Alcohol- and Drug-Induced Mortality Trends By Sex and Race Among U.S. Decedents with Liver disease (1999-2043)

Liver disease-associated mortality in the United States has been rising, and substance-related deaths are an increasing part of this burden. We evaluated long-term national trends in alcohol- and drug-induced mortality among decedents with liver disease and assessed differences by sex and race, with projections through 2043.

We performed a retrospective, population-based analysis of U.S. death certificate data from CDC WONDER (1999-2023). Liver disease was identified when ICD-10 codes K70-K76 appeared as a multiple cause of death; rates were summarized as crude and age-adjusted mortality rates standardized to the 2000 U.S. population, stratified by sex and race (Black/African American vs. White) and by etiology group (alcohol-induced, drug-induced, other causes). Temporal changes were assessed using joinpoint regression, and time-series forecasting was used to project age-adjusted rates through 2043.

From 1999 to 2023, there were 2,255,627 liver disease-associated deaths, including 483,457 alcohol-induced, 29,742 drug-induced, and 1,742,428 from other causes. Age-adjusted mortality increased across all categories over the study period (drug-induced 0.354→0.605 per 100,000; alcohol-induced 5.972→9.678; other causes 25.478→28.193). Joinpoint analyses showed shared inflection points in 2018 and 2021, with the steepest increases from 2018 to 2021 (APC + 14.07% drug-induced, + 12.88% alcohol-induced, + 7.38% other causes), followed by post-2021 declines in alcohol-induced and other-cause mortality. Mortality remained higher in men, but alcohol-induced mortality rose faster in women overall (AAPC 3.19% vs. 1.48% in men). By race, alcohol-induced mortality increased steadily among White individuals (AAPC 2.55), while Black/African American individuals showed sharper swings, including a marked rise from 2018 to 2021 (APC + 15.44%) followed by a pronounced decline. Forecasting suggested continued growth through 2043, reaching approximately 0.85 (drug-induced), 12.5 (alcohol-induced), and 32.5 (other causes) deaths per 100,000.

Liver disease-associated mortality increased from 1999 to 2023 across alcohol-induced, drug-induced, and other causes, with synchronized shifts around 2018 and 2021 and persistent disparities by sex and race. Projections indicate that mortality will likely continue to rise through 2043, supporting the need for integrated liver disease and substance-use prevention strategies with targeted efforts for high-risk subgroups.