Dear Editor,
The elegant analysis by Danpanichkul et al. in
Clinical and Molecular Hepatology showed that from 2000 to 2021 the age‑standardised death rate (ASDR) of alcohol‑associated liver disease (ALD) in the United States rose by 79%, with a steeper slope in women than in men [
1]. Whether this sex gap will persist—and to what extent future trends are shaped by demography versus changing age‑specific risk—has not been explored. We therefore used Global Burden of Disease (GBD 2021) data to project incidence and prevalence of alcohol‑related cirrhosis to 2040 and to disentangle the relative contributions of population ageing, population growth, and epidemiologic change.
GBD 2021 estimates for cirrhosis due to alcohol were downloaded from the Global Health Data Exchange [
2]. We fitted Bayesian age–period–cohort (BAPC) models separately for males, females, and both sexes combined, using 1990–2021 data as training input and assuming random‑walk priors on period and cohort effects. Posterior predictive distributions yielded age‑standardised incidence and prevalence for each year through 2040. We then applied Das Gupta’s [
3] three‑component decomposition to quantify the relative contributions of (i) population ageing, (ii) population size, and (iii) epidemiologic change (i.e., variation in age‑specific rates independent of demography) to the absolute difference between 1990 and 2021. Uncertainty intervals (UIs) represent the 2.5th–97.5th percentiles of 2,000 posterior draws.
Prevalence accelerated for both sexes but far faster for women (AAPC +6.3%) than for men (+3.3%). By 2040 the projected point estimates reach 113.3 per 100,000 (men) and 94.1 per 100,000 (women), reflecting relative increases of 84% and 219%, respectively(
Supplementary Table 2,
Supplementary Fig. 1B).
Figure 1 summarises component contributions (Decomposition of changes in alcohol related cirrhosis deaths due to population growth, population ageing and epidemiologic change rate in United States, 1990–2021). See
Supplementary Table 3 for detailed data.
Deaths: additional 10,650 deaths (both sexes) are anticipated; 85% stem from demography and 15% from adverse epidemiologic drift. Among women, epidemiologic deterioration explains 35% of excess deaths.
Disability-adjusted life-years (DALYs): net increase of 281,917 DALYs, 90% attributable to demography; epidemiologic change offsets 7% in men but adds 36% in women.
Incidence: ageing and growth account for virtually all of the male increment but only 87% in females, where epidemiology contributes a further 13%.
Prevalence: in men, demographic factors are opposed by a large negative epidemiologic term (–78%), whereas in women the epidemiologic term is positive (+9%).
Our projections extend the worrisome female‑predominant rise in ALD documented by Danpanichkul et al. into the next two decades. Incidence in men appears to have reached a plateau, but the steep, demography‑independent ascent in women signals an emerging convergence of sex‑specific burdens. Sociobehavioural data—showing faster increases in high‑risk drinking among US women—align with the positive epidemiologic component we observed for female deaths, DALYs and incidence [
4-
6].
That demography alone would enlarge the absolute ALD burden even under stable age‑specific rates underscores the indispensability of primordial prevention: curbing harmful alcohol use before liver injury becomes entrenched. Yet the sizeable, sex‑specific epidemiologic contributions highlight additional levers—earlier detection of advanced fibrosis, universal hepatitis vaccination, and equitable access to pharmacologic treatment of alcohol‑use disorder—that can bend the female trajectory.
Our study inherits the limitations of the GBD modelling cascade (e.g., misclassification of underlying cause) and the wide UIs arising from long‑range forecasting. Nevertheless, sensitivity analyses using alternative priors yielded qualitatively similar sex patterns.
Without intensified, gender‑responsive interventions, the United States will face a tripling of alcohol‑related cirrhosis prevalence by 2040, driven predominantly by women, while deaths and DALYs will continue to grow primarily because the population is older and larger. Policies that reduce alcohol exposure across the life‑course, coupled with scaled‑up screening and treatment programmes targeted to women, are urgently needed to avert the impending surge.
