Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: Results of a prospective double-blind trial

Background & Aims: Ursodeoxycholic acid (UDCA) is used for treatment of pri mary biliary cirrhosis. Previous studies showed that, compared with UDCA mo no-therapy, bile salts plus prednisolone had no further effect on laborator y data but improved liver histology. Thirty percent of these patients had p rednisolone-related side effects. Budesonide is a glucocorticoid with a hig h receptor affinity and a high first-pass metabolism. In this study we inve stigated whether budesonide and UDCA are superior to UDCA mono-therapy. Met hods: A 2-year prospective, controlled double-blind trial was performed. Tw enty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (gr oup A), and 19 patients (1 dropped out for personal reasons) were treated w ith UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum co rtisol levels, and adrenocorticotropin-stimulated cortisol secretion were a ssessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry. Results: Compared with pretreatment values, liver e nzyme and immunoglobulin M and G levels decreased significantly in both gro ups. Improvement in group A was significantly more pronounced (P < 0.05) th an in group B. Titers of antimitochondrial antibodies did not change. In gr oup A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patie nt in group A had budesonide-related side effects; in 3 patients in group B , complications of liver disease developed. Conclusions: Combination therap y with UDCA and budesonide is superior to UDCA and placebo.