Mortality trends of comorbid viral hepatitis C and psychoactive substance use disorders in the United States: Insights from CDC WONDER, 1999–2023

Viral hepatitis C (HCV) remains a major global health challenge, and psychoactive substance use disorders (SUD) significantly compound its burden. However, national mortality trends from comorbid HCV and psychoactive SUD are not well characterized. This study aimed to examine temporal, demographic, and regional patterns in mortality associated with comorbid HCV and psychoactive SUD in the United States. A descriptive analysis of CDC WONDER death certificate data from 1999-2023 was performed. Deaths were identified using International Statistical Classification of Diseases and Health Related Problems - 10th revision codes B17.1 and B18.2 for HCV and F10-F19 for psychoactive SUD. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) with 95% confidence intervals were calculated and stratified by sex, age, race/ethnicity, U.S. geographic region, and urban-rural status. A total of 80,403 deaths occurred between 1999 and 2023. Mortality rose in 1999-2003 (APC + 16.0), declined in 2003-2009 (-2.2), increased again in 2009-2014 (+8.6), and fell after 2020 (-8.9). Males consistently had higher AAMRs, peaking at 1.6 in 2016 vs 0.6 in females. The steepest rise occurred in ages 55-74 years, while younger adults (25-44) increased after 2012. Non-Hispanic American Indians/Alaska Natives had the highest AAMRs (2.0), followed by non-Hispanic Blacks (1.2). The West and South had the greatest burden, with Colorado, Louisiana, Montana, Oklahoma, Oregon, and DC in the highest mortality decile. Rural mortality exceeded urban mortality. Comorbid HCV and psychoactive substance use disorder mortality has fluctuated over time, showing recent declines but persistent disparities by sex, race/ethnicity, and geography. Integrated prevention and treatment approaches remain urgently needed.