BACKGROUND & AIMS:Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease for which there is limited therapy available. Insulin sensitizing, anti-inflammatory, and antifibrotic properties of thiazolidinediones support their use in treating NASH. We have evaluated pioglitazone in the treatment of nondiabetic patients with NASH. METHODS: We randomized 74 nondiabetic patients (45 men; median age, 54 y) with histologically proven NASH to 12 months of standard diet, exercise, and eitherplacebo or pioglitazone (30 mg/day). Sixty-one patients (30 placebo, 31 pioglitazone) had liver biopsies both at the beginning and the end of the study. RESULTS: Compared with placebo, pioglitazone therapy was associated with an increase in weight (mean change, -0.55 vs +2.77 kg; P = .04) and a reduction in glucose (+0.4 vs -0.1 mmol/L; P = .02), HbA1c (+0.16% vs -0.18%; P = .006), insulin C peptide level (+42 vs -78 pmol/L; P = .02), alanine aminotransferase level (-10.9 vs -36.2 u/L; P = .009), gamma-glutamyltransferase level (-9.4 vs -41.2 u/L; P = .002), and ferritin (-11.3 vs -90.5 microg/L; P = .01). Histologic features including hepatocellular injury (P = .005), Mallory-Denk bodies (P = .004), and fibrosis (P = .05) were reduced in patients treated with pioglitazone compared with those in the placebo group. CONCLUSIONS:Pioglitazone therapy over a 12-month period in nondiabetic subjects withNASH resulted in improvements in metabolic and histologic parameters, most notably liver injury and fibrosis. Larger extended trials are justified to assess the long-term efficacy of pioglitazone in this patient group.
RCT Entities:
BACKGROUND & AIMS:Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease for which there is limited therapy available. Insulin sensitizing, anti-inflammatory, and antifibrotic properties of thiazolidinediones support their use in treating NASH. We have evaluated pioglitazone in the treatment of nondiabetic patients with NASH. METHODS: We randomized 74 nondiabetic patients (45 men; median age, 54 y) with histologically proven NASH to 12 months of standard diet, exercise, and either placebo or pioglitazone (30 mg/day). Sixty-one patients (30 placebo, 31 pioglitazone) had liver biopsies both at the beginning and the end of the study. RESULTS: Compared with placebo, pioglitazone therapy was associated with an increase in weight (mean change, -0.55 vs +2.77 kg; P = .04) and a reduction in glucose (+0.4 vs -0.1 mmol/L; P = .02), HbA1c (+0.16% vs -0.18%; P = .006), insulin C peptide level (+42 vs -78 pmol/L; P = .02), alanine aminotransferase level (-10.9 vs -36.2 u/L; P = .009), gamma-glutamyltransferase level (-9.4 vs -41.2 u/L; P = .002), and ferritin (-11.3 vs -90.5 microg/L; P = .01). Histologic features including hepatocellular injury (P = .005), Mallory-Denk bodies (P = .004), and fibrosis (P = .05) were reduced in patients treated with pioglitazone compared with those in the placebo group. CONCLUSIONS:Pioglitazone therapy over a 12-month period in nondiabetic subjects