High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial
Open Access
- 23 April 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 52 (2), 472-479
- https://doi.org/10.1002/hep.23727
Abstract
In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial using UDCA (13‐15 mg/kg/day) was unable to confirm these results. Accordingly, a randomized, placebo‐controlled study was initiated with a high dose of UDCA (23‐28 mg/kg/day). The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score (NAS). With the modified Brunt score, 185 patients with histologically proven NASH were randomized [intention to treat (ITT)], and 147 were treated per protocol (PP). With the NAS, 137 patients were confirmed to have NASH, 48 had borderline NASH, and 1 did not have NASH. The treatment time was 18 months. At entry, the treatment groups were comparable. A second biopsy sample was obtained from 139 of 185 patients (NAS: 107/137). The primary criterion for evaluation was a change in the liver histology; the secondary criteria were single histological variables and liver biochemistry. Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score (P = 0.881) or NAS (P = 0.355). Only lobular inflammation improved significantly (P for the modified Brunt score = 0.011, P for NAS = 0.005). In subgroup analyses, significant improvements in lobular inflammation were also observed in males, younger patients up to 50 years of age, slightly overweight patients, and patients with hypertension and an increased histology score. The fibrosis score did not change (P for ITT = 0.133, P for PP = 0.140). With the exception of γ‐glutamyl transferase, UDCA did not improve laboratory data. Conclusion: High‐dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo. Hepatology 2010This publication has 33 references indexed in Scilit:
- Design and validation of a histological scoring system for nonalcoholic fatty liver diseaseHepatology, 2005
- The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsiesJournal of Hepatology, 2005
- Plasma adiponectin is decreased in nonalcoholic fatty liver diseaseActa Endocrinologica, 2005
- 4-Hydroxynonenal as a selective pro-fibrogenic stimulus for activated human hepatic stellate cellsJournal of Hepatology, 2004
- Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndromeHepatology, 2003
- Expanding the natural history of nonalcoholic steatohepatitis: From cryptogenic cirrhosis to hepatocellular carcinomaGastroenterology, 2002
- Gene expression of tumor necrosis factor [alpha ] and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patientsHepatology, 2001
- Nonalcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnormalitiesGastroenterology, 2001
- Nonalcoholic Steatohepatitis: A Proposal for Grading and Staging The Histological LesionsThe American Journal of Gastroenterology, 1999
- Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severityGastroenterology, 1999