A 72-year-old man developed acute hepatitis B infection despite having been fully vaccinated and showing a strong antibody response after vaccination, a case report shows. Genomic sequencing of his virus revealed a D144A mutation in the hepatitis B surface (S) gene — a change previously linked to vaccine escape — underscoring that clinicians should still consider HBV in patients with acute hepatitis even if they report prior vaccination.
The patient initially sought care for heartburn, but physical exam detected an enlarged liver. Laboratory tests showed markedly elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase), high bilirubin, and raised gamma‑glutamyltransferase. Serology was consistent with recent infection: hepatitis B surface antigen (HBsAg) was positive, both IgM and IgG antibodies to hepatitis B core antigen (anti-HBc) were present, and antibodies to hepatitis B e antigen were detected. HBV DNA measured 14,000 IU/mL, supporting a diagnosis of acute hepatitis B rather than chronic infection.
Clinically notable was the patient’s vaccination history: he received three doses of hepatitis B vaccine in 2003 and had an anti-HBs (protective antibody) titer above 1,000 IU/L six weeks after vaccination. At presentation more than two decades later, anti-HBs remained detectable at 345 IU/L, making simple nonresponse to vaccination unlikely. Anti-HBs are the antibodies measured to document vaccine-induced immunity.
Sequencing identified HBV genotype A2 with the D144A substitution in the S gene. That region encodes HBsAg, the target of vaccine-induced antibodies; certain substitutions there can reduce antibody recognition and allow so‑called vaccine-escape infections. The patient denied recent high‑risk exposures such as new sexual partners, blood transfusion, tattoos, or other blood contact.
The patient recovered without antiviral treatment: HBsAg and HBV DNA fell within days and liver tests and HBsAg had normalized by three months. The authors suggested prior vaccination may still have helped prevent progression to chronic HBV despite the symptomatic acute infection.
National surveillance data from the Netherlands (2004–2024) included 2,455 sequenced HBV-positive samples; 87 (3.5%) had HBsAg variants at sites linked in the literature to vaccine escape, with an average annual detection rate of 3.6%. The D144A change was found in only four other strains over that period. The report concludes that vaccine-escape infections appear rare and have not risen substantially in surveillance, but that continued genomic monitoring is important to detect strains with potential public‑health impact. (Leonhard SE et al., Medicine (Baltimore). 2026;105(22):e48735.)
Original Source: https://www.emjreviews.com/microbiology-infectious-diseases/news/vaccinated-patient-develops-acute-hepatitis-b-infection/
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Publish Date: 2026-06-11 12:36:00
