Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy

Ursodeoxycholic acid is widely used as the standard therapy for the treatment of primary biliary cirrhosis and other cholestatic liver diseases. Although it has been shown to improve biochemical markers and delay disease progression, its effect upon fatigue and pruritus, is at best uncertain. To assess the safety and efficacy of methotrexate for treating symptomatic primary biliary cirrhosis patients who were biochemical partial responders or non-responders to ursodeoxycholic acid therapy. We treated eight consecutive primary biliary cirrhosis patients with methotrexate who were followed in a single hepatology clinical practice, who were symptomatic, and who had had an incomplete biochemical response to ursodeoxycholic acid therapy. Pruritus and fatigue were assessed at each clinic visit and graded from 0 (asymptomatic) to 4 (incapacitating). The median dose of methotrexate was 13.75 mg/week (range 7.5-15) and the mean duration of methotrexate therapy was 49 months (range 11-126). At the end of follow-up pruritus in six of seven patients had improved, and fatigue in all patients had improved with the addition of methotrexate therapy (pruritus: baseline 2.9 +/- 1.1 vs. end of treatment 0.6 +/- 1.5, P <= 0.0175, and fatigue: baseline 3.0 +/- 0.8, vs. end of treatment 1.0 +/- 0.8, P <= 0.0023). Improvement in symptoms was associated with a significant improvement in biochemical markers of cholestasis. No significant adverse effects of methotrexate were documented. Methotrexate should be considered as a potential additive treatment for symptomatic primary biliary cirrhosis patients who are incomplete biochemical responders to ursodeoxycholic acid therapy.