International and regional clinical practice guidelines (CPGs) for chronic hepatitis B (CHB) have recently been updated to incorporate evolving clinical evidence. This review compares the latest major CPGs regarding natural history classification, treatment initiation, and selection of antiviral agents, specifically focusing on updates from the Korean Association for the Study of the Liver-East Asia Liver Alliance (KASL-EALA), the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the World Health Organization (WHO). While all guidelines recognize the heterogeneous and dynamic nature of CHB, managing patients in the “grey zone” or indeterminate phase remains a major challenge. The KASL–EALA 2026 guideline introduces a novel framework based primarily on hepatitis B virus (HBV) DNA levels—independent of alanine aminotransferase criteria—eliminating the indeterminate category to better align with hepatocellular carcinoma risks and simplify treatment decision-making. In contrast, AASLD 2025, EASL 2025, and WHO 2024 retain conventional immunological phase-based classifications for natural history. For treatment indications, all four guidelines advocate broader access to antiviral therapy despite their divergent structural approaches. AASLD suggests shared decision-making, EASL emphasizes individualized risk assessment, and WHO 2024 abandons the phase-based framework for treatment decisions entirely. Understanding these key similarities and differences will help clinicians optimize patient care and inform future efforts toward global harmonization in CHB management.
Won-Mook Choi, Ji Won Han, Tae Hyung Kim, Miyoung Choi, Moon Haeng Hur, Hyo Young Lee, Han Ah Lee, Byeong Geun Song, Heechul Nam, Jeong-Ju Yoo, Chang Hun Lee, Gi-Ae Kim, Hye Won Lee, Gwang Hyeon Choi, Young Eun Chon, Yun Bin Lee, Dong Hyun Sinn, Bo Hyun Kim, In Hee Kim, on behalf of the Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2026;32(3):1029-1116. Published online June 12, 2026
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.
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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
Global burden of esophageal cancer attributable to smoking and alcohol, 1990–2021, with projections to 2040: a population-based analysis of the global burden of disease study 2021 Hui Zhou, Jiao Wu, Yuan Yin Annals of Medicine.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
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
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
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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Background/Aims Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF.
Methods We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored.
Results The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE.
Conclusions Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.
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