Abstract
BACKGROUND: Acute hepatitis E (AHE) poses escalating risks to older adults (≥65 years), compounded by immunosenescence and comorbidities. Using Global Burden of Disease (GBD) 2021 data, this study analyzes global AHE burden, trends, and projections in aging populations. METHODS: Age-standardized rates (ASIR, ASMR, ASDR) for AHE in adults ≥ 65 years were extracted from GBD 2021 across 204 countries (1990-2021). Frontier analysis assessed gaps between observed burdens and sociodemographic index (SDI)-based theoretical minima. Age-period-cohort (APC) modeling evaluated age/period/cohort effects. Bayesian (BAPC), NORDPRED, and ARIMA models projected trends to 2050. RESULTS: Global ASIR increased by 1.5% annually (1990-2021), with ASMR and DALYs declining significantly. Middle SDI regions showed the steepest ASIR rise (net drift: 0.064%/year), while high SDI areas had volatile trends. Age effects peaked in ≥95-year-olds. Frontier analysis revealed persistent ASIR-SDI gaps, particularly in low-middle SDI regions. Projections indicate a ASIR rise by 2050 (113.04/100,000), contrasting with declining ASMR (0.056/100,000) and ASDR (1.31/100,000) and the NORDPRED, ARIMA, and EAPC models exhibit analogous global predictive trends. CONCLUSIONS: Diverging trends of rising incidence and falling mortality highlight unmet prevention needs. High-burden regions require SDI-stratified strategies, prioritizing vaccination programs (e.g., HEV 239), zoonotic transmission control, and enhanced surveillance. The Sustainable Development Goals (SDGs) envision hepatitis elimination by 2030 (Target 3.3). However, our analysis projects ongoing AHE burden in aging populations through 2050, indicating the need for post-2030 policy adaptations.