Hepatitis A vaccination and its public-health impact in routine prevention and outbreak control: a systematic review and meta-analysis

Abstract

Background Hepatitis A vaccination is used for routine prevention and outbreak control, but its effectiveness and population-level impact have not been comprehensively synthesised. We aimed to assess vaccine effectiveness, certainty of evidence, and population-level impact. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, Biological Abstracts, and CENTRAL for studies published from 1st January 1985 to 1st April 2026. Randomised controlled trials and observational studies with an unvaccinated comparison group were eligible if they assessed pre-exposure or post-exposure hepatitis A vaccination and reported effect estimates or sufficient data for their calculation. Estimates were pooled using a DerSimonian–Laird random-effects model. Risk of bias was assessed with RoB 2 and ROBINS-I, and certainty of evidence with GRADE. Ecological studies evaluating vaccine impact before and after implementation of paediatric vaccination programmes were analysed separately. The review was registered with PROSPERO (CRD420261308908). Findings We included 21 publications in the meta-analysis and 19 studies in the population-level impact analysis. Pooled effectiveness of pre-exposure vaccination was 95·8% (95% CI 93·1–97·4; I 2 = 29·9%), supported by moderate-certainty evidence. In paediatric populations, effectiveness was 97·5% (92·8–99·1; I 2 = 20·1%) in randomised trials and 95·9% (93·0–97·6; I 2 = 0·0%) in cohort studies. Effectiveness was 97·2% (93·8–98·8; I 2 = 4·3%) for inactivated vaccines and 96·0% (93·2–97·6; I 2 = 0·0%) for live attenuated vaccines. Pooled effectiveness of post-exposure vaccination was 96·9% (89·3–99·1; I 2 = 89·7%), but certainty of evidence was very low. Ecological studies showed consistently high population-level impact, generally ranging from 80% to 100%. Interpretation Hepatitis A vaccination provides very high protection in pre-exposure settings. Post-exposure vaccination may also be effective, but confidence in this estimate is limited by very low-certainty evidence and substantial heterogeneity. Population-level findings support the public health value of routine immunisation and suggest potential benefit in outbreak response. Funding Cooperatio 31 fund, Health Sciences, Charles University, Prague, Czech Republic.