No studies of adjusted methotrexate were found. Forty-seven studies that looked at liver toxicity in patients who took methotrexate were included. Most were cohort studies and two were case-control studies; no further details were provided on the design of individual studies. No quality assessment results were reported.
Rheumatoid arthritis: The incidence rate of elevated liver enzymes in the first three years was 13/100 patient-years and the cumulative incidence was 31% (95% CI 29% to 33%; 18 studies, 2,199 patients), although this varied according to the cut-off used. In patients with elevated liver enzymes, methotrexate was permanently discontinued in 7% of patients, paused or reduced in 26% and continued without any adjustment in 67%.
After around four years of methotrexate, liver biopsies showed mild fibrosis in 15.3% of cases (95% CI 13.2% to 17.4%), severe fibrosis in 1.3% (95% CI 0.6% to 2%) and cirrhosis in 0.5% (95% CI 0.1% to 0.9%) (34 studies, 1,154 patients); for pre-treatment biopsies the results were 9% mild fibrosis, severe fibrosis 0.3% and cirrhosis 0.3% (372 patients).
Psoriatic arthritis: Liver biopsies showed mild fibrosis in 9.9% of cases, moderate fibrosis in 1.4% and cirrhosis in 1.4%.
Further results were reported.