IMPORTANCE Alcohol-associated liver disease (ALD) is a major public health concern, accounting for one-quarter of cirrhosis-related deaths and becoming the leading indication for liver transplantation in the US, with concerning increases in mortality during and following the COVID-19 pandemic onset.

OBJECTIVE To evaluate comprehensive national trends in ALD mortality in the US from 1999 to 2022, with a particular focus on disparities related to sex, race, ethnicity, and age.

DESIGN, SETTING, AND PARTICIPANTS This retrospective cross-sectional analysis used the Centers for Disease Control and Prevention Wide Ranging Online Data for Epidemiologic Research mortality database from 1999 to 2022, examining death certificates across all 50 states and the District of Columbia. The study included individuals aged 25 years and older. Data analysis was performed from September to November 2024.

EXPOSURE ALD mortality was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (K70.xx) for both alcohol-associated hepatitis (K70.1x) and alcohol-associated cirrhosis (K70.3x).

MAIN OUTCOMES AND MEASURES Primary outcomes included age-adjusted annual mortality rates per 100 000 population, stratified by sex, age groups (25-44, 45-64, 65-84, and ≥85 years), race and ethnicity, and geographic regions. Joinpoint regression analysis was used to calculate average annual percentage changes (AAPCs) and to identify significant trend changes.

RESULTS In this study, a total of 436 814 ALD deaths were recorded (308 923 men [70.7%]), with ALD mortality increasing from 6.71 to 12.53 deaths per 100 000 between 1999 and 2022 and significant acceleration during 2018 to 2022 (annual percentage change [APC], 8.94%; 95% CI, 6.27% to 14.51%; P = .001). Women showed more rapid increases than men (AAPC, 4.29% [95% CI, 3.09% to 5.51%] vs 2.50% [95% CI, 1.51% to 3.51%]), whereas young adults (aged 25-44 years) demonstrated concerning trends (AAPC, 4.23%; 95% CI, 3.47% to 4.83%; P = .001). American Indian and Alaska Native populations experienced the highest mortality rates, increasing from 25.21 to 46.75 deaths per 100 000 (AAPC, 4.93%; 95% CI, 3.45% to 5.96%; P = .001). Alcohol-associated hepatitis mortality increased from 0.47 to 0.76 deaths per 100 000 (AAPC, 2.08%; 95% CI, 1.27% to 3.05%; P = .001), with women showing steeper increases than men (AAPC, 3.94% [95% CI, 2.58% to 5.46%] vs 1.56% [95% CI, 0.73% to 2.42%]). Alcohol-associated cirrhosis mortality increased from 4.09 to 9.52 deaths per 100 000 (AAPC, 4.00%; 95% CI, 3.63% to 4.40%; P = .001), with particularly concerning trends among women (APC from 2011 to 2022, 8.32%; 95% CI, 7.40% to 9.82%; P = .01) and adults aged 25 to 44 years (APC from 2018 to 2022, 19.51%; 95% CI, 15.00% to 28.53%; P = .001).

CONCLUSIONS AND RELEVANCE In this cross-sectional study using data from the Centers for Disease Control and Prevention Wide Ranging Online Data for Epidemiologic Research database, ALD mortality increased significantly across demographic groups, with particularly concerning trends among women, younger adults, and American Indian and Alaska Native populations. These findings highlight the urgent need for targeted public health interventions and enhanced surveillance, especially given the sustained impact of COVID-19 pandemic-related changes in alcohol consumption patterns.