Dear Editor,
We commend Danpanichkul et al. [
1] for their comprehensive analysis of alcohol-associated liver disease (ALD) and cancer trends in the United States. The study highlights critical epidemiological shifts, particularly the rising burden among females and the dominance of gastrointestinal cancers. However, several methodological and translational limitations warrant discussion to strengthen the interpretation and applicability of these findings.
The study authors advocate for public health policies but fail to evaluate existing interventions or propose actionable strategies. For instance, despite noting higher ALD mortality in states with more permissive alcohol policies (e.g., New Mexico, West Virginia), the study lacks analysis of specific policy impacts, such as alcohol taxation or advertising bans. Research has shown that a 10% increase in alcohol taxes can reduce alcohol consumption by 5% to 10% and cirrhosis mortality by 8% [
2]. Similarly, Scotland's minimum unit pricing policy has reduced alcohol-related deaths by 10% [
3]. However, the study does not propose a similar policy framework for alcohol, as seen in the success of tobacco control policies. This omission limits the study's utility for policymakers. In the U.S. context, feasible strategies could include federal subsidies for alcohol screening and brief intervention programs in primary care settings, as recommended by the U.S. Preventive Services Task Force.
The Global Burden of Disease (GBD) database lacks ethnicity-specific data, which is a significant flaw given the well-documented disparities in ALD outcomes. Hispanic and Native American populations have 2 to 3 times higher ALD mortality than non-Hispanic Whites [
4], driven by genetic susceptibility, inequities in healthcare access, and socioeconomic factors. By homogenizing these groups, the study obscures opportunities for targeted interventions. For example, culturally tailored alcohol use disorder (AUD) treatment programs have been shown to reduce ALD progression in Hispanic communities [
5], but these nuances are not discussed.
While the study notes the increasing ALD mortality among women, it neglects the biological and social mechanisms driving this trend. Women exhibit higher hepatic in-flammation and faster fibrosis progression at lower alcohol doses due to hormonal differences and lower gastric alcohol dehydrogenase activity [
6]. Additionally, societal stigma delays treatment-seeking in women, as evidenced by lower AUD treatment utilization despite similar disease severity [
7]. Without addressing these sex-specific pathways, interventions will remain inadequately targeted.
Moreover, the authors rely on the GBD's Cause of Death Ensemble model (CODEm) to estimate mortality rates, but this model may have limitations in attributing alcohol-specific causes of death. For example, a validation study comparing CODEm estimates with national death certificate data in Mexico found that alcohol-related liver disease deaths were underestimated due to misclassification of ICD-10 codes [
8]. This leads to an underestimation of the true burden of alcohol-related liver cancer deaths.
In conclusion, while Danpanichkul et al. provide valuable insights into the epidemiological trends of alcohol-associated liver disease and cancer in the United States, their study has notable limitations. These include the lack of evaluation of existing public health interventions and actionable strategies, the absence of ethnicity-specific data which is crucial for targeted interventions, and the neglect of biological and social mechanisms driving the rising ALD mortality among women. Addressing these gaps would enhance the study's applicability for policymakers and improve the effectiveness of future interventions.
FOOTNOTES
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Conflicts of Interest
The author has no conflicts to disclose.
Abbreviations
alcohol-associated liver disease
Cause of Death Ensemble model
REFERENCES
- 1. 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.
- 2. van den Berg M, van Baal PH, Tariq L, Schuit AJ, de Wit GA, Hoogenveen RT. The cost-effectiveness of increasing alcohol taxes: a modelling study. BMC Med 2008;6:36.
- 3. Maharaj T, Angus C, Fitzgerald N, Allen K, Stewart S, MacHale S, et al. Impact of minimum unit pricing on alcohol-related hospital outcomes: systematic review. BMJ Open 2023;13:e065220.
- 4. Anouti A, Seif El Dahan K, Rich NE, Louissaint J, Lee WM, Lieber SR, et al. Racial and ethnic disparities in alcohol-associated liver disease in the United States: A systematic review and meta-analysis. Hepatol Commun 2024;8:e0409.
- 5. Mellinger JL, Fernandez A, Shedden K, Winder GS, Fontana RJ, Volk ML, et al. Gender disparities in alcohol use disorder treatment among privately insured patients with alcohol-associated cirrhosis. Alcohol Clin Exp Res 2019;43:334-341.
- 6. White AM. Gender differences in the epidemiology of alcohol use and related harms in the United States. Alcohol Res 2020;40:01.
- 7. Díaz LA, Arab JP, Louvet A, Bataller R, Arrese M. The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2023;20:764-783.
- 8. de Carvalho MH, Álvarez-Hernández G, Denman C, Harlow SD. Validity of underlying cause of death statistics in Hermosillo, Mexico. Salud Publica Mex 2011;53:312-319.
Citations
Citations to this article as recorded by
- Reply to correspondence 2 on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”
Dibin Liu
Clinical and Molecular Hepatology.2026; 32(2): e264. CrossRef - 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 Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang
Clinical and Molecular Hepatology.2026; 32(2): e246. CrossRef
