The purpose of this pilot study was to determine whether daily administration of
cyclosporin A to symptomatic patients with
primary biliary cirrhosis for 1 yr would lead to a significant and sustained improvement in liver
enzyme abnormalities. Twelve adult patients (11 female, 1 male; aged 52.6 +/- 8.9 yr, mean +/- SD) with serologic and histologically defined
primary biliary cirrhosis were randomized to receive either oral
cyclosporin A or vehicle placebo.
Cyclosporin A was administered at sufficient dosages to maintain serum radioimmunoassay trough levels between 100 and 200 ng/ml (starting dosage, 2.5 mg/kg.day). After 1 yr of
therapy, significant changes from pretreatment values were seen only in recipients of
cyclosporin A. These included a 37% decrease in mean serum
alkaline phosphatase and a 43% decrease in
gamma-glutamyltransferase (controls +3% and -14%, respectively). Mean serum
bilirubin and
albumin levels and prothrombin times remained unaltered in the two groups, as did the extent of
inflammation and
fibrosis and the histologic staging of liver biopsy specimens. Although mean serum
creatinine levels increased by 51% in recipients of
cyclosporin A (+2% in controls), there were no associated changes in diastolic blood pressure or
creatinine clearance values. Other side effects including
thrombocytopenia,
hirsutism,
headaches,
tremor, and parasthesiae were common in the treated group but not of sufficient severity to warrant adjustment in the dosage or discontinuation of
therapy. The observed changes in hepatic, renal, and hematologic tests tended to return to baseline after discontinuation of
therapy. Two patients, both placebo recipients, died of
liver failure during the study period. The results of this study indicate that in symptomatic
primary biliary cirrhosis,
cyclosporin A administration is associated with a significant improvement in cholestatic liver
enzyme abnormalities that persists for the
duration of therapy. A progressive rise in serum
creatinine levels and a high incidence of side effects raise concerns regarding the long-term safety of this agent in
primary biliary cirrhosis.