Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis

BACKGROUND: Ursodeoxycholic acid probably is not able to cure primary biliary cirrhosis. Therefore in this study ursodeoxycholic acid was administered together with prednisolone, since monotherapy with glucocorticoids has been shown to have some positive effects. METHODS: Thirty patients with primary biliary cirrhosis (stages I-III) were entered into the study. Fifteen were treated with ursodeoxycholic acid 10 mg.kg-1.day-1 and placebo (group A), 15 with ursodeoxycholic acid and 10 mg prednisolone (group B) for 9 months. Apart from the usual laboratory examinations, liver biopsies were taken from 29 patients before and after therapy. RESULTS: Liver enzymes decreased significantly compared to the initial values in both groups (p < 0.001), but in group B cholestasis-indicating enzymes and the immunoglobulins G and A improved more rapidly. Between both groups the differences for AP, GGT, IgG, IgA and gamma-globulins were significant (p < 0.05), but only for short terms. In group B, liver histology improved significantly (p < 0.003), which correlated with the decrease of IgG. Ursodeoxycholic acid became the predominant bile acid in the serum. Toxic bile acids did not increase. Bone densitometry revealed a slight deterioration of preexisting osteoporosis in one patient. CONCLUSIONS: Although combination therapy with ursodeoxycholic acid and prednisolone was not superior to monotherapy with ursodeoxycholic acid with regard to liver function tests, it had a highly beneficial influence on liver histology. In our previous trials with monotherapy histology remained unchanged. An early decrease in IgG during combination therapy seems to be an indicator of an amelioration of liver histology.