The histologic effects of low-dose methotrexate therapy for primary biliary cirrhosis

Objective. - Primary biliary cirrhosis is a progressive liver disease that is believed to be autoimmune in nature. Treatment, at best, may slow the progression of the disease, although no therapy has been able to halt its progression. Preliminary data suggest a beneficial effect of methotrexate in the treatment of primary biliary cirrhosis. We evaluated the histologic effect of 2 years of treatment with methotrexate. Design. - Liver biopsies were obtained before methotrexate was started and after 2 years of therapy. Ninety-six paired biopsies from 48 patients with primary biliary cirrhosis were reviewed by a pathologist who was blinded to all clinical history and sequence of the biopsies. Variables 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, steatosis, 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 was a trend toward progression of the stage of the disease, portal fibrosis, bile duct loss, fat, and pleomorphism over the 2 years and toward regression in piecemeal necrosis, bile duct injury, ductular proliferation, granulomas, and lobular inflammation and necrosis. Conclusion. - After 2 years of treatment with methotrexate, the stage of disease and fibrosis of primary biliary cirrhosis continue to progress, although overall, inflammation and bile duct injury decrease with methotrexate treatment.