Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n ‫؍‬ 77), at stages I to III, were randomized into 2 treatment arms, A (n ‫؍‬ 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n ‫؍‬ 36): UDCA 15mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A ‫؍‬ 37 and B ‫؍‬ 32). Stage improved 22% in group A but deteriorated 20% in group B (P ‫؍‬ .009). Fibrosis decreased 25% in group A but increased 70% in group B (P ‫؍‬ .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P ‫؍‬ .02), but only 10% in group B (P ‫؍‬ NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P ‫؍‬ .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects. (HEPATOLOGY 2005;41:747-752.) P rimary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease of unknown etiology characterized by small bile-duct destruction, which may eventually progress to hepatic fibrosis, biliary cirrhosis, and liver failure. 1 Ursodeoxycholic acid (UDCA) is a safe medical therapy widely used in the treatment of PBC. Although it has been shown to improve biochemical markers in PBC, 2,3 two recent metaanalyses 4,5 and a Cochrane review 6 showed controversial results concerning its effect on liver histology and patient survival. The latest combined analysis of 4 placebo-controlled UDCA studies showed histological benefit in stages I to II, but the rate of progression was not significantly lower in the UDCA group in stages I to III. 7 A recent 12-year prospective randomized study of UDCA was unable to show any demonstrable effect on long-term outcome of PBC. 8 Combination of prednisolone with UDCA has improved liver histology but at the cost of serious glucocorticoid-dependent side effects. 9 For the moment, UDCA has remained the only approved medical therapy for PBC.Budesonide is a nonhalogenated glucocorticoid absorbed in the small intestine. Of an oral dose, 90% is metabolized during the first liver pass in healthy individuals. After hepatic uptake, budesonide is metabolized to two major metabolites: 16␣-hydroxy-prednisolone and 6␤-hydroxy-budesonide. Glucocorticoid activity of these

FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.

Reassuringly, half of the IBD patients on the TNFα-blocking maintenance therapy achieved deep remission. The majority of patients in deep remission also achieved histological remission.

SUMMARY Background/aimTo evaluate the safety of budesonide in primary biliary cirrhosis.