Reactivation of occult hepatitis B virus infection following cytotoxic lymphoma therapy in an anti-HBc negative patient

J Med Virol. 2013 Apr;85(4):597-601. doi: 10.1002/jmv.23513. Epub 2013 Jan 28.


Screening hepatitis B virus (HBV) surface antigen (HBsAg) and HBV core antibody (anti-HBc) is recommended prior to cytotoxic or immunosuppressive therapy. This case describes an anti-HBc negative, DNA positive occult HBV infection in a 71-year-old Caucasian male following rituximab-based treatment for follicular lymphoma. Pre-screening serology indicated negative HBsAg and anti-HBc. However, following sequential treatment cycles the patient developed weak HBsAg with a low HBV DNA load (<1,000 IU/ml), but remained anti-HBc negative. The DNA load peaked 5 months later (>1 × 10(6) IU/ml) and he was subsequently treated with Tenofovir. Currently the patient remains anti-HBc negative, and is anti-HBe negative, anti-HBs negative, HBeAg positive. No clinical or biochemical evidence of hepatitis has occurred. Sequencing and phylogenetic analysis identified the HBV genosubtype as D4, most probably acquired some years ago during a stay in Papua New Guinea, in spite of prior hepatitis B vaccination. Four amino acid substitutions were detected within the HBsAg loop yet none in the core protein. This case questions the dependability of anti-HBc testing and highlights the role of HBV DNA testing prior to and throughout cytotoxic or immunosuppressive regimes. As this case exemplifies, vaccination protects against clinical infection but may not exclude seronegative occult infection with the possibility of reactivation.

Publication types

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

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antiviral Agents / administration & dosage
  • DNA, Viral / blood
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Genotype
  • Hepatitis B / chemically induced*
  • Hepatitis B / drug therapy
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / isolation & purification
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects*
  • Lymphoma / drug therapy*
  • Male
  • Organophosphonates / administration & dosage
  • Papua New Guinea
  • Phylogeny
  • Rituximab
  • Sequence Analysis, DNA
  • Tenofovir
  • Viral Load
  • Virus Activation / drug effects*


  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Immunologic Factors
  • Organophosphonates
  • Rituximab
  • Tenofovir
  • Adenine