Nine women with symptomatic precirrhotic
primary biliary cirrhosis have been treated with oral pulse
methotrexate, 15 mg/wk, for 12-34 months. Three women had
pruritus, two
fatigue, and four
pruritus and
fatigue.
Itching disappeared and
fatigue lessened or disappeared in all within 4-11 months after starting
methotrexate. All who itched were able to discontinue
cholestyramine (five) or
antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when
methotrexate was discontinued or the dose lowered. Mean serum
alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum
bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum
alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum
cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum
cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum
cholesterol levels were elevated.
Serum albumin remained normal in all. The serum
bilirubin levels became normal in three of four patients with elevated levels. The serum
alkaline phosphatase levels became normal in four patients and the
alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal
inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that
methotrexate may be effective treatment for precirrhotic
primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.