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Methotrexate-associated hepatotoxicity: retrospective analysis of 210 patients with rheumatoid arthritis
W J Shergy1, R P Polisson, D S Caldwell
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Purpose:
Beginning in the 1980s, methotrexate has been used successfully to treat rheumatoid arthritis. The magnitude and severity of short- and long-term methotrexate toxicity, however, have not been adequately investigated. Our study was performed to determine the prevalence of hepatotoxicity in patients with rheumatoid arthritis receiving long-term methotrexate therapy.
Patients And Methods:
We conducted a retrospective, computer-assisted review of all Duke University Medical Center patients undergoing liver biopsy for methotrexate monitoring from January 1979 to January 1988. A total of 538 biopsies were performed in 399 patients, 259 of whom had inflammatory arthritis (210 with rheumatoid arthritis, 47 with psoriatic arthritis, and two with seronegative spondyloarthropathy).
Results:
No evidence of cirrhosis was defined in the cohort with rheumatoid arthritis; however, six patients with rheumatoid arthritis had histologic changes of fibrotic liver disease (prevalence of 2.9 percent in the group with rheumatoid arthritis) while taking methotrexate. Five of the six patients were obese and three had glucose intolerance or overt diabetes mellitus, and one person admitted to alcohol usage. Only one patient with fibrotic liver disease had elevated liver function test results, and no person showed a declining serum albumin level at the time of biopsy. Sixty-one patients with rheumatoid arthritis underwent multiple samplings (44 with two, 13 with three, and four with four biopsies). Fourteen of these patients showed progressive hepatic disease, whereas four patients improved.
Conclusion:
Although the prevalence of methotrexate hepatotoxicity in this large cohort of patients with rheumatoid arthritis was low, a small but definite risk of hepatic fibrosis, not predictable by laboratory screening, still exists.
Insights
Methotrexate for rheumatoid arthritis can cause liver fibrosis in 2.9% of patients. This risk exists even with normal lab tests, highlighting the need for careful monitoring during long-term methotrexate therapy.
Area of Science:
- Rheumatology
- Hepatology
- Pharmacology
Background:
- Methotrexate (MTX) has been a cornerstone in rheumatoid arthritis (RA) treatment since the 1980s.
- The long-term toxicity profile of MTX, particularly hepatotoxicity, requires further investigation.
- Understanding MTX-induced liver injury is crucial for patient safety in chronic RA management.
Purpose of the Study:
- To determine the prevalence of hepatotoxicity in rheumatoid arthritis patients undergoing long-term methotrexate therapy.
- To assess the risk of liver fibrosis associated with methotrexate use in RA.
- To evaluate the effectiveness of current laboratory screening in predicting MTX-related liver damage.
Main Methods:
- Retrospective review of Duke University Medical Center patient data from 1979-1988.
- Analysis of 538 liver biopsies from 399 patients, including 210 with rheumatoid arthritis.
- Inclusion criteria focused on patients undergoing liver biopsy for methotrexate monitoring.
Main Results:
- A 2.9% prevalence of fibrotic liver disease was observed in rheumatoid arthritis patients on methotrexate.
- Six out of 210 RA patients exhibited liver fibrosis; five were obese, and three had diabetes or glucose intolerance.
- Only one patient with fibrosis had elevated liver function tests, and none showed declining albumin levels.
Conclusions:
- Methotrexate hepatotoxicity, specifically liver fibrosis, occurs at a low but significant rate in RA patients.
- Hepatic fibrosis risk associated with methotrexate may not be reliably predicted by standard laboratory screening.
- Continuous monitoring and awareness of potential methotrexate-induced liver injury are essential for rheumatoid arthritis management.