Age-specific trends in liver cancer mortality in the United States, 1999–2023: A Joinpoint regression analysis.

e16334 Background: Liver cancer remains a leading cause of cancer-related mortality in the United States. Although overall mortality has increased over the past two decades, age-specific patterns and demographic disparities are not fully characterized. Here, we analyzed U.S. liver cancer mortality trends from 1999 to 2023, with a focus on age-related, racial and ethnic, and geographic differences. Methods: Mortality data for U.S. adults aged ≥25 years from 1999 to 2023 were obtained from the CDC WONDER database (ICD-10 codes C22.0–C22.9). Age-adjusted mortality rates (AAMRs) were standardized to the 2000 U.S. population. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) across age groups, sex, race/ethnicity, U.S. census regions, and levels of urbanization. Results: From 1999 to 2023, overall liver cancer AAMRs increased from 6.95 to 10.1 per 100,000. Marked age-specific differences were observed. Mortality among adults aged 45–54 and 55–64 years peaked in the mid-2010s and subsequently experienced significant declines through 2023 (recent APCs < −4.5% for both groups; P < 0.001). Specifically, while the overall AAPC for the 55–64 age group was +1.89%, mortality significantly reversed after 2016 (APC, −4.59%). In contrast, mortality continued to rise among older adults, including those aged 65–74 years (AAPC, +2.26%), 75–84 years (AAPC, +1.69%), and aged ≥85 years (AAPC, +1.77%) (all P < 0.001). Differences in mortality trends were also identified across racial and ethnic groups. Sustained increases were observed among Non-Hispanic White individuals (AAPC, +1.89%; P < 0.001), while Hispanic/Latino populations experienced declines after 2013 (APC, −0.67%; P = 0.003). Non-Hispanic Black individuals demonstrated a significant decrease in mortality between 2017 and 2020 (APC, −3.82%; P = 0.03). Regionally, liver cancer mortality declined in the Northeast after 2013 (APC, −0.66%; P < 0.001), whereas no significant post-peak declines were observed in the South or West. Conclusions: U.S. liver cancer mortality trends exhibit substantial heterogeneity by age, race and ethnicity, and geographic region. The recent, sharp declines among middle-aged adults (APCs < −4.5%) likely reflect the success of large-scale viral hepatitis screenings and highly effective antiviral therapies, whereas continued increases among older adults may relate to the cumulative impact of metabolic risk factors and delayed diagnosis. Persistent racial and regional disparities highlight the need for targeted, age-specific prevention and surveillance strategies.