Abstract
BACKGROUND: Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma as defined in the Global Burden of Disease (GBD) framework, remains a major contributor to global disease burden with pronounced socioeconomic disparities. However, long-term global patterns, socioeconomic gradients, and their demographic and epidemiological drivers remain incompletely characterized. This study assessed global and regional trends in liver cancer burden using GBD 2021 data. METHODS: Liver cancer disability-adjusted life years (DALYs) were estimated for 204 countries from 1990 to 2021. Temporal trends and contributing factors were examined using Joinpoint regression, age-period-cohort analysis, decomposition analysis, and frontier analysis. RESULTS: Globally, liver cancer DALYs declined between 1990 and 2021, with an average annual percent change (AAPC) of - 0.46. Declines were observed in high SDI (AAPC - 0.42), high-middle SDI (- 0.63), middle SDI (- 0.72), and low SDI regions (- 0.80), whereas low-middle SDI countries experienced a modest increase (AAPC 0.08). Decomposition analysis showed that population growth and aging were the primary drivers of global DALY increases, while epidemiological changes accounted for most declines in high SDI regions. Risk factor-specific analyses revealed declining hepatitis B-attributable DALYs globally (AAPC - 0.79), contrasted by rising MASH-attributable DALYs (AAPC 0.60), particularly in low-middle SDI countries. Frontier analysis demonstrated substantial cross-country variability in performance at comparable socioeconomic levels. CONCLUSION: Global liver cancer burden has declined overall but remains unevenly distributed, driven by divergent demographic transitions, etiologic profiles, and socioeconomic context. These findings highlight substantial unrealized potential for burden reduction, particularly in low and low-middle SDI countries.