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Original Article

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

Clinical and Molecular Hepatology 2025;31(3):1058-1070.
Published online: April 11, 2025

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Corresponding author : Pojsakorn Danpanichkul Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79415, USA Tel: +1-3852204590, E-mail: pojsakorndan@gmail.com
Ju Dong Yang Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA Tel: +1-310-423-6000, E-mail: judong.yang@cshs.org

These authors are co-first authors.


These authors are co-senior authors.


Editor: Do Seon Song, The Catholic University of Korea, Korea

• Received: February 12, 2025   • Revised: April 7, 2025   • Accepted: April 8, 2025

Copyright © 2025 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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  • 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.
• The burden of ALD and alcohol-attributable cancers in the United States has markedly increased from 2000 to 2021. Females experienced a disproportionately rising ALD mortality rate, while primary liver cancer and pharyngeal cancers emerged as the fastest-growing alcohol-attributable malignancies.
Graphical Abstract
Alcohol consumption is a significant risk factor for illness, disability, and death [1]. Despite evidence increasingly suggesting that the safest level of alcohol intake to minimize health risks is close to zero [2], over half of Americans consume alcohol [3]. Among the most severe consequences of alcohol use is alcohol-associated liver disease (ALD), a leading cause of cirrhosis, liver failure, and liver-related deaths globally, including in the United States (US) [4,5]. According to a report from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), alcohol was responsible for 52% of cirrhosis-related deaths in the US in 2019 [6]. The economic impact of ALD is staggering, with projections estimating that costs could reach $880 billion between 2022 and 2040 [7].
Alcohol significantly contributes to chronic liver disease, ranging from liver steatosis to cirrhosis and primary liver cancer [8]. It also increases the risk of extrahepatic cancers through multiple mechanistic pathways, including acetaldehyde production, oxidative stress induction, gut microbiome disruption, and immunosuppression [9]. These mechanisms are implicated in approximately 4% of cancer cases worldwide [10]. Despite these significant risks, public awareness of the link between alcohol consumption and cancer remains alarmingly low. For example, a 2020 Health Information National Trends Survey revealed that more than half of respondents were unaware of this connection [11]. Despite escalating trends in alcohol consumption and the substantial burden posed by ALD and alcohol-attributable cancers, comprehensive research examining the impact of these conditions on the US population remains limited [12]. Consequently, this study seeks to address this gap by analyzing temporal trends in the burden of ALD and alcoholattributable cancers in the US between 2000 and 2021. To achieve this, we utilized data and methodologies from the Global Burden of Disease (GBD) Study 2021 [13].
Data source
This investigation utilized data from the GBD Study 2021, a comprehensive project that evaluates the impact of 369 diseases and 87 risk factors across 204 countries and territories [14]. Our analysis specifically focused on ALD and alcohol-attributable cancers. To access this dataset, we employed the Global Health Data Exchange query tool, an online platform that is regularly updated through international collaboration and managed by the Institute for Health Metrics and Evaluation. This study used publicly available, de-identified data from the Global Burden of Disease Study 2021. Therefore, institutional review board approval or informed consent was not required.
Definitions and measures
This study sought to assess the burden of ALD and alcohol-related cancers, with particular emphasis on the US population. The GBD database is uniquely valuable as it is the sole resource that provides mortality data for both ALD and alcohol-attributable cancers. The general estimation methods employed in the GBD 2021 study, as well as the specific approaches for assessing ALD and alcohol-attributable cancers, have been described in detail in previous research [15-17]. Regarding ALD, the etiology of chronic liver disease from GBD 2021 was divided into five main etiologies, and we extracted cirrhosis and other chronic liver diseases from alcohol to be categorized as ALD. Incidence rates were estimated using DisMod-MR 2.1, a Bayesian disease modeling meta-regression tool that generates values such as incidence, prevalence, and remission. In certain cases, spatio-temporal Gaussian process regression models were used instead. Mortality estimates in GBD 2021 were based on International Classification of Diseases (ICD) coding, assigning each death to the underlying cause that triggered the