Mortality burden of hepatocellular carcinoma and diabetes in the United States, 1999–2023.

e16355 Background: Hepatocellular carcinoma (HCC) and diabetes mellitus are major contributors to morbidity and mortality when coexisting. We evaluated national trends in HCC- and diabetes-related mortality from 1999 to 2023 across demographic, geographic, and urbanization strata in the United States. Methods: Mortality data for individuals aged ≥45 years were obtained from the CDC WONDER database (1999–2023). Deaths with HCC and diabetes listed as underlying or contributing causes were identified. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals, stratified by sex, race/ethnicity, census region, urbanization status, and age group. Results: From 1999 to 2023, 61,358,342 deaths occurred among individuals aged ≥45 years (30,217,781 males [49.24%], 31,140,551 females [50.75%]). HCC- and diabetes-related mortality increased significantly overall (AAPC 3.90%, 95% CI 3.24–4.55; p < 0.000001). Mortality rates were substantially higher in males (AAPC 3.78%, 95% CI 3.20–4.37; p < 0.000001) than females (AAPC 3.53%, 95% CI 2.37–4.69; p < 0.000001). Significant upward trends were observed across all census regions, most prominently in the South and West. Metropolitan areas demonstrated approximately threefold higher mortality rates than non-metropolitan areas from 1999–2020. Increasing trends were observed across racial and ethnic groups, including Hispanic and non-Hispanic Black populations, with the largest absolute increases among non-Hispanic White individuals. Conclusions: Despite overall declines in cancer mortality, age-adjusted mortality related to coexisting HCC and diabetes has risen substantially in the United States over the past two decades, particularly among adults aged ≥45 years, males, and selected racial/ethnic groups. These findings highlight the need for integrated metabolic and oncologic risk management strategies and targeted public health interventions.