Global, regional, and national burden of liver cancer due to non-alcoholic steatohepatitis and non-alcoholic fatty liver disease, 1990-2021: a multi-model trend analysis and forecasting study.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), significantly contribute to the increasing incidence of liver cancer due to NASH (NALC), emphasizing the urgent need to address the associated global health burden.

Methods: Using the Global Burden of Disease 2021 dataset, we analyzed the incidence, mortality, and disability-adjusted life year (DALY) rates of NALC and NAFLD from 1990 to 2021 across 204 countries. The Joinpoint model, age-period-cohort modeling, decomposition analysis, and frontier analysis were used to assess trends, identify contributing factors, and evaluate health inequities. Projections for future incidence were made using Nordpred and Bayesian age-period-cohort models.

Results: The global incidence and mortality rates of NALC have increased significantly. Incidence rose from 14,413.92 cases (95% CI 11,470.95-17,854.24) in 1990 to 42,291.37 (95% CI 34,032.64-51,129.45) in 2021. This trend was particularly evident in low-middle SDI countries, while high SDI countries exhibited declining mortality rates despite rising incidence. Population growth was a primary driver of the increased burden in most regions. Projections suggest that NALC incidence may reach 43,525.53 (95% CI 14,169.28-72,881.77) by 2039, particularly among the elderly, highlighting the serious future risks associated with NALC globally.

Conclusion: The findings highlight the growing global burden of NALC driven by NAFLD, especially in low- to middle-income regions. Targeted interventions, alongside a deeper understanding and better resource allocation, are essential to mitigate the rising incidence and address the health disparities associated with this expanding public health challenge.