sequence of fatal events. Causeof-death estimates were derived using the Cause of Death Ensemble model, which integrates multiple statistical models and systematically selects covariates based on out-ofsample predictive performance [18]. This approach estimates mortality by location, age, sex, and year for each cause. However, the cause-of-death database was only able to estimate overall cirrhosis and other chronic liver diseases rather than their specific causes. To address this, DisMod-MR 2.1 was used to partition cirrhosis-related mortality estimates, incorporating etiological proportion models as covariates [18]. Regarding cancer, data for this study were derived from population-based cancer registries, vital registration systems, and verbal autopsy studies. Cancer classification in the GBD 2021 study followed the ICD codes, including the ICD-10 codes C00–C96 and the ICD-9 codes 140–209. Specific ICD-10 codes for alcohol-attributable cancers were identified based on prior research [16]. For comparison, we also provided data regarding other risk factors of cancer, such as smoking, high body mass index (BMI), high fasting blood sugar, and unsafe sex, from the GBD 2021 study [19-24].
Statistical analysis
The findings of this study on the incidence, prevalence, and mortality of alcohol-related conditions are presented with 95% uncertainty intervals (UIs), which are derived from the 2.5th and 97.5th percentile values of 1,000 simulations of the posterior distribution. Age-standardized rates (ASRs) were calculated following the methodology outlined in the GBD 2021 study. To evaluate temporal trends in ASRs, the annual percent change (APC) was determined. A positive lower bound of the 95% confidence interval (CI) for APC signifies a rising trend, whereas a negative upper bound indicates a declining trend. All statistical analyses were performed using version 4.9.1.0 of the Joinpoint regression program, developed by the National Cancer Institute’s Statistical Research and Applications Branch in Bethesda, US.
The burden of alcohol-associated liver disease in the US
In 2021, the prevalence of ALD in the US was 227,730 cases, with an incidence and mortality of 28,340 new cases and 21,860 deaths, respectively (Fig. 1A1C). The agestandardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized death rate (ASDR) per 100,000 inhabitants were 44.79 (95% UI 36.94 to 53.33), 5.64 (95% UI 4.59 to 6.72), and 4.16 (95% UI 3.65 to 4.67), respectively (Fig. 1D1F). From 2000 to 2021, ALD incidence, prevalence, and mortality increased by 43%, 36%, and 79%, respectively. From 2000 to 2021, the ASPR of ALD declined (APC –0.45%, 95% CI –0.61% to –0.29%), while the ASDR increased (APC 0.81%, 95% CI 0.46% to 1.16%) (Table 1). The ASIR remained stable over this period. Sex-specific trends revealed an increase in ASIRs among females (APC 0.26%, 95% CI 0.08% to 0.44%) and a decrease among males (APC –0.29%, 95% CI –0.57% to –0.01%). The ASPR decreased in males (APC –0.73%, 95% CI –1.01% to –0.46%) but remained stable in females. ASDRs rose more sharply in females (APC 1.41%, 95% CI 1.23% to 1.58%) compared to males (APC 0.47%, 95% CI 0.00% to 0.95%) (Table 1). ASPR, ASIR, and ASDR by age group are listed in Supplementary Table 1. State-level data indicated that New Mexico had the highest ASDR, at 8.16 (95% UI 6.60 to 10.16) per 100,000 population, followed by West Virginia, Oklahoma, and Wyoming (Fig. 2). ASDRs increased in 41 out of 50 states and the District of Columbia analyzed; the largest increases were observed in West Virginia, Kentucky, and Oklahoma (Supplementary Table 2).
The burden of alcohol-attributable cancer in the US
In 2021, there were 23,210 estimated deaths (95% UI 19,770 to 26,230) from alcohol-attributable cancer in the US (Fig. 3A). The estimated ASDR was 4.08 (95% UI 3.51 to 4.61) per 100,000 inhabitants. Males had a significantly higher ASDR from alcohol-attributable cancer compared to females, with values of 6.25 (95% UI 5.37 to 7.02) and 2.21 (95% UI 1.77 to 2.67) per 100,000 inhabitants, respectively (Fig. 3B). Among the eight types of cancer analyzed, primary liver cancer had the highest number of alcohol-attributable cancer deaths in 2021, with 7,410 deaths (Fig. 3C). Primary liver cancer accounted for 32% of all alcohol-attributable cancer deaths, followed by colorectal cancer (20%), esophageal cancer (17%), breast cancer (12%), lip and oral cavity cancer (10%), other pharyngeal cancers (4%), laryngeal cancer (3%), and nasopharyngeal cancer (1%) (Table 2). The highest ASDR was also observed in primary liver cancer, with an ASDR of 1.26 per 100,000 population (95% UI 1.12 to 1.43) (Fig. 3D). From 2000 to 2021, ASDRs increased for primary liver cancer (APC 2.21%, 95% CI 1.70% to 2.73%) and other pharyngeal cancers (APC 1.35%, 95% CI 1.08% to 1.62%), while ASDRs for other alcohol-associated cancers declined or remained stable (Table 2). At the state level, the District of Columbia had the highest ASDR from alcohol-attributable cancer in 2021, with a value of 6.54 (95% UI 4.82 to 8.37), followed by New Hampshire and Maryland, with values of 4.84 (95% UI 3.53 to 6.16) and 4.66 (95% UI 3.44 to 5.91), respectively (Fig. 3E). Among the 50 states (and the District of Columbia) analyzed, 39 states exhibited an increasing trend in ASDR from alcohol-attributable cancer (Supplementary Table 3); the greatest increases were observed in Oklahoma, Tennessee, and West Virginia, whereas the largest decreases were observed in the District of Columbia, Massachusetts, and New York.
