Worldwide burden of liver cancer across childhood and adolescence, 2000-2021:-2021: a systematic analysis of the Global Burden of Disease Study 2021

Background Liver cancer is a significant fi cant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the fi rst 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we fi rst provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Methods Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Findings Globally, from 2000 to 2021 in the age 5-19 - 19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9-2689.8) - 2689.8) to 1692.9 (95% UI: 1482.0-1992.5) - 1992.5) and 2248.5 (95% UI: 2053.7-2474.9) - 2474.9) to 1516.6 (95% UI: 1322.1-1797.9), - 1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20-24 - 24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8-1609.4) - 1609.4) to 1285.1 (95% UI: 1159.2-1447.2) - 1447.2) and 1432.3 (95% UI: 1307.6-1585.7) - 1585.7) to 1195.5 (95% UI: 1066.1-1355.2), - 1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%-64.7%) - 64.7%) to 26.4% (95% UI: 14.2%-39.1%) - 39.1%) in the age 5-19 - 19 years group, and 46.6% (95% UI: 42.8%-51.5%) - 51.5%) to 36.5% (95% UI: 33.1%-40.9%) - 40.9%) in the age 20-24 - 24 years. From 2000 to 2021, in the age group of 5-19 - 19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8-6961.9) - 6961.9) to 4045.6 (95% UI: 3250-4995.8) - 4995.8) and 4059.2 (95% UI: 3494.5-4621.2) - 4621.2) to 2416 (95% UI: 1940.2-3022.5), - 3022.5), respectively. There was some variation in age-related sex-specific fi c patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. Interpretation The results of the present study are significant fi cant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old.