TRIPLE THERAPY WITH URSODEOXYCHOLIC ACID, PREDNISONE AND AZATHIOPRINEIN PRIMARY BILIARY-CIRRHOSIS - A 1-YEAR RANDOMIZED, PLACEBO-CONTROLLED STUDY

Background/Aims: Treatment with ursodeoxycholic acid has been shown to decrease the rate of disease progression in patients with primary bil iary cirrhosis, although the effect is modest. Since primary biliary c irrhosis has many features of an autoimmune disorder, immunosuppressiv es added to ursodeoxycholic acid may be of value in the treatment of p rimary biliary cirrhosis. Methods: A 1-year randomized, double-blind, placebo-controlled trial was carried out in 50 patients with primary b iliary cirrhosis, who had already been treated with ursodeoxycholic ac id for at least 1 year, but had not achieved complete disease remissio n. Patients were randomized to additional prednisone (30 mg per day in itially, tapered to 10 mg daily after 8 weeks) and azathioprine (50 mg daily) or placebo. A subgroup of patients received cyclical etidronat e and calcium. The principal aim of the study was to assess the short- term benefits and risks of the combined bile acid and low-dose immunos uppressive regimen. Primary endpoints were effects on symptoms, liver biochemistry liver histology, bone mass and the occurrence of adverse events. Results: Pruritus (p=0.02), alkaline phosphatase, aspartate am inotransferase, IgM and procollagen-III-propeptide improved significan tly (all p<0.002) in the combined treatment group as compared to the p lacebo group, Histological scores for disease activity and disease sta ge decreased significantly within the combination treatment group (p<0 .001). Conclusions: In patients with primary biliary cirrhosis receivi ng ursodeoxycholic acid, there is an additional beneficial effect of I -year treatment with prednisone and azathioprine on symptoms and bioch emical, fibrogenetic and histological parameters. These results strong ly encourage the evaluation of this triple treatment regimen in long-t erm controlled trials of adequate size to document its effect on clini cal events.