Pilot study of low dose oral methotrexate treatment for primary biliary cirrhosis

Objective: To assess the efficacy of low doses of oral methotrexate as therapy for primary biliary cirrhosis. Methods: Ten symptomatic patients with this disease were treated with methotrexate at a dose of 15 mg/wk in an open label trial. Results: Eight patients completed 1 yr of treatment and six completed 2. Pruritus and fatigue decreased in all patients treated for at least 1 yr. Mean levels of serum alkaline phosphatase, ALT, and IgM were less at 1 and 2 yr than corresponding baseline means. Total serum bilirubin increased in three patients during treatment. Serum aminotransferases and alkaline phosphatase became normal in one patient with stage I disease. Although liver biopsies at 1 and 2 yr revealed a decrease in the intensity of the inflammatory infiltrate, they also showed an increase in fibrosis suggestive of disease progression. Methotrexate was discontinued in five patients: for disease progression in four (one at 4 months, one at 1 yr, and two at 2 Sr) and for intractable pruritus in one (at 4 months). All patients experienced transient mucositis and intermittent dyspepsia. Conclusions: These findings suggest that methotrexate treatment in patients with primary biliary cirrhosis is not beneficial in patients with advanced disease; in patients with early disease, methotrexate may be associated with amelioration of symptoms, reduction in serum biochemical indices of liver disease, and reduction in hepatic inflammation. However, prospective, randomized, controlled trials will be necessary for definitive evaluation of the effects of methotrexate on the quality of life and survival of patients with primary biliary cirrhosis.