Trends and disparities in hepatitis C virus-associated hepatocellular carcinoma mortality in the United States, 1999-2023

Chronic hepatitis C virus (HCV) infection is a major driver of hepatocellular carcinoma (HCC) in the United States, where HCC incidence and mortality have doubled over the past 25 years. Despite the effectiveness of direct-acting antivirals, HCV-related HCC remains substantial, reinforcing the need for sustained surveillance and early detection. This study, adhering to STROBE guidelines, analyzed deaths related to HCV-associated HCC from 1999 to 2023 using CDC-WONDER data. Deaths were identified via ICD-10 codes (B17.1, B18.2, C22.0), with demographic categorization by place of death, age, gender, race, census region, and urbanization. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population. Joinpoint regression assessed trend changes, reporting Average Annual Percent Change (AAPCs) with 95% CIs. Statistical analyses were performed using Joinpoint software, Microsoft Excel, and CDC-WONDER mapping tools. From 1999 to 2023, 50,760 U.S. deaths were attributed to HCV-associated HCC. AAMRs increased from 0.19 in 1999 to 0.43 in 2023. Among deaths with place-of-death data, most occurred in medical facilities (38.7%) or at home (35.0%). Joinpoint analysis showed increasing mortality from 1999 to 2012, stable rates through 2016, and a decline to 2023 (AAPC 2.52%). Female AAMRs rose from 0.07 to 0.17, peaking in 2013 before declining (AAPC 2.57%). Male AAMRs increased from 0.31 to 0.73, with early surges, peaking through 2016, then declining (AAPC 3.29%). Mortality was highest in NH Whites, followed by NH Blacks. NH Whites rose until 2013, then declined (AAPC 5.00%), while NH Blacks showed early sharp increases and declined after 2016 (AAPC 4.30%). Metropolitan areas had higher AAMRs than non-metropolitan areas, with both rising until the mid-2010s followed by declines (AAPC: 4.46% and 6.03%, respectively). Across regions, AAMRs rose until the mid-2010s, driven by sharp early increases in the Northeast (32.1%) and steady growth in the Midwest, South, and West (8-10%). Mortality was highest in ages 55-64 and 65-74, both showing sharp increases from 2013 to 2017 followed by declines (AAPC −3.94%). HCV-related HCC mortality has declined since the early 2010s but remains uneven across sex, race, and geography. Males, Black individuals, and urban areas bear the highest burden. These findings underscore the need to strengthen HCV testing, antiviral treatment uptake, and timely HCC surveillance in the high-risk populations.