The burden of risk factor-attributable cancer in the US
In 2021, among all risk factor–attributable cancers, smok-ing accounted for the highest number of deaths (154,590), followed by high BMI (47,200), dietary risk (46,950), high fasting plasma glucose (44,050), alcohol use (23,210), and unsafe sex (7,200) (Supplementary Table 4). Similarly, ASDR was highest for smoking at 25.83 (95% UI 21.49 to 30.05) per 100,000 population, followed by dietary risks at 8.02 (95% UI 1.58 to 13.52), high BMI at 7.96 (95% UI 3.17 to 13.02), high fasting plasma glucose at 7.20 (95% UI 0.67 to 13.47), alcohol use at 4.08 (95% UI 3.51 to 4.61), and unsafe sex at 1.41 (95% UI 1.33 to 1.47). Between 2000 and 2021, the ASDRs for cancers attributable to alcohol (APC 0.41%, 95% CI 0.28% to 0.54%) and high fasting plasma glucose (APC 0.44%, 95% CI 0.24% to 0.65%) were the only ones to show an upward trend (Supplementary Table 4).
This study provides updated epidemiological trends on ALD and alcohol-attributable cancer in the US, with key findings highlighting the increasing burden of these conditions. In 2021, there were 227,730 prevalent cases, 28,340 incident cases, and 21,860 deaths from ALD. Notably, while the prevalence rate of ALD is declining, mortality rates continue to rise. Gastrointestinal cancers represented the largest proportion of alcohol-attributable cancers, with rising death rates particularly observed in liver cancer and cancers of the pharynx.
Our findings indicate that ALD crude incidence, prevalence, and death have increased over the last two decades, matching trends reported by the longest-running US alcohol survey, which showed a 34% growth in alcohol consumption from 2000 to 2020 [25]. Another contributing factor could be the growing impact of obesity, which accelerates liver disease progression [19,26,27]. However, there was a slight decline in alcohol consumption between 2008 and 2009, likely multifactorial. One possible explanation is the Great Recession, which affected the US economy and may have led to a temporary decrease in alcohol consumption, as alcohol requires purchasing power [28,29]. However, national telephone survey data suggest that heavy drinking and intoxication actually increased during the recession [30]. Another reason could be decreased medical care utilization during the economic downturn [31,32].
Regionally, our study found that some states, particularly Southern regions, have higher ALD-related mortality rates. While a study from Latin America has shown that public health policies are associated with reduced ALD mortality, 33 our findings suggest a more complex relationship. The restrictiveness of alcohol policies, measured by the Alcohol Policy Scale, shows some correlation with ALD mortality. For example, South Dakota, despite having one of the least restrictive alcohol policies, does not have the highest ALD and liver cancer mortality rates [34-36]. Additionally, there was a difference in death rates between ALD and alcohol-attributable cancer. While the ALD-related death rate was higher in southwestern states (Fig. 2), the alcohol-attributable cancer death rate (Fig. 3E) was more evenly distributed across the country. This suggests that other factors, such as metabolic risk factors and social determinants of health, may also play a significant role in ALD and cancer attributable to alcohol-related mortality [37-41].
Although males continue to carry a higher overall burden of ALD, a concerning trend observed in this study is the disproportionate rise in ALD incidence, prevalence, and mortality among females over the past two decades. This rising trend is consistent with findings from previous studies using data from the United Network for Organ Sharing, the National Inpatient Sample, and the National Health and Nutrition Examination Survey (NHANES), all of which reported increasing mortality and acute-on-chronic liver failure in females with ALD [42,43]. However, this contrasts with global trends observed in the GBD 2019 cycle, where ALD in females was found to increase at a slower rate than in males [44]. Several factors may contribute to the growing burden of ALD in females in the US. These include a narrowing gender gap in alcohol consumption, with females drinking more while males drink less or maintain their levels; an increase in alcohol use disorder (AUD) among women; and lower utilization of treatment services for AUD [45-47]. Given that women experience a faster progression of liver disease and AUD, the rising rates of ALD-related prevalence, incidence, and mortality in this group are especially concerning [48,49]. These trends highlight the need for targeted interventions for women who are increasingly at risk for ALD.
