Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy--pathogenesis and management

Rev Med Virol. Sep-Oct 2001;11(5):287-99. doi: 10.1002/rmv.322.


In an endemic area for chronic hepatitis B infection, reactivation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. Careful prospective serological testing has shown that hepatitis B virus reactivation is a two-staged process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterised by enhanced viral replication, as reflected by increases in the serum levels of hepatitis B virus DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase and infection of naïve hepatocytes with hepatitis B virus. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure and even death. The occurrence and severity of hepatitis B virus reactivation after various cytotoxic or immunosuppressive therapy is unpredictable and treatment has been disappointing, largely due to the late administration of therapy. Recently, pre-emptive treatment of chronic hepatitis B patients undergoing cytotoxic or immunosuppressive therapy, with potent nucleoside analogues has shown some promising results. Further controlled studies are needed to define the incidence and risk factors of hepatitis B reactivation so that pre-emptive treatment with nucleoside analogues could be administered to those patients at high risk of disease.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antiviral Agents / therapeutic use*
  • DNA Polymerase III / blood
  • DNA, Viral / blood
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / growth & development*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Recurrence
  • Virus Activation / drug effects*


  • Antineoplastic Agents
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Immunosuppressive Agents
  • DNA polymerase A
  • DNA Polymerase III