FOOTNOTES
-
Authors’ contributions
Kui Wang (KW): Formulated the research question, retrieved and cleaned the GBD 2021 cirrhosis data, implemented all statistical analyses and the Das Gupta decomposition in R (version 4.4.0), produced the figures and supplementary tables, and drafted the initial manuscript. Yunqing Zeng (YZ, corresponding author): Provided overall study conception and methodological oversight, independently verified the R code and results, contextualised the findings from clinical and public-health perspectives, critically revised the manuscript for substantive intellectual content, and secured the resources required to complete the project. Both authors read and approved the final manuscript and agree to be accountable for all aspects of the work.
-
Data availability
All data analysed in the present study are publicly available from the Global Burden of Disease 2021 repository (Institute for Health Metrics and Evaluation). The full dataset can be accessed and downloaded at https://ghdx.healthdata.org/gbd-2021.
-
Conflicts of Interest
The authors have no conflicts to disclose.
SUPPLEMENTARY MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (
http://www.e-cmh.org).
Supplementary Figure 1.
(A) Overall (sex-combined) age-standardised incidence rates (ASIR) per 100,000 population in the United States, 1990–2040, estimated with a Bayesian age–period–cohort model. (B) Overall (sex-combined) age-standardised prevalence rates (ASPR) per 100,000 population in the United States, 1990–2040, estimated with a Bayesian age–period–cohort model.
Supplementary Table 1.
Age‑standardised incidence rates (ASIRs) of alcohol‑related cirrhosis per 100,000 population in the United States, 1990–2040, projected with a Bayesian age–period–cohort model
Supplementary Table 2.
Age‑standardised prevalence rates (ASPR) of alcohol‑related cirrhosis per 100,000 population in the United States, 1990–2040, projected with a Bayesian age–period–cohort model
Supplementary Table 3.
Decomposition of temporal changes in the burden of alcohol-related cirrhosis in the United States, 1990–2021, attributing observed differences to population growth, population ageing, and epidemiologic shifts
Figure 1.Decomposition of changes in alcohol related cirrhosis deaths due to population growth, population ageing and epidemiologic change rate in United States, 1990–2021.
Abbreviations
average annual percent change
alcohol‑associated liver disease
age-standardised death rate
Bayesian age–period–cohort
disability-adjusted life-years
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. GBD 2021 US Burden of Disease and Forecasting Collaborators. Burden of disease scenarios by state in the USA, 2022-50: a forecasting analysis for the Global Burden of Disease Study 2021. Lancet 2024;404:2341-2370.
- 3. Song X, Zhou B, Baird S, Lu C, Song Z, Zhang Y, et al. Trends and predictions to 2030 in demographic structures and metabolic health for children and adolescents in China: analysis of national school health surveys from 2000 to 2019. Lancet Child Adolesc Health 2025;9:530-543.
- 4. Probst C, Zhu Y, Kilian C, Kerr W, Rehm J. Educational attainment as a potential effect modifier of alcohol use and 100% alcohol-attributable mortality in the United States-A longitudinal analysis of mortality linked survey data from 1997 to 2018. Addiction 2025;120:1143-1155.
- 5. Li X, Hur J, Smith-Warner SA, Song M, Liang L, Mukamal KJ, et al. Alcohol intake, drinking pattern, and risk of type 2 diabetes in three prospective cohorts of U.S. women and men. Diabetes Care 2025;48:1189-1197.
- 6. Matarazzo A, Hennekens CH, Dunn J, Benson K, Willett Y, Levine RS, et al. New clinical and public health challenges: Increasing trends in United States alcohol related mortality. Am J Med 2025;138:477-486.
Citations
Citations to this article as recorded by
- Evaluation methods of hepatic steatosis: From conventional techniques to emerging biomarkers
Kengo Moriyama
World Journal of Hepatology.2026;[Epub] 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(3): e399. CrossRef - Divergent trajectories of inflammatory bowel disease in East, South, South-East and Central Asia: A comprehensive GBD 2021 analysis
Kui Wang, Yunqing Zeng, Shanshan Zhang, Yanqing Li
Journal of Translational Autoimmunity.2025; 11: 100325. CrossRef