Primary liver cancer, which accounts for the highest mortality among alcohol-attributable cancers, and other pharyngeal cancers are two cancers that have seen an increasing death rate from 2000 to 2021. This alarming trend is compounded by the coronavirus disease 2019 pandemic, which has led to increased alcohol consumption and alcohol sales in some regions [50]. Chronic alcohol use of more than 80 grams per day for over ten years significantly increases the risk of developing hepatocellular carcinoma, raising the likelihood by fivefold [51]. A previous study using NHANES showed an increase in heavy alcohol use in the US. This study found an increase in advanced liver disease (indicated by high FIB-4) among heavy alcohol users, which could explain the increase in the mortality of primary liver cancer attributable to alcohol [52]. Since Asian Americans and Pacific Islanders have a higher risk of death than non-Hispanic whites, increased immigration may partly explain the rising alcohol-attributable primary liver cancer mortality [53,54]. Alcohol consumption not only heightens the risk for primary liver cancer but also accelerates the progression of other liver diseases, such as metabolic dysfunction associated with steatotic liver disease and viral hepatitis [55]. Reducing alcohol consumption is therefore crucial to lowering cancer risk and alleviating the overall liver disease burden, including the rising cases of ALD and primary liver cancer [55]. In addition to liver-related cancers, alcohol consumption is strongly associated with an elevated risk of developing extrahepatic cancers, particularly colorectal and esophageal cancers. The International Agency for Research on Cancer has consistently demonstrated the strong link between alcohol and esophageal cancer risk, further emphasizing the urgency for intervention [56]. In spite of this, there are no current recommendations for screening gastrointestinal neoplasms in individuals with hazardous drinking and AUD.
The high mortality rates associated with primary liver cancer, esophageal cancer, and other alcohol-attributable cancers highlight the need for focused public health interventions and policies aimed at reducing alcohol consumption [56]. To effectively combat the rising mortality from ALD and alcohol-related cancers, it is critical to allocate resources and investments equivalent to those targeting other major public health concerns. Recent research has underscored the importance of public health policies in addressing the prevalence of ALD and primary liver cancer [57]. An ecological study revealed a strong correlation between alcohol-related policies and the prevalence of these diseases, emphasizing the need for stronger global measures [57]. Despite variability at the state level, a substantial portion of states exhibit weak alcohol policies. Many states have considerable room for improvement, particularly in terms of strengthening policies that address excessive drinking [34].
We acknowledge some limitations. First, the GBD study could not estimate the burden of metabolic dysfunction and alcohol-related liver disease, which may contribute to the rising mortality rates [58-60]. The increasing prevalence of metabolic risk factors could play a significant role in this trend [19,58-60]. Second, the GBD database does not include alcohol-attributable mortality data for certain cancer types, such as gastric cancer. Our findings may represent a conservative estimate of alcohol’s impact. One of the key challenges in studying ALD epidemiology is the lack of definitive diagnostic biomarkers and the absence of large, population-specific datasets, in contrast to the more readily available resources for viral hepatitis [61]. In addition, GBD model could not attribute the synergistic effect of multiple risk factors [60]. Third, the GBD study lacks ethnicity data, which is a crucial factor influencing ALD and cancer outcomes [62,63]. Prior analyses show higher ALD prevalence in Hispanics, while Hispanic and Asian females have reduced liver transplant access, possibly contributing to the mortality differences [63,64]. Future studies should examine ALD and alcohol-attributable cancer with race and ethnicity data [65].
In conclusion, the prevalence, incidence, and mortality of ALD in the US have increased over the past two decades. Among alcohol-attributable cancers, primary liver cancer accounted for the highest mortality and experienced the highest rising mortality rate. Notably, 39 states reported an increase in mortality rate from alcohol-attributable cancer. These findings highlight the urgent need for public health policy interventions aimed at addressing the rising mortality from ALD and alcohol-attributable cancers, with particular emphasis on women, who have shown a concerning rise in the incidence and death rate in recent years.

