Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis.

OBJECTIVE To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX). METHODS We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case-control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease. RESULTS Twenty-four cases of cirrhosis and liver failure were identified, giving a 5-year cumulative incidence of approximately 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease. CONCLUSION Serious liver disease is an uncommon, age- and dose-related complication of low-dose MTX therapy for RA.

[1]  K. Tolman,et al.  Hepatic ultrastructure after methotrexate therapy for rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[2]  R. Sturrock,et al.  Clinical associations between arthritis and liver disease. , 1982, Annals of the rheumatic diseases.

[3]  R. Auerbach,et al.  Methotrexate hepatotoxicity in psoriasis. Consideration of liver biopsies at regular intervals. , 1980, Archives of dermatology.

[4]  K. Tolman,et al.  Methotrexate and the liver. , 1985, The Journal of rheumatology. Supplement.

[5]  J. Kremer,et al.  Electron microscopic analysis of sequential liver biopsy samples from patients with rheumatoid arthritis. Correlation with light microscopic findings. , 1989, Arthritis and rheumatism.

[6]  H. Maibach,et al.  Methotrexate guidelines--revised. , 1982, Journal of the American Academy of Dermatology.

[7]  R. Smallwood,et al.  Low‐dose methotrexate therapy and hepatotoxicity The view of the hepatologist , 1991, The Medical journal of Australia.

[8]  M. Weinblatt,et al.  The liver in rheumatic diseases. , 1982, Seminars in arthritis and rheumatism.

[9]  G. Alarcón,et al.  Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-term treatment. , 1989, Arthritis and rheumatism.

[10]  L. Moreland,et al.  Prospective analysis of liver biopsies before and after methotrexate therapy in rheumatoid patients. , 1989, Seminars in arthritis and rheumatism.

[11]  J. Kremer,et al.  Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. , 1989, Arthritis and rheumatism.

[12]  M. Weinblatt,et al.  Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis. 84-month update. , 1992, Arthritis and rheumatism.

[13]  D. Pisetsky,et al.  Methotrexate-associated hepatotoxicity: retrospective analysis of 210 patients with rheumatoid arthritis. , 1988, The American journal of medicine.

[14]  H. Frenzel,et al.  Liver biopsy findings in patients with rheumatoid arthritis undergoing longterm treatment with methotrexate. , 1989, The Journal of rheumatology.

[15]  D. Furst,et al.  Acute, reversible hepatic failure associated with methotrexate treatment of rheumatoid arthritis. , 1989, The Journal of rheumatology.

[16]  A. Nyfors.  Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.