title: Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial.
abstract: 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 15 mg/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.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, 00029 HYKS, Finland. henna.rautiainen@hus.fi
authors.forename: Henna
authors.initials: H
authors.lastname: Rautiainen
authors.forename: Päivi
authors.initials: P
authors.lastname: Kärkkäinen
authors.forename: A-L
authors.initials: AL
authors.lastname: Karvonen
authors.forename: Heimo
authors.initials: H
authors.lastname: Nurmi
authors.forename: Pekka
authors.initials: P
authors.lastname: Pikkarainen
authors.forename: Hannu
authors.initials: H
authors.lastname: Nuutinen
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
mesh_terms: D000328:Adult; D000368:Aged; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011446:Prospective Studies; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005938:Glucocorticoids; D019819:Budesonide; D014580:Ursodeoxycholic Acid