Fatal hepatic failure associated with hepatitis B virus reactivation in a hepatitis B surface antigen-negative patient with rheumatoid arthritis receiving low dose methotrexate

Clin Exp Rheumatol. Nov-Dec 2007;25(6):888-9.


A 66-year-old female patient with rheumatoid arthritis, who had been HBsAg-negative and anti-HBs-positive, developed hepatic dysfunction following low-dose methotrexate therapy. Serologic testing for HBsAg, HBeAg, IgM HBc and HBV DNA were positive. Despite antiviral therapy with lamivudine, the hepatic condition gradually deteriorated until the patient died. Since HBV replication persists in the liver even in individuals with resolved HBV infection (i.e., HBsAg-negative, anti-HBs-positive), HBV reactivation may occur in these patients with immunosuppression. Therefore, especially in endemic areas, all patients being considered for immunosuppressive therapy should be closely monitored with liver function tests and evaluated for HBV reappearance even when HBsAg-negative.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / drug therapy*
  • Fatal Outcome
  • Female
  • Hepatitis B Antibodies / analysis
  • Hepatitis B Antigens / analysis*
  • Hepatitis B Surface Antigens / immunology
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Lamivudine / therapeutic use
  • Liver Failure / etiology*
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Virus Activation


  • Hepatitis B Antibodies
  • Hepatitis B Antigens
  • Hepatitis B Surface Antigens
  • Immunosuppressive Agents
  • Lamivudine
  • Methotrexate