Treatment of primary sclerosing cholangitis with oral methotrexate.

Ten patients with well-documented primary sclerosing cholangitis who had no signs of portal hypertension or liver failure were treated with oral pulse methotrexate for at least 1 yr. The methotrexate dose averaged 15 mg/wk (0.2 mg/kg/wk). All six patients who were symptomatic became asymptomatic within 1-5 months of starting methotrexate. Biochemical tests of liver function improved in all patients. The alkaline phosphatase value decreased from a mean (+/-SD) of 373 +/- 210 IU to 140 +/- 77 IU (p = 0.0008), the mean alanine aminotransferase (ALT) from 115 +/- 74 to 76 +/- 79 U/L (p = 0.005), and the mean aspartate aminotransferase (AST) value from 88 +/- 37 to 57 +/- 40 U/L (p = 0.007). The improvement in mean bilirubin (1.19 +/- 1.41 to 0.67 +/- 0.25 mg/dl) was not statistically significant. Serum albumin remained normal (3.97 +/- 0.46 to 4.22 +/- 0.36 g/dl). Nine patients had a repeat liver biopsy after 1 yr of methotrexate therapy. Six of the nine showed histologic improvement with a reduction in inflammation. The other three liver biopsies were unchanged. Repeat cholangiograms were done in six patients. Two showed improvement. In one of the two, who had early disease, the cholangiogram became normal, and the liver biopsy was markedly improved. The other four cholangiograms showed no progression of disease. No toxicity was detected in these 10 patients. These results suggest that low-dose oral methotrexate therapy is effective in primary sclerosing cholangitis if treatment is begun before signs of portal hypertension or liver failure occur.