THE HISTOLOGIC EFFECTS OF LOW-DOSE METHOTREXATE THERAPY FOR PRIMARY BILIARY-CIRRHOSIS

Objective.-Primary biliary cirrhosis is a progressive liver disease th at is believed to be autoimmune in nature. Treatment, at best, may slo w the progression of the disease, although no therapy has been able to hart its progression. Preliminary data suggest a beneficial effect of methotrexate in the treatment of primary biliary cirrhosis. We evalua ted the histologic effect of 2 years of treatment with methotrexate. D esign.-Liver biopsies were obtained before methotrexate was started an d after 2 years of therapy. Ninety-six paired biopsies from 48 patient s with primary biliary cirrhosis were reviewed by a pathologist who wa s blinded to all clinical history and sequence of the biopsies. Variab les examined included stage of the disease, degree of portal fibrosis, portal inflammation and piecemeal necrosis, bile duct injury or loss, bile ductular proliferation, lobular inflammation and necrosis, steat osis, granulomas, cholestasis, and nuclear pleomorphism of hepatocytes . Results.-In most categories, pretreatment and posttreatment biopsies did not reflect a change over the 2-year period of treatment. There w as a trend toward progression of the stage of the disease, portal fibr osis, bile duct loss, fat, and pleomorphism over the 2 years and towar d regression in piecemeal necrosis, bile duct injury, ductular prolife ration, granulomas, and lobular inflammation and necrosis. Conclusion. -After 2 years of treatment with methotrexate, the stage of disease an d fibrosis of primary biliary cirrhosis continue to progress, although overall, inflammation and bile duct injury decrease with methotrexate treatment.