Hepatitis A breakthrough infections despite vaccination: A systematic review and meta-analysis

This systematic review and meta-analysis summarized documented breakthrough hepatitis A (HepA) infections and assessed whether they occur more frequently in immunocompromised populations (ICPs).

We searched Medline, Embase, and Global Index Medicus for records on HepA breakthrough infections, defined as symptomatic HepA among previously vaccinated individuals, published 1991-2024 (PROSPERO: CRD42023450205). Risk of bias was assessed with an adapted Newcastle-Ottawa Scale. Moderate and good-quality studies were analyzed using random-effects and Bayesian hierarchical meta-analyses. The primary outcome compared the proportion of ICPs among fully vaccinated (≥50 days before symptoms) confirmed breakthrough cases to that among all virologically confirmed HepA cases. Meta-analyses assessed the proportion of breakthrough infections among confirmed cases.

Of 3345 reports screened, 90 were included, reporting 43,861 HepA cases, including 832 (partially) vaccinated. We identified six confirmed breakthrough infections with proof of complete vaccination (6.4%; 95% confidence interval 2.6-14.3%), including four ICPs (67%). Post-vaccination serology was available in 3/6 cases: two HIV-positive patients were seronegative, and one neutropenic leukemia patient was seropositive but pauci-symptomatic. The pooled proportion of ICPs among confirmed HepA cases was 17.8% (95% confidence interval 7.7-35.9%).

HepA breakthrough infections are rare, but appear more common among ICPs who fail to seroconvert post-vaccination.