Authors’ contribution

Conceptualization – Pojsakorn Danpanichkul, Karn Wijarnpreecha, Ju Dong Yang. Data curation – Pojsakorn Danpanichkul, Yanfang Pang, Tanuj Mahendru, Kwanjit Duangsonk, Primrose Tothanarungroj. Formal analysis – Pojsakorn Danpanichkul, Yanfang Pang, Kwanjit Duangsonk, Daniel Q. Huang. Investigation – Pojsakorn Danpanichkul, Luis Antonio Díaz, Mark D. Muthiah. Methodology – Pojsakorn Danpanichkul, Yanfang Pang, Luis Antonio Díaz, Mark D. Muthiah, Daniel Q. Huang. Project Administration – Pojsakorn Danpanichkul, Ju Dong Yang. Supervision – Juan Pablo Arab, Suthat Liangpunsakul, Amit G. Singal, Ju Dong Yang. Validation – Pojsakorn Danpanichkul, Primrose Tothanarungroj, Pimtawan Jatupornpakdee, Tanuj Mahendru. Visualization – Pojsakorn Danpanichkul, Tanuj Mahendru, Primrose Tothanarungroj, Pimtawan Jatupornpakdee. Writing, original draft – Pojsakorn Danpanichkul, Tanuj Mahendru, Kwanjit Duangsonk, Luis Antonio Díaz, Yanfang Pang, Won-Mook Choi. Writing, review, and editing – Karn Wijarnpreecha, Donghee Kim, Mazen Noureddin, Ju Dong Yang, Juan Pablo Arab, Luis Antonio Díaz, Suthat Liangpunsakul, Amit G. Singal. All authors have read and approved the final version of the manuscript for submission.

Acknowledgements

The figures of the map of the United States of America were created by using mapchart.net. The graphical abstract was created by using https://www.biorender.com/.

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.

Supplementary material is available at Clinical and Molecular Hepatology website (http://www.e-cmh.org).
Supplementary Table 1.
Age-standardized prevalence, incidence, and death rates in 2021 and changes from 2000 to 2021 of alcohol-associated liver disease in the United States, stratified by age group
cmh-2025-0169-Supplementary-Table-1.pdf
Supplementary Table 2.
Death, age-standardized death rate in 2000, 2021 and changes from 2000 to 2021 from alcohol-associated liver disease in the United States, stratified by states
cmh-2025-0169-Supplementary-Table-2.pdf
Supplementary Table 3.
Death, age-standardized death rate in 2000, 2021 and changes from 2000 to 2021 from alcohol-attributable cancer in the United States, stratified by states
cmh-2025-0169-Supplementary-Table-3.pdf
Supplementary Table 4.
Death, age-standardized death rate, and change from 2000 to 2021 from cancer, stratified by risk factors
cmh-2025-0169-Supplementary-Table-4.pdf
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.
cmh-2025-0169f1.jpg
Figure 2.
Age-standardized death rates per 100,000 population of alcohol-associated liver disease in the United States population in 2021, by state.
cmh-2025-0169f2.jpg
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.
cmh-2025-0169f3.jpg
cmh-2025-0169f4.jpg
Table 1.
Incidence, prevalence, death, and their age-standardized rates in 2000, 2021 and changes from 2000 to 2021 of alcohol-associated liver disease
Table 1.
Incidence Number, 2000 (95% UI) ASIR per 100,000, 2000 (95% UI) Number, 2021 (95% UI) ASIR per 100,000, 2021 (95% UI) APC 2000 to 2021 (95% CI) P-value
Overall 19,770 (16,530–23,380) 5.73 (4.76–6.72) 28,340 (23,010–33,900) 5.64 (4.59–6.72) –0.15 (–0.38 to 0.09) 0.224
By sex
 Female 5,150 (4,190–6,160) 2.79 (2.26–3.30) 7,880 (6,160–9,600) 2.96 (2.31–3.60) 0.26 (0.08–0.44) 0.005
 Male 14,630 (12,250–17,220) 8.99 (7.54–10.51) 20,460 (16,790–24,440) 8.55 (6.96–10.13) –0.29 (–0.57 to –0.01) 0.04
Prevalence ASPR per 100,000, 2000 (95% UI) ASPR per 100,000, 2021 (95% UI)
 Overall 167,600 (140,240–196,740) 48.9 (40.91–57.54) 227,730 (186,700–273,740) 44.79 (36.94–53.33) –0.45 (–0.61 to –0.29) <0.001
By sex
 Female 52,160 (42,920–62,180) 28.43 (23.35–34.01) 78,010 (60,920–95,870) 29.49 (23.09–35.98) 0.18 (–0.04 to 0.41) 0.106
 Male 115,440 (96,560–135,430) 71.5 (59.72–84.15) 149,720 (124,060–179,050) 61.52 (51.26–72.85) –0.73 (–1.01 to –0.46) <0.001
Death ASDR per 100,000, 2000 (95% UI) ASDR per 100,000, 2021 (95% UI)
 Overall 12,220 (11,190–13,290) 3.50 (3.20–3.80) 21,860 (19,140–24,650) 4.16 (3.65–4.67) 0.81 (0.46–1.16) <0.001
By sex
 Female 3,140 (2,790–3,520) 1.63 (1.44–1.82) 6,110 (5,130–7,180) 2.18 (1.84–2.57) 1.41 (1.23–1.58) <0.001
 Male 9,080 (8,340–9,810) 5.62 (5.17–6.07) 15,740 (13,960–17,570) 6.33 (5.63–7.03) 0.47 (0.00–0.95) 0.048

APC, annual percent change; ASDR, age-standardized death rates; ASIR, age-standardized incidence rates; ASPR, age-standardized prevalence rates; CI, confidence interval; UI, uncertainty interval.

Table 2.
Death, age-standardized death rates in 2000, 2021 and changes from 2000 to 2021 of alcohol-attributable cancer
Table 2.
Death, 2000 (95% UI) ASDR, 2000 (95% UI) Death, 2021 (95% UI) ASDR, 2021 (95% UI) APC, 2000 to 2021 (95% CI) P-value
Overall 13,320 (10,620–15,810) 3.72 (3.02–4.37) 23,210 (19,770–26,230) 4.08 (3.51–4.61) 0.41 (0.28–0.54) <0.001
By sex
 Female 4,380 (3,240–5,470) 2.18 (1.68–2.70) 6,650 (5,220–8,080) 2.21 (1.77–2.67) 0.03 (–0.16 to 0.23) 0.749
 Male 8,940 (7,100–10,550) 5.63 (4.45–6.66) 16,560 (14,210–18,620) 6.25 (5.37–7.02) 0.45 (0.31–0.60) <0.001
By type
 Breast 2,100 (1,380–2,970) 0.59 (0.39–0.82) 2,820 (1,890–4,000) 0.53 (0.36–0.74) –0.58 (–0.69 to –0.47) <0.001
 Colorectal 3,340 (2,250–4,440) 0.91 (0.63–1.20) 4,690 (3,580–5,850) 0.84 (0.64–1.04) –0.46 (–0.62 to –0.29) <0.001
 Esophageal 2,320 (1,500–3,220) 0.65 (0.43–0.90) 3,950 (2,660–5,220) 0.69 (0.47–0.90) 0.17 (–0.03 to 0.38) 0.102
 Laryngeal 590 (290–890) 0.17 (0.08–0.25) 750 (370–1,100) 0.13 (0.06–0.19) –1.24 (–1.49 to –0.99) <0.001
 Lip and oral cavity 1,370 (970–1,790) 0.39 (0.28–0.50) 2,240 (1,680–2,780) 0.39 (0.30–0.48) –0.06 (–0.23 to 0.11) 0.474
 Liver 2,890 (2,640–3,170) 0.80 (0.72–0.88) 7,410 (6,500–8,410) 1.26 (1.12–1.43) 2.21 (1.70–2.73) <0.001
 Nasopharyngeal 250 (180–330) 0.07 (0.05–0.10) 320 (240–400) 0.06 (0.05–0.08) –0.78 (–1.06 to –0.50) <0.001
 Other pharyngeal 470 (320–630) 0.14 (0.09–0.18) 1,040 (760–1,290) 0.19 (0.14–0.23) 1.35 (1.08–1.62) <0.001

APC, annual percent change; ASDR, age-standardized death rate; CI, confidence interval; UI, uncertainty interval.

ALD

alcohol-associated liver disease

APC

annual percent change

ASDR

age-standardized death rate

ASIR

age-standardized incidence rate

ASPR

age-standardized prevalence rate

ASR

age-standardized rate

AUD

alcohol use disorder

BMI

body mass index

CI

confidence interval

CODEm

Cause of Death Ensemble model

GBD

Global Burden of Disease

ICD

International Classification of Diseases

ICD-9

International Classification of Diseases

NHANES

metabolic dysfunction and alcohol-related liver disease

NIAAA

National Institute on Alcohol Abuse and Alcoholism

ST-GPR

spatiotemporal Gaussian process regression

UI

uncertainty interval
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Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States
Clin Mol Hepatol. 2025;31(3):1058-1070.   Published online April 11, 2025
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Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States
Clin Mol Hepatol. 2025;31(3):1058-1070.   Published online April 11, 2025
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Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States
Image Image Image Image
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. Age-standardized death rates per 100,000 population of alcohol-associated liver disease in the United States population in 2021, by state.
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.
Graphical abstract
Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States
Incidence Number, 2000 (95% UI) ASIR per 100,000, 2000 (95% UI) Number, 2021 (95% UI) ASIR per 100,000, 2021 (95% UI) APC 2000 to 2021 (95% CI) P-value
Overall 19,770 (16,530–23,380) 5.73 (4.76–6.72) 28,340 (23,010–33,900) 5.64 (4.59–6.72) –0.15 (–0.38 to 0.09) 0.224
By sex
 Female 5,150 (4,190–6,160) 2.79 (2.26–3.30) 7,880 (6,160–9,600) 2.96 (2.31–3.60) 0.26 (0.08–0.44) 0.005
 Male 14,630 (12,250–17,220) 8.99 (7.54–10.51) 20,460 (16,790–24,440) 8.55 (6.96–10.13) –0.29 (–0.57 to –0.01) 0.04
Prevalence ASPR per 100,000, 2000 (95% UI) ASPR per 100,000, 2021 (95% UI)
 Overall 167,600 (140,240–196,740) 48.9 (40.91–57.54) 227,730 (186,700–273,740) 44.79 (36.94–53.33) –0.45 (–0.61 to –0.29) <0.001
By sex
 Female 52,160 (42,920–62,180) 28.43 (23.35–34.01) 78,010 (60,920–95,870) 29.49 (23.09–35.98) 0.18 (–0.04 to 0.41) 0.106
 Male 115,440 (96,560–135,430) 71.5 (59.72–84.15) 149,720 (124,060–179,050) 61.52 (51.26–72.85) –0.73 (–1.01 to –0.46) <0.001
Death ASDR per 100,000, 2000 (95% UI) ASDR per 100,000, 2021 (95% UI)
 Overall 12,220 (11,190–13,290) 3.50 (3.20–3.80) 21,860 (19,140–24,650) 4.16 (3.65–4.67) 0.81 (0.46–1.16) <0.001
By sex
 Female 3,140 (2,790–3,520) 1.63 (1.44–1.82) 6,110 (5,130–7,180) 2.18 (1.84–2.57) 1.41 (1.23–1.58) <0.001
 Male 9,080 (8,340–9,810) 5.62 (5.17–6.07) 15,740 (13,960–17,570) 6.33 (5.63–7.03) 0.47 (0.00–0.95) 0.048
Death, 2000 (95% UI) ASDR, 2000 (95% UI) Death, 2021 (95% UI) ASDR, 2021 (95% UI) APC, 2000 to 2021 (95% CI) P-value
Overall 13,320 (10,620–15,810) 3.72 (3.02–4.37) 23,210 (19,770–26,230) 4.08 (3.51–4.61) 0.41 (0.28–0.54) <0.001
By sex
 Female 4,380 (3,240–5,470) 2.18 (1.68–2.70) 6,650 (5,220–8,080) 2.21 (1.77–2.67) 0.03 (–0.16 to 0.23) 0.749
 Male 8,940 (7,100–10,550) 5.63 (4.45–6.66) 16,560 (14,210–18,620) 6.25 (5.37–7.02) 0.45 (0.31–0.60) <0.001
By type
 Breast 2,100 (1,380–2,970) 0.59 (0.39–0.82) 2,820 (1,890–4,000) 0.53 (0.36–0.74) –0.58 (–0.69 to –0.47) <0.001
 Colorectal 3,340 (2,250–4,440) 0.91 (0.63–1.20) 4,690 (3,580–5,850) 0.84 (0.64–1.04) –0.46 (–0.62 to –0.29) <0.001
 Esophageal 2,320 (1,500–3,220) 0.65 (0.43–0.90) 3,950 (2,660–5,220) 0.69 (0.47–0.90) 0.17 (–0.03 to 0.38) 0.102
 Laryngeal 590 (290–890) 0.17 (0.08–0.25) 750 (370–1,100) 0.13 (0.06–0.19) –1.24 (–1.49 to –0.99) <0.001
 Lip and oral cavity 1,370 (970–1,790) 0.39 (0.28–0.50) 2,240 (1,680–2,780) 0.39 (0.30–0.48) –0.06 (–0.23 to 0.11) 0.474
 Liver 2,890 (2,640–3,170) 0.80 (0.72–0.88) 7,410 (6,500–8,410) 1.26 (1.12–1.43) 2.21 (1.70–2.73) <0.001
 Nasopharyngeal 250 (180–330) 0.07 (0.05–0.10) 320 (240–400) 0.06 (0.05–0.08) –0.78 (–1.06 to –0.50) <0.001
 Other pharyngeal 470 (320–630) 0.14 (0.09–0.18) 1,040 (760–1,290) 0.19 (0.14–0.23) 1.35 (1.08–1.62) <0.001
Table 1. Incidence, prevalence, death, and their age-standardized rates in 2000, 2021 and changes from 2000 to 2021 of alcohol-associated liver disease

APC, annual percent change; ASDR, age-standardized death rates; ASIR, age-standardized incidence rates; ASPR, age-standardized prevalence rates; CI, confidence interval; UI, uncertainty interval.

Table 2. Death, age-standardized death rates in 2000, 2021 and changes from 2000 to 2021 of alcohol-attributable cancer

APC, annual percent change; ASDR, age-standardized death rate; CI, confidence interval; UI, uncertainty interval.