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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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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Burden and Health System Challenges in MASLD Across East and Southeast Asia: A Narrative Review Jonathan Jaime G. Guerrero, Paolo C. Encarnacion, Wan‐Yu Wang, Shu‐Fen Liao, Ching‐Wen Chang Health Science Reports.2026;[Epub] CrossRef
Integrated bioinformatics analysis and experimental validation of SRF as a potential senescence biomarker in MASLD Mengyue Li, Chang Gao, Yuhui Shi, Wenyu Peng, Yuan Yin, Bin Lu, Zhang Fu Frontiers in Molecular Biosciences.2026;[Epub] CrossRef
Multicenter Prospective Cohort Study on Clinical Outcomes and Fibrosis Patterns in Biopsy-Proven Steatotic Liver Disease Subtypes Gi-Ae Kim, Heejoon Jang, Moon Young Kim, Jeong Hwan Park, Jung Gil Park, Eun-Young Cho, Jae Yoon Jeong, Seogsong Jeong, Seul Ki Han, Heesu Kwon, Youngae Jung, Geum-Sook Hwang, Yu Rim Lee, Soo Young Park, Sang Gyune Kim, Won Kim Gastroenterology.2026; 170(7): 1571. CrossRef
Outcomes of liver and cardiovascular metabolic diseases among lean vs non-lean individuals with metabolic dysfunction-associated steatotic liver disease Mexan Mapouka, Evariste Pabingui, Nkengeh N Tazinkeng, Milkessa Gurmessa, Ulrich Vickos, Nkafu Bechem Ndemazie, Serge Magloire Camengo Police World Journal of Gastroenterology.2026;[Epub] CrossRef
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Predictive value of TyG-BMI, CTI, and SII in identifying metabolic dysfunction-associated steatotic liver disease among patients with type 2 diabetes mellitus Yue Chen, Yayu Lai, Qu Xiang, Li Fan, Xingyu Chen, Jin Gao, Qingfeng Cheng, Xu Luo Frontiers in Nutrition.2026;[Epub] CrossRef
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Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Clinical Profile, Phenotypes, and Risk Stratification. A Narrative Review Zalina Yuryevna Sozaeva, Marina Vsevolodovna Atayeva, Elizaveta Olegovna Salatova, Irina Kazbekovna Alikova, Alexandra Evgenievna Dolgaya, Amin Gasaevich Magomedov, Kamilla Ramisovna Hafsi, Nur-Mukhamed Aslanovich Shomakhov, Elena Mukhadinovna Pshukova, Y Journal of Biochemical Technology.2026; 17(2): 30. CrossRef
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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 Clinical and Translational Gastroenterology.2026; 17(7): e01042. CrossRef
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Cryptogenic steatotic liver disease: a lean phenotype associated with increased liver-related mortality Eileen Laurel Yoon, Hyo Young Lee, Jonghyun Lee, Joo Hyun Oh, Inseok Hwang, Chan Hee Park, Sejung Kim, Huiyul Park, Ae Jeong Jo, Dae Won Jun Gut.2026; : gutjnl-2026-339142. CrossRef
Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017–2020 Study Linwan Li, Xiang’an Zhao Metabolic Syndrome and Related Disorders.2026; 24(8): 383. CrossRef
Metabolic dysfunction-associated steatotic liver disease (MASLD) is under-recognised: Should hepatic elastography be integrated into early risk stratification for people with type 2 diabetes? Aftab Ala, Ponnusamy Saravanan Clinical Medicine.2026; 26(4): 100629. CrossRef
Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic live Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice Clinical and Molecular Hepatology.2026; 32(3): e447. CrossRef
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The lean phenotype in metabolic dysfunction-associated steatotic liver disease: diagnostic challenges and prognostic implications: Correspondence to editorial on “Normal-weight metabolic dysfunction-associated steatotic liver disease: reclassification, ch Sherlot Juan Song, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Dae Won Jun Clinical and Molecular Hepatology.2026; 32(3): e389. CrossRef
Cryptogenic steatotic liver disease reveals hidden liver risk in metabolically silent lean individuals Pojsakorn Danpanichkul, Ju Dong Yang Gut.2026; : gutjnl-2026-339978. CrossRef
Red Cell Distribution Width as an Independent Prognostic Biomarker in MASLD Tom Ryu, Jaejun Lee, Ji Won Han, Hyun Yang, Keungmo Yang Antioxidants.2026; 15(9): 1065. CrossRef
Global landscape of clinical trials and therapeutic targets in metabolic dysfunction-associated steatotic liver disease: an integrative multi-omics analysis Yanxi Mu, Weixiong Zhu, Zhihao Wei, Zhao Guo, Haofei Chen, Yusheng Cheng, Wence Zhou Journal of Endocrinological Investigation.2026;[Epub] CrossRef
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Current Burden of Lean Metabolic Dysfunction‐Associated Steatotic Liver Disease Among US Adults, 2017–2023 Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed Alimentary Pharmacology & Therapeutics.2025; 61(5): 891. CrossRef
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Increased Mortality Among Lean Versus Non‐Lean Adults With MASLD: A Multicenter Study Leith Ghani, Majd B. Aboona, Claire S. Faulkner, Pooja Rangan, Moises Nevah Rubin, Ma Ai Thanda Han, Michael B. Fallon, Vincent L. Chen, Karn Wijarnpreecha Journal of Gastroenterology and Hepatology.2025; 40(8): 1919. CrossRef
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Meta‐Analysis: Effects of Steatotic Liver Disease‐Associated Genetic Risk Alleles on Longitudinal Outcomes Matthew Kubina, Vitchapong Prasitsumrit, Jarell Tan, Joo Wei Ethan Quek, Dhiraj Peddu, Ankit Mishra, Pojsakorn Danpanichkul, Jake P. Mann, Eric Trépo, Stephan Buch, Daniel Q. Huang, Cheng Han Ng, Mark D. Muthiah, Yu Jun Wong, Karn Wijarnpreecha, Vincent L Alimentary Pharmacology & Therapeutics.2025; 62(3): 244. CrossRef
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Current burden of MASLD, MetALD, and hepatic fibrosis among US adults with prediabetes and diabetes, 2017–2023 Donghee Kim, Rohit Loomba, Aijaz Ahmed Clinical and Molecular Hepatology.2025; 31(3): e235. CrossRef
Predicting the risk of lean non-alcoholic fatty liver disease based on interpretable machine models in a Chinese T2DM population Shixue Bao, Qiankai Jin, Tieqiao Wang, Yushan Mao, Guoqing Huang Frontiers in Endocrinology.2025;[Epub] CrossRef
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Paradoxical association between steatotic liver disease and favorable hepatic outcomes in HCV patients with SVRs Ming-Ling Chang, Jur-Shan Cheng, Jennifer Tai, Wei-Ting Chen, Sien-Sing Yang, Cheng-Hsun Chiu, Rong-Nan Chien, Chia-Lin Hsu, Shang-Jung Wu, Cathy SJ Fann Hepatology International.2025; 19(6): 1347. CrossRef
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Increasing Prevalence of Steatotic Liver Disease in a Japanese Health Checkup Population, 2004–2022 Yuki Nakahata, Takao Miwa, Akihiro Obora, Takao Kojima, Nobuaki Yagi, Masahito Shimizu Liver International.2025;[Epub] CrossRef
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Poor Sensitivity of the Fatty Liver Index Among Lean Individuals Mohammed Rifat Shaik, Yaron Rotman American Journal of Gastroenterology.2025;[Epub] CrossRef
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