Development of fulminant hepatitis B (precore variant mutant type) after the discontinuation of low-dose methotrexate therapy in a rheumatoid arthritis patient

Arthritis Rheum. 2001 Feb;44(2):339-42. doi: 10.1002/1529-0131(200102)44:2<339::AID-ANR51>3.0.CO;2-Q.


A 75-year-old female rheumatoid arthritis patient who was positive for hepatitis B surface antigen and for antibodies to hepatitis Be antigen showed liver dysfunction, and therefore methotrexate (MTX) therapy was discontinued. Her drug lymphocyte stimulation test indicated positivity for MTX. Her liver dysfunction improved briefly, but she developed fulminant hepatitis with elevated levels of hepatitis B virus (HBV)/DNA polymerase and subsequently died. HBV/DNA analysis performed with polymerase chain reaction-mutation site-specific assay revealed that the fulminant hepatitis was caused by a precore mutant virus. Sudden reactivation of the immune system by discontinuation of MTX may have led to the attack on infected cells. Even when hepatitis Be antibodies are present, MTX should not be used in patients who have chronic infection with HBV.

Publication types

  • Case Reports

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Variation
  • Hepatitis B / chemically induced*
  • Hepatitis B virus / genetics
  • Humans
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Mutation
  • Time Factors


  • Methotrexate