Treatment of primary biliary cirrhosis with low-dose weekly methotrexate.
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.
Gastroenterology Division, New England Medical Center Hospitals, Boston, Massachusetts.
M M
MM
Kaplan
T A
TA
Knox
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001706:Biopsy; D002784:Cholesterol / Q000097:blood; D004341:Drug Evaluation; D005221:Fatigue / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011537:Pruritus / Q000209:etiology; D013921:Thrombocytopenia / Q000139:chemically induced; D000637:Transaminases / Q000097:blood
D002784:Cholesterol; D000637:Transaminases; D000469:Alkaline Phosphatase; D001663:Bilirubin; D008727:Methotrexate