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Correspondence to letter to the editor on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”

Pojsakorn Danpanichkul1orcid, Luis Antonio Diaz2,3,4, Juan Pablo Arab2,3,5, Amit G. Singal6, Ju Dong Yang7orcid
Clinical and Molecular Hepatology 2026;32(2):e246-e248.
Published online: June 17, 2025

1Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

2Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

3Observatorio Multicéntrico de Enfermedades Gastrointestinales (OMEGA), Santiago, Chile

4MASLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA

5Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

6Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

7Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Corresponding author : Pojsakorn Danpanichkul Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA E-mail: pojsakorndan@gmail.com
Ju Dong Yang Medical Director of Liver Cancer Program, Associate Professor of Medicine, Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8900 Beverly Blvd, Los Angeles, CA 90048, USA Tel: +1-310-423-1971, Fax: +1-310-423-2356, E-mail: judong.yang@cshs.org

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

• Received: June 5, 2025   • Accepted: June 13, 2025

Copyright © 2026 by The Korean Association for the Study of the Liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See the reply "Reply to correspondence 2 on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”" in Volume 32 on page e264.
See the article "Letter to the editor on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”" on page e153.
  • Keywords: Alcohol; Chronic liver disease; Health disparity
    • Dear Editor,
    We are grateful to Liu [1] for thoughtful comments and critical appraisal of our manuscript [2], which aimed to provide a comprehensive assessment of sex-specific trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers using the most recent Global Burden of Disease (GBD) 2021 framework [3].
    We appreciate the suggestion to deepen our policy analysis. While our primary aim was to identify epidemiological trends in ALD and alcohol-attributable cancers, we agree that incorporating policy context enhances translational relevance. As highlighted by Liu, interventions such as alcohol taxation and minimum unit pricing have proven effective. Indeed, recent evidence from Latin America demonstrated that a higher number of alcohol-related public health policies was associated with lower ALD mortality and alcohol use disorder (AUD) prevalence [4]. Likewise, Rehm et al. [5] showed that integrated alcohol policies led to significant reductions in per capita alcohol consumption. While our study did not directly assess the impact of specific policies, we used state-level variation as a proxy to reflect differenc-es in policy implementation and enforcement [6]. The results underscore the need for coordinated national strategies that incorporate evidence-based policy tools, including excise taxes, advertising restrictions, and limitations on alcohol availability, particularly in regions with the highest burden. However, policy-level efforts alone are insufficient. Reducing alcohol-related mortality requires a multi-level approach. At the individual level, patient education can promote awareness and encourage behavior change. Provider-level strategies, such as routine alcohol screening and brief interventions [7], should be more widely adopted. At the neighborhood level, interventions targeting the density of alcohol outlets through zoning regulations can influence consumption patterns [8]. These efforts should be combined with broader policy measures to form a comprehensive public health response.
    We concur that ethnic disparities in ALD outcomes are of critical importance. As noted, the GBD framework does not currently disaggregate U.S. data by ethnicity, limiting our ability to examine intra-national disparities [3]. However, recent studies, utilizing the National Health and Nutrition Examination Survey dataset [9,10], fill this gap by demonstrating markedly different ALD trajectories across racial and ethnic groups. Notably, Hispanic individuals had disproportionately high ALD prevalence despite lower overall alcohol consumption, and Asian females had the lowest rates of liver transplantation once waitlisted [9]. These findings highlight the structural and biological contributors to ALD and AUD disparities and reinforce our call for more granular data in future GBD iterations. Policy interventions are also a key to addressing racial and ethnic disparities in alcohol mortality, often driven by unequal healthcare access, neighborhood factors, and exposure to alcohol-related harms [11,12].
    We appreciate the attention drawn to the rise in ALD among women. Our study identified steeper increases in ALD-related mortality and cancer burden among women than men, which warrants targeted interventions. The sexbased biological mechanisms underlying greater susceptibility to alcohol-induced liver injury in women include differences in alcohol metabolism, hormonal modulation of inflammation, and altered gut permeability [13]. These mechanisms, combined with sociocultural barriers to AUD treatment and care engagement, contribute to the accelerated disease progression observed in women [14]. We support efforts to develop sex-specific clinical pathways and public health messaging to address these disparities.
    We also acknowledge the limitations of CODEm and the potential for cause-of-death misclassification in alcohol-related conditions. The GBD 2021 capstone publication notes this challenge, especially in settings with underdeveloped health reporting systems [3]. However, in high-income countries like the U.S., death certificate coding is generally reliable, and K70 codes have demonstrated reasonable validity. Moreover, our findings align closely with those from national registries and independent analyses, including Zhang et al. [15], which used GBD methodology to describe similar upward trends in ALD incidence. While refinements in cause attribution will always be necessary, the consistency of our findings across multiple sources underscores the robustness of our conclusions.
    We thank Liu for their constructive engagement with our work. We believe our study offers timely insight into evolving patterns of ALD and alcohol-attributable cancer burden in the U.S., with important implications for both research and policy. Future investigations should aim to integrate policy effectiveness, ethnicity-specific risk, and sex-based biological mechanisms into a unified framework for reducing the burden of alcohol-related diseases.

    Authors’ contribution

    Writing, original draft – Pojsakorn Danpanichkul, Luis Antonio Diaz. Writing, review, and editing – Juan Pablo Arab, Ju Dong Yang, Amit G. Singal. All authors have read and approved the final version of the manuscript for submission.

    Conflicts of Interest

    Amit G. Singal has served as a consultant or on advisory boards for Genentech, AstraZeneca, Eisai, Exelixis, Bayer, Elevar, Boston Scientific, Sirtex, FujiFilm Medical Sciences, Exact Sciences, Helio Genomics, Roche, Abbott, Glycotest, Curve Bio, IMCare, and GRAIL. Ju Dong Yang consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.

    ALD

    alcohol-associated liver disease

    AUD

    alcohol use disorder

    GBD

    global burden of disease

    SLD

    steatotic liver disease
    • 1. Liu D. Letter to the editor on “Sex disparities in alcoholassociated liver disease and subtype differences in alcoholattributable cancers in the United States”. Clin Mol Hepatol 2026;32:e153-e154.
    • 2. Danpanichkul P, Pang Y, Mahendru T, Tothanarungroj P, Díaz LA, Arab JP, et al. Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States. Clin Mol Hepatol 2025;31:1058-1070.
    • 3. GBD 2021 Causes of Death Collaborators. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2024;403:2100-2132.
    • 4. Díaz LA, Idalsoaga F, Fuentes-López E, Márquez-Lomas A, Ramírez CA, Roblero JP, et al. Impact of public health policies on alcohol-associated liver disease in Latin America: An ecological multinational study. Hepatology 2021;74:2478-2490.
    • 5. Rehm J, Lange S, Miščikienė L, Jiang H. The impact of an integrated alcohol policy: The example of Lithuania. Drug Alcohol Rev 2025;44:403-410.
    • 6. Subbaraman MS, Sesline K, Kerr WC, Roberts SCM. Associations between state-level general population alcohol policies and drinking outcomes among women of reproductive age: Results from 1984 to 2020 National Alcohol Surveys. Alcohol Clin Exp Res (Hoboken) 2023;47:1773-1782.
    • 7. Saitz R. Alcohol screening and brief intervention in primary care: Absence of evidence for efficacy in people with dependence or very heavy drinking. Drug Alcohol Rev 2010;29:631-640.
    • 8. Hippensteel CL, Sadler RC, Milam AJ, Nelson V, Debra Furr-Holden C. Using zoning as a public health tool to reduce oversaturation of alcohol outlets: An examination of the effects of the new “300 Foot Rule” on packaged goods stores in a Mid-Atlantic City. Prev Sci 2019;20:833-843.
    • 9. Ayares G, Díaz LA, Fuentes-López E, Idalsoaga F, Cotter TG, Dunn W, et al. Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States. Liver Int 2024;44:2822-2833.
    • 10. Kim D, Danpanichkul P, Wijarnpreecha K, Cholankeril G, Loomba R, Ahmed A. Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023. Clin Mol Hepatol 2025;31:382-393.
    • 11. Danpanichkul P, Pang Y, Kim D, Auttapracha T, Chan SY, Kim DH, et al. Disproportionately rising mortality rates of alcoholassociated acute Pancreatitis: Analysis from centers for Disease Control and prevention database (2011-2020). Pancreatology 2025;25:508-515.
    • 12. Slutske WS, Deutsch AR, Piasecki TM. Neighborhood contextual factors, alcohol use, and alcohol problems in the United States: Evidence from a nationally representative study of young adults. Alcohol Clin Exp Res 2016;40:1010-1019.
    • 13. Bizzaro D, Becchetti C, Trapani S, Lavezzo B, Zanetto A, D’Arcangelo F, et al. Influence of sex in alcohol-related liver disease: Pre-clinical and clinical settings. United European Gastroenterol J 2023;11:218-227.
    • 14. Sedarous M, Flemming JA. Culture, stigma, and inequities creating barriers in alcohol use disorder management in alcohol-associated liver disease. Clin Liver Dis (Hoboken) 2023;21:130-133.
    • 15. Zhang X, Zhang X, Liu M, Zhu L, He Z. Global, regional, and national burden of cirrhosis and other chronic liver diseases due to alcohol use, 1990-2019: a systematic analysis for the Global Burden of Disease study 2019. BMC Gastroenterol 2022;22:484.

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    Correspondence to letter to the editor on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”
    Clin Mol Hepatol. 2026;32(2):e246-e248.   Published online June 17, 2025
    DOI: https://doi.org/10.3350/cmh.2025.0594
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    Correspondence to letter to the editor on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”
    Clin Mol Hepatol. 2026;32(2):e246-e248.   Published online June 17, 2025
    DOI: https://doi.org/10.3350/cmh.2025.0594
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