ACUTE hepatitis B infection can rarely occur after vaccination when HBV surface mutations evade antibody recognition.
A 72-year-old fully vaccinated man developed acute hepatitis B virus infection despite a documented high postvaccination antibody response, according to a case report that underscores the need to consider HBV even in vaccinated patients presenting with acute hepatitis.
The patient initially presented with heartburn symptoms, but clinical examination revealed hepatomegaly. Subsequent laboratory testing showed abnormal liver function, including markedly elevated aspartate aminotransferase and alanine aminotransferase levels, elevated bilirubin, and increased gamma-glutamyltransferase. Serologic testing identified hepatitis B surface antigen, immunoglobulin G and immunoglobulin M antibodies against hepatitis B core antigen, and antibodies against hepatitis B e antigen. HBV DNA was also detected at 14,000 IU/mL, supporting a diagnosis of acute hepatitis B infection.
Acute Hepatitis B Infection Despite Documented Immunity
The case was clinically notable because the patient had received three doses of hepatitis B vaccine in 2003 and had an anti-HBs titer of more than 1,000 IU/L 6 weeks after vaccination. At presentation, anti-HBs antibodies remained detectable at 345 IU/L, making simple nonresponse to vaccination unlikely.
Genomic sequencing identified HBV genotype A2 and a D144A mutation in the S gene. This mutation lies within the hepatitis B surface antigen region targeted by vaccine-induced antibodies and has previously been associated with vaccine escape. The patient denied recent risk behavior, including new sexual contacts, blood transfusions, tattoos, or other blood exposure.
Surveillance Supports Ongoing Monitoring
The patient recovered spontaneously without treatment. Within days, HBsAg and HBV DNA decreased, and by 3 months, liver tests and HBsAg had normalized. The authors noted that vaccination may still have helped prevent chronic infection, despite the acute symptomatic presentation.
Dutch surveillance data from 2004 to 2024 identified 2,455 sequenced HBV-positive samples, including 87 cases with HBsAg variants at sites associated with vaccine escape in the literature. These variants represented 3.5% of sequenced cases, with an average annual detection rate of 3.6%. The D144A mutation was found in only 4 other strains during this period.
The findings reinforce that acute hepatitis B infection should not be ruled out solely because a patient is vaccinated. Although vaccine escape appears rare and has not increased substantially in surveillance data, continued genomic monitoring remains important to identify strains with possible public health implications.
Reference
Leonhard SE et al. Acute hepatitis B infection escaping vaccination: A case report. Medicine (Baltimore). 2026;105(22):e48735.
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