Rising Incidence of Early-Onset Liver Cancer and Intrahepatic Bile Duct Cancer: Analysis of the National Childhood Cancer Registry Database

<b>Background/Objectives</b>: Early-onset cancer is an emerging global health concern, including in the United States. However, data on early-onset liver and intrahepatic bile duct cancer remain limited. This study aims to fill this gap by analyzing trends in early-onset liver and intrahepatic bile duct cancer in the United States over the past two decades. <b>Methods</b>: This study used National Childhood Cancer Registry data to examine temporal trends in early-onset liver and intrahepatic bile duct cancer in the United States. The analysis involved estimating age-adjusted incidence rates of early-onset liver and intrahepatic bile duct cancer, stratified by histological type, ethnicity, and sex. <b>Results:</b> In 2021, the age-adjusted incidence rate of early-onset liver and intrahepatic bile duct cancer was estimated at 0.53 per 100,000 population (95% Confidence Interval [CI]: 0.48-0.59). From 2001 to 2021, the age-adjusted incidence rate showed a significant annual percent change (APC) of 1.35% (95% CI: 0.87-1.83%). When stratified by sex, the age-adjusted incidence rate in females increased significantly (APC: 3.07%, 95% CI: 2.26-3.87%) while remaining stable in males. Among racial and ethnic groups, non-Hispanic American Indian and Alaska Native (AIAN) individuals had the highest age-adjusted incidence rate, recorded at 2.67 per 100,000 population (95% CI: 0.95-5.85). By histological type, hepatic carcinoma had the highest age-adjusted incidence rate, significantly increasing over time (APC: 1.47%, 95% CI: 0.96-1.99%). In contrast, the incidence rates for hepatoblastoma and unspecified hepatic tumors remained stable between 2001 and 2021. <b>Conclusions</b>: Our study identified an increasing incidence of early-onset liver and intrahepatic bile duct cancer in the United States, primarily driven by cases in females and hepatic carcinoma.