Epidemiological trends and burden of liver cancer mortality due to hepatitis B in South Asia: A retrospective analysis from 1990 to 2023 with advanced machine learning forecasting to 2050.

e16209 Background: Hepatitis B virus (HBV) remains a major driver of liver cancer mortality in South Asia. Despite the availability of effective vaccination and antiviral therapies, the long-term regional and country-specific mortality trends attributable to HBV remain inadequately characterized. We aimed to evaluate temporal trends and forecast future mortality burden across South Asia. Methods: We conducted a retrospective population-based analysis of age-standardized mortality rates (ASMRs) for liver cancer attributable to hepatitis B from 1990 to 2023 across South Asia, using the Global Burden of Disease 2023 database, stratified by country and sex. Temporal trends were quantified using estimated annual percentage change (EAPC) with 95% confidence intervals (CIs). Advanced machine-learning–based time-series models were applied to forecast ASMRs through 2050, with uncertainty assessed using prediction intervals. Results: From 1990 to 2023, liver cancer mortality attributable to hepatitis B demonstrated a significant increasing trend in South Asia overall (both sexes EAPC 0.46; 95% CI 0.27–0.65). Rising trends were observed in both females (EAPC 0.58; 95% CI 0.41–0.75) and males (EAPC 0.56; 95% CI 0.35–0.77), with consistently higher ASMRs among males. Country-specific analyses revealed the steepest increases in Pakistan (both sexes EAPC 0.55), Nepal (0.54), and India (0.46). Bangladesh showed a divergent pattern, with increasing mortality among males (EAPC 0.21; 95% CI 0.05–0.37), while female mortality remained relatively stable (EAPC −0.13; 95% CI −0.45 to 0.19). Bhutan exhibited modest and largely non-significant changes across sexes. Forecasting models project persistently elevated or rising ASMRs through 2050, particularly among males. Bangladesh and Bhutan are projected to maintain high male mortality burdens, while South Asia overall demonstrates widening prediction intervals beyond 2035. Conclusions: Liver cancer mortality attributable to hepatitis B is increasing across South Asia, with pronounced sex and country-level heterogeneity. Rising trends among males, particularly in Bangladesh, India, Pakistan, and Nepal, underscore critical gaps in HBV prevention, diagnosis, and long-term antiviral coverage. Location Sex EAPC Lower 95%CI Upper 95%CI Bangladesh Both 0.02 -0.19 0.22 Bangladesh Female -0.13 -0.45 0.19 Bangladesh Male 0.21 0.05 0.37 Bhutan Both 0.07 -0.22 0.37 Bhutan Female 0.20 -0.09 0.49 Bhutan Male 0.02 -0.26 0.31 India Both 0.46 0.26 0.66 India Female 0.58 0.38 0.78 India Male 0.56 0.35 0.78 Nepal Both 0.54 0.26 0.82 Nepal Female 0.14 -0.09 0.37 Nepal Male 0.81 0.53 1.10 Pakistan Both 0.55 0.41 0.69 Pakistan <jats:td colspan="1"