Trends in hepatocellular carcinoma (HCC) incidence and impact of hepatitis C antiviral therapy: A population-based subgroup analysis.

519 Background: Hepatitis C is one of the most common causes of hepatocellular cancer (HCC) in the United States. Since their introduction in the last decade, direct-acting antivirals (DAAs) have transformed the treatment of hepatitis C, leading to cure rates of over 90% sustained virologic response (SVR). This study explored recent trends in HCC incidence across the U.S, assessing the impact of HCV therapy and subgroup variations by age, race/ethnicity, and sex. Methods: SEER data from 2014 to 2024 were used to identify adults diagnosed with primary HCC. Inclusion criteria required a confirmed HCC diagnosis and complete demographic information. Patients with metastatic liver cancers or missing key variables were excluded. Age-adjusted incidence rates were calculated per 100,000 person-years. Joinpoint regression was used to estimate the annual percent change (APC) in incidence over time. Subgroup analyses were performed by age group (45–54, 55–64, ≥65), race/ethnicity (White, Black, Hispanic, Asian), and sex. In addition, a real-world cohort of 1,075 patients with hepatitis C virus (HCV) infection who were treated with direct-acting antivirals (DAAs) between 2015 and 2019 was analyzed to assess 5-year post-treatment HCC incidence through 2024. Results: From 2014 to 2024, hepatocellular carcinoma (HCC) incidence declined from 11.5 to 9.4 per 100,000 in the U.S. Sub group analysis revealed, 1) by age: 45–54 years (APC –8.22%), 55–64 years (APC –7.03%); 2) by race: Black (APC –10.64%), Hispanic (APC –8.25%), Asian (APC –8.06%); 3) by sex: male (APC –7.28%), female (APC –2.4%). The sharpest drops were seen in adults aged 45–64 and among Black, Hispanic, and Asian populations. Men had a greater decline than women. While early-stage HCC decreased significantly, advanced-stage cases plateaued or slightly increased in older adults and non-Hispanic Whites. In a real-world cohort of 1,075 hepatitis C patients treated with DAAs (2015–2019), the 5-year HCC incidence was 5.9% through 2024. Highest risk was seen in patients with cirrhosis (2.31/100 PY). Cirrhosis, non-SVR, and baseline liver nodules were significant predictors of HCC. Conclusions: HCC incidence has declined, particularly among middle-aged adults and minority populations, reflecting improved HCV treatment uptake. However, disparities persist, women and older adults saw smaller declines and more advanced-stage disease. Post-SVR HCC risk remains elevated in cirrhotic patients, highlighting the need for ongoing surveillance and targeted screening strategies. Expanding early HCV treatment and addressing demographic gaps are essential to further reduce HCC burden.