Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective
therapy is lacking. We therefore evaluated the safety and efficacy of low-dose
cyclosporine in 29 patients with
primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or
portal hypertension. The patients were randomly assigned to receive either
cyclosporine (4 mg per kilogram of
body weight per day) or placebo. After one year 17 of the 19 patients assigned to
cyclosporine had improvement or stability in their degree of
fatigue, and 18 in their degree of
pruritus. In contrast, among the 10 patients assigned to placebo,
fatigue increased in 4 (P less than 0.06) and
pruritus worsened in 6 (P less than 0.001). Those assigned to
cyclosporine also had significant decreases in serum levels of
bilirubin,
alanine aminotransferase,
alkaline phosphatase,
gamma globulin, and the titer of antimitochondrial
antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the
cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued
cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic
primary biliary cirrhosis, immunosuppressive therapy with
cyclosporine is promising and deserves further evaluation.