Global burden and international disparities in NASH-associated liver Cancer: mortality trends (1990-2021) and future projections to 2045.

Background: NASH-associated liver cancer (NALC) is a significant contributor to global cancer mortality, closely linked to the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). This study comprehensively examines the global burden of NALC from 1990 to 2021. Methods: This study used data from the Global Burden of Disease (GBD) 2021 database to analyze NALC death and age-standardized death rates (ASDR) globally and regionally from 1990 to 2021. We applied Joinpoint regression analysis to assess temporal trends, calculating the annual percent change (APC) and average annual percent change (AAPC). Decomposition analysis was performed to break down mortality changes into contributions from population aging, growth, and epidemiological changes. A frontier analysis was used to evaluate the relationship between NALC burden and sociodemographic development using the Socio-Demographic Index (SDI). Prediction analysis of NALC deaths and ASDR from 2021 to 2045 were estimated using the Nordpred model. Results: From 1990 to 2021, the global burden of NALC deaths increased significantly, with the ASDR rising from 0.38 per 100,000 in 1990 to 0.48 per 100,000 in 2021. Age-specific data in 2021 revealed that NALC deaths peaked in the 65-69 age group for men and 70-74 age group for women. Decomposition analysis indicated that population growth was the most significant contributor to the global NALC death toll, followed by population aging and epidemiological changes. Frontier analysis showed that countries like Mongolia and Gambia were farthest from the disease burden frontier, while Morocco and Ukraine were closest. Prediction analysis suggest a significant increase in NALC deaths by 2045 compared to 2021, with a larger rise in deaths among women. Conclusion: Through this study, a data-driven approach is provided to reduce the global disease burden of NALC. Essential data support for public health prevention strategies is offered, helping guide the development of targeted government interventions. Trends across global regions, countries, age groups, and genders have been analyzed, providing valuable insights for the formulation of evidence-based policies aimed at mitigating the impact of NALC worldwide.