention, regulation of alcohol consumption, and early risk stratification.
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 Liver International.2026;[Epub] CrossRef
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Extrahepatic mortality associated with chronic liver disease with or without cirrhosis from 2014 to 2024 Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed Clinical and Molecular Hepatology.2026; 32(2): e194. CrossRef
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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 Liver International.2026;[Epub] CrossRef
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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 Liver International.2026;[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
Reply to correspondence 1 on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States” Sung-Eun Kim Clinical and Molecular Hepatology.2026; 32(1): e125. CrossRef
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Contemporary trends in extrahepatic mortality of chronic liver disease in the United States from 2014 to 2023 Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed Clinical and Molecular Hepatology.2026; 32(1): e24. CrossRef
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 Liver International.2026;[Epub] CrossRef
The global epidemiology of alcohol-associated liver disease Pojsakorn Danpanichkul, Francisco Idalsoaga, Frank Murray, Juan Pablo Arab, Luis Antonio Díaz Hepatology Communications.2026;[Epub] CrossRef
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Rethinking lean metabolic dysfunction-associated steatotic liver disease: Unrecognized risk in lean populations: Editorial on “Normal-weight metabolic dysfunction-associated steatotic liver disease: Reclassification, characteristics, and adverse liver out Donghee Kim, Anoushka Shenoy, Aijaz Ahmed Clinical and Molecular Hepatology.2026; 32(3): 1441. CrossRef
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Extrahepatic manifestation of metabolic dysfunction-associated steatotic liver disease Anoushka Shenoy, Aijaz Ahmed, Donghee Kim Metabolism and Target Organ Damage.2025;[Epub] CrossRef
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
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.
Citations
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Advancing policy and practice in alcohol-associated liver disease and alcohol-attributable cancer: Correspondence to the editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the Unite Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang Clinical and Molecular Hepatology.2026; 32(1): e96. CrossRef
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
Stable Nationwide Sepsis-Related Mortality Does Not Extend to Individuals with Alcohol-Associated Liver Disease Pojsakorn Danpanichkul, Kwanjit Duangsonk, Claire S. Faulkner, Supapitch Sirimangklanurak, Tulaton Sodsri, Natchaya Polpichai, Shu-Yen Chan, Yanfang Pang, Omar Y. Mousa, Donghee Kim, Suthat Liangpunsakul, Karn Wijarnpreecha Digestive Diseases and Sciences.2026; 71(6): 2165. CrossRef
Improved survival and reduced alcohol‐associated hepatitis risk with renin‐angiotensin‐aldosterone system inhibitors in alcohol‐associated liver disease Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Andrew F. Ibrahim, Primrose Tothanarungroj, Omar Al Ta'ani, Narathorn Kulthamrongsri, Kwanjit Duangsonk, Robert J. Wong, Daniel Q. Huang, Karn Wijarnpreecha, Mazen Noureddin, Suthat Liangpunsakul Alcohol, Clinical and Experimental Research.2026;[Epub] CrossRef
Spatiotemporal trends, demographic disparities, and predictions to 2040 in gastrointestinal cancer mortality in the United States Maolang He, Jingyi Zhang, Shangqi Wang, Kainan Xing, Yanxin Zhao, Jianzhen Chen, Xi Zhang, Yong Zheng, Shuxin Tian BMC Public Health.2026;[Epub] CrossRef
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History of Alcohol‐Related Cancers and ADH1B/ALDH2 Genotypes in a Large Japanese Cohort of Male Patients With Alcohol Dependence Akira Yokoyama, Tetsuji Yokoyama Cancer Medicine.2026;[Epub] CrossRef
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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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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
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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Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.
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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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One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD)―formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study’s comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals’ unique risks.
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