Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone.

Methotrexate (2.5 mg/day) was used in addition to ursodeoxycholic acid (10-15 mg/kg per day) in 8 female patients with primary biliary cirrhosis. All patients had undergone ursodeoxycholic acid treatment for more than 6 months preceding this study and their serum alkaline phosphatase remained constant at more than 300 U/l for more than 2 months. One patient showed histologic stage I, three stage II, two stage III and two stage IV disease. Within 6 months, fatigue and itching disappeared in all symptomatic patients. Serum alkaline phosphatase activities improved dramatically (621 +/- 299 to 378 +/- 258, mean +/- S.D.) in all but one patient and normalized in four. Serum gamma-glutamyltransferase activities (180 +/- 99 U/l vs. 150 +/- 125 U/l) and immunoglobulin M concentrations (616 +/- 424 vs. 362 +/- 195 mg/dl) also improved. Adverse effects of methotrexate therapy were only regularly observed within the first 2-6 weeks, such as fatigue and transient enhancement of transaminases and serum bile acid concentrations. We conclude that methotrexate may be a highly effective drug for the treatment of primary biliary cirrhosis in patients whose symptoms and/or laboratory liver function tests are not improved enough by ursodeoxycholic acid alone. However, its influence on histology and the natural history of the disease needs to be established.