Establishment of a Seronegative Occult Infection With an Active Hepatitis B Virus Reservoir Enriched of Vaccine Escape Mutations in a Vaccinated Infant After Liver Transplantation

J Infect Dis. 2019 Nov 6;220(12):1935-1939. doi: 10.1093/infdis/jiz411.

Abstract

We describe the establishment of a seronegative occult hepatitis B virus (HBV) infection (OBI) in a successfully vaccinated infant who underwent liver transplantation from an donor positive for antibody to hepatitis B core antigen (anti-HBc). The use of highly sensitive droplet digital polymerase chain reaction assays revealed a not negligible and transcriptionally active intrahepatic HBV reservoir (circular covalently closed DNA, relaxed circular DNA, and pregenomic RNA: 5.6, 2.4, and 1.1 copies/1000 cells, respectively), capable to sustain ongoing viral production and initial liver damage. Next-generation sequencing revealed a peculiar enrichment of hepatitis B surface antigen vaccine-escape mutations that could have played a crucial role in OBI transmission. This clinical case highlights the pathobiological complexity and the diagnostic challenges underlying OBI.

Keywords: HBV reservoir; digital droplet PCR; hepatitis B occult infection; liver transplantation; vaccine escape mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Child, Preschool
  • DNA, Viral
  • Female
  • Hepatitis B / diagnosis*
  • Hepatitis B / etiology
  • Hepatitis B / prevention & control
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Humans
  • Liver / immunology
  • Liver / pathology
  • Liver / virology
  • Liver Transplantation* / adverse effects
  • Mutation*
  • Polymerase Chain Reaction
  • Vaccination
  • Virus Replication

Substances

  • Biomarkers
  • DNA, Viral