Trends in global early-onset liver cancer from 1990 to 2050: an analysis of the Global Burden of Disease Study 2021

Background: Early-onset liver cancer (EOLC), occurring in individuals aged 15-49, is an emerging global health challenge. This study aims to assess health inequalities in EOLC burden across regions and sexes and to inform targeted interventions. Methods: Using Global Burden of Disease (GBD) 2021 data, we analyzed global EOLC incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Analyses included Joinpoint regression, decomposition, locally estimated scatterplot smoothing (LOESS), and frontier efficiency assessment. Trends to 2050 were projected via a gender-stratified Bayesian age-period-cohort (BAPC) model. Results: Absolute EOLC burden increased globally, though age-standardized rates (ASRs) declined overall. Notably, age-standardized incidence rates (ASIRs) rose among women in high socio-demographic index (SDI) regions and among men in low-middle SDI regions. Hepatitis B virus (HBV) remained the leading cause, but alcohol, hepatitis C virus (HCV), and nonalcoholic steatohepatitis (NASH), especially in young women, showed increasing contributions. Population growth and aging drove increases in the absolute burden. Frontier analysis identified Mongolia as the lowest-performing country, while Somalia, Burundi, and Ethiopia achieved relatively efficient control. The BAPC model projects continued ASR declines by 2050, yet female ASIR is expected to rise modestly due to rising NASH. Conclusion: Despite an overall declining EOLC burden, persistent gender and regional inequities and the growing impact of metabolic risks like NASH call for precision public health approaches, including etiology-specific strategies, early screening for high-risk groups (particularly young women), and strengthened health systems in underperforming regions.