Trends in Incidence of Hepatocellular Carcinoma Between 2000 and 2020: A Surveillance, Epidemiology, and End Results (SEER)-Based Analysis.

Introduction Hepatocellular carcinoma (HCC) remains a significant global health concern, ranking as the third leading cause of cancer-related mortality worldwide. The risk factors for HCC include chronic hepatitis B and C, alcohol-associated liver disease, and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate trends in HCC incidence in the United States from 2000 to 2020 using the Surveillance, Epidemiology, and End Results (SEER) database, with stratification by age, sex, and race/ethnicity to identify demographic differences in temporal patterns.  Methods Incidence rates of HCC per 100,000 population (age-adjusted) from 2000 to 2020 were calculated utilizing a population-based cancer registry, SEER*Stat (version 8.4.3). HCC cases were identified by the International Classification of Diseases for Oncology, third edition (ICD-O-3) site code C22.0 and histology codes 8170-8175, including only histologically confirmed malignancies. We utilized the Joinpoint Regression Program version 5.0.1 to report time-trends expressed as annual percentage change (APC). Cases with missing age, sex, or race data were excluded from stratified analyses. Statistical significance was set at a p-value less than 0.05.  Results There were a total of 242,769 cases of HCC recorded from 2000 to 2020. Since 2015, HCC incidence has declined across all age groups, with the most significant reductions observed in individuals aged 45-54 years (APC, -8.22; p < 0.05) and 55-64 years (APC, -7.03%; p < 0.05). Among racial and ethnic groups, Black individuals experienced the most pronounced decline between 2018 and 2020 (APC, -10.64%; p < 0.05), followed by Hispanics (APC, -8.25%; p < 0.05) and Asians (APC, -8.06%; p < 0.05). With regards to sex, there was a greater decline among males (APC, -7.28%; p < 0.05) from 2018 to 2020 compared to females (APC, -2.4%; p < 0.05) from 2014 to 2020.  Conclusions These findings reflect encouraging trends likely due to improved prevention and treatment of chronic liver diseases and are consistent with declining HCC incidence observed in other high-income countries. However, reliance on histologically confirmed diagnoses may underestimate the true incidence. Persistent disparities, potentially driven by differences in access to care and socioeconomic status, indicate a need for targeted interventions addressing underlying risk factors of HCC, such as obesity, alcohol, and viral hepatitis. With continued efforts focused on prevention, early detection, and treatment, the burden of HCC will continue to decline.