Trends in incidence rates of hepatocellular carcinoma and stage at diagnosis by demographics in the U.S. from 2004 to 2021: a joinpoint analysis of the SEER database

From 2004 to 2015, overall HCC incidence increased (APC 3.16; <i>p</i> < 0.01), followed by a significant decline from 2015 to 2021 (APC -1.24; <i>p</i> < 0.01). Racial/ethnic subgroup trends varied: Hispanics, Non-Hispanic Blacks, and American Indian/Alaska Native populations showed rising incidence until 2015 with subsequent declines, while changes among Non-Hispanic Whites were less pronounced. After 2015, incidence declined among females (APC -0.27) and males (APC -1.85). Age-specific trends showed decreasing rates among individuals aged 35-49 and 50-64 years, with declines in those 65+ beginning in 2019. Localized-stage HCC incidence decreased after 2015, while regional trends fluctuated and distant-stage incidence continued to rise. Stage-specific patterns also differed by race. HCC incidence has declined overall since 2015, potentially reflecting improved hepatitis C therapy and risk-factor management. However, persistent or rising rates in specific demographic groups and increasing distant-stage diagnoses highlight ongoing disparities and the need for enhanced screening and early detection strategies.