Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: Results of a randomized trial

Abstract

No effective medical therapy is available for all patients with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) has been suggested to be of benefit based on open label clinical studies. We randomized 166 patients with liver biopsy-proven NASH to receive between 13 and 15 mg/kg/d of UDCA or placebo for 2 years. End points included changes in liver test results and liver histology at 2 years of therapy. The treatment groups were comparable at entry with regard to age, gender, risk factors for NASH, serum liver biochemistries, and baseline liver histology. A total of 126 patients completed 2 years of therapy. Pre-and posttreatment liver biopsies were available in 107 patients for review at the end of the study. UDCA was well tolerated and body weight was stable during the study duration. Serum liver biochemistries were stable or improved in both the UDCA and placebo-treated groups. Changes in the degree of steatosis, necroinflammation, or fibrosis that occurred with therapy were not significantly different between the UDCA and placebo groups. In conclusion, 2 years of therapy with UDCA at a dose of 13 to 15 mg/kg/d, although safe and well tolerated, is not better than placebo for patients with NASH. (HEPATOLOGY 2004; 39:770 -778.)

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…Until further data supporting its effectiveness become available, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis (Strength -1, Quality -C) Ursodeoxycholic acid (UDCA), Omega-3 fatty acids, and Miscellaneous Agents Several studies 126,[137][138][139][140] investigated UDCA (conventional and high doses) to improve aminotransferases and steatosis in patients with NAFLD and liver histology in patients with NASH. All but one study 139 have been proof-of-concept studies with small numbers of participants and/or surrogate endpoints. Notably, a single large multicenter RCT convincingly showed that UDCA offers no histological benefit over placebo in patients with NASH.…”

“…Notably, a single large multicenter RCT convincingly showed that UDCA offers no histological benefit over placebo in patients with NASH. 139 Omega-3 fatty acids, currently approved in the United States to treat hypertriglyceridemia, have been investigated to treat NAFLD both in animal models and in humans. 141 A recent review by Masterton et al, 142 of published literature related to omega-3 fatty acids in NAFLD, found experimental evidence to support their use but the interpretation of human studies was limited by small sample size and methodological flaws.…”

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

“…Seven RCTs (639 participants, 21% diabetic; three RCTs with post-treatment histology, five RCTs with a low risk of bias) evaluated UDCA in NAFLD (ESM Table 5) [82][83][84][85][86][87][88].…”

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

“…Numerous other antioxidants show efficacy in treating fatty liver diseases and include Nacetylcysteine [166], zinc [167,168], silymarin [169], and ursodeoxycholic acid [170], just to name a few. Please refer to the following excellent review articles for additional information on antioxidant therapy for treatment of fatty liver diseases from multiple causes [144,[171][172][173][174].…”