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. 2025 Jul;31(3):1058-1070.
doi: 10.3350/cmh.2025.0169. Epub 2025 Apr 11.

Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States

Pojsakorn Danpanichkul  1 , Yanfang Pang  2   3   4   5 , Tanuj Mahendru  6 , Primrose Tothanarungroj  7 , Luis Antonio Díaz  8   9   10 , Juan Pablo Arab  11 , Pimtawan Jatupornpakdee  7 , Mark D Muthiah  12 , Kwanjit Duangsonk  5 , Won-Mook Choi  13 , Daniel Q Huang  12 , Donghee Kim  14 , Mazen Noureddin  15 , Karn Wijarnpreecha  16   17   18 , Suthat Liangpunsakul  19   20   21 , Amit G Singal  22 , Ju Dong Yang  23
Affiliations

Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States

Pojsakorn Danpanichkul et al. Clin Mol Hepatol. 2025 Jul.

Abstract

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%).

Conclusion: 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.

Keywords: Alcohol; Chronic liver disease; Sex disparity; Steatotic liver disease.

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Conflict of interest statement

Conflicts of Interest

Suthat Liangpunsakul has served as a consultant for Durect and Surrozen. Mazen Noureddin has been on the advisory board for 89bio, Gilead Sciences, Intercept Pharmaceuticals, Pfizer, Novo Nordisk, Blade Therapeutics, EchoSens, Fractyl Health, Terns Pharmaceuticals, Siemens, and Roche Diagnostics; has received research support from Allergan, Bristol Myers Squibb, Gilead Sciences, Galmed Pharmaceuticals, Galectin Therapeutics, Genfit, Conatus Pharmaceuticals, Enanta Pharmaceuticals, Madrigal Pharmaceuticals, Novartis, Pfizer, Shire, Viking Therapeutics and Zydus Lifesciences; and is a minor shareholder or has stocks in Anaetos, Rivus Pharmaceuticals, and Viking Therapeutics. Ju Dong Yang consults for AstraZeneca, Eisai, Exact Sciences, and Fujifilm Medical Sciences. Amit G. Singal has served as a consultant or on advisory boards for Genentech, AstraZeneca, Eisai, Exelixis, Bayer, Elevar Therapeutics, Merck, Boston Scientific, Sirtex, HistoSonics, Fujifilm Medical Sciences, Exact Sciences, Roche Diagnostics, Abbott, and Glycotest Diagnostics. Mark D. Muthiah: M.D.M has served as a consultant to Roche Diagnostics, Estella, and Gilead Sciences. He has been an advisor for Lerna Biopharma. M.D.M. has received payment from speaking at Boston Scientific, Olympus Medical, Roche Diagnostics, and Astellas Pharma. M.D.M. is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Clinician Scientist-Individual Research Grant (MOH-001228) and NMRC Clinician Scientist Award (MOH-001631), as well as the National Research Foundation, Singapore (NRF) under the NMRC Open Fund – Large Collaborative Grant (MOH- 001325) and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. The other authors declare no competing interests.

Figures

Figure 1.
Figure 1.
(A) The number of incidences of alcohol-associated liver disease in the United States population from 2000 to 2021. (B) The number of prevalences of alcohol-associated liver disease in the United States population from 2000 to 2021. (C) The number of deaths from alcohol-associated liver disease in the United States population from 2000 to 2021. (D) ASIRs per 100,000 population of alcohol-associated liver disease in the United States population from 2000 to 2021. (E) ASPRs per 100,000 population for alcohol-associated liver disease in the United States population from 2000 to 2021. (F) ASDRs per 100,000 population from alcohol-associated liver disease in the United States population from 2000 and 2021. ASDR, age-standardized death rate; ASIR, age-standardized incidence rate; ASPR, age-standardized prevalence rate.
Figure 2.
Figure 2.
Age-standardized death rates per 100,000 population of alcohol-associated liver disease in the United States population in 2021, by state.
Figure 3.
Figure 3.
(A) The number of deaths from alcohol-attributable cancer in the United States population from 2000 to 2021. (B) Age-standardized death rates (ASDRs) from alcohol-attributable cancer in the United States population from 2000 to 2021, by sex. (C) The number of deaths from alcohol-attributable cancer in the United States population in 2000 and 2021, by type. (D) ASDRs from alcohol-attributable cancer in the United States population in 2000 and 2021, by type. (E) ASDRs from alcohol-attributable cancer in the United States population in 2021, by state.
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