Live zoster vaccination and hepatobiliary risk reduction: a nationwide South Korean study

Background/Aims: Herpes zoster (HZ) vaccination is primarily administered to prevent shingles, yet its systemic immunomodulatory effects may offer protection against other organ-related diseases, including hepatobiliary and pancreatic diseases. Therefore, this emulated target trial aimed to evaluate whether live HZ vaccination reduces the long-term risk of hepatobiliary diseases in older adults. Methods: We conducted a nationwide, population-based cohort study in South Korea (n = 2,207,784 individuals aged ≥ 50 years) from January 1, 2012, to December 31, 2021, with follow-up until January 31, 2024. This cohort was built by merging health insurance (Korea Health Insurance Review and Assessment Service), national health screening (Korean National Health Insurance Service), and vaccination records (Korea Disease Control and Prevention Agency). To assess the risk of any hepatobiliary diseases and eight subcategories following HZ vaccination, we performed 1:1 exposure-driven propensity score matching and estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models. Results: After matching, 1,462,070 individuals were included (mean age, 61.57 years; 56.26% females). HZ vaccination was associated with a 14% lower risk of developing any hepatobiliary events (aHR 0.86, 95% CI 0.85–0.87). Risk reductions were consistent across all subcategories, notably for hepatic failure (aHR 0.71, 95% CI 0.63–0.78) and liver cirrhosis (aHR 0.74, 95% CI 0.70–0.77). Protective associations were more pronounced in males, younger individuals (< 60 years), and smokers. The benefit persisted for eight years, peaking within the first four years. Conclusions: HZ vaccination was associated with significantly reducing hepatobiliary and pancreatic diseases, supporting potential broader health benefits beyond shingles prevention in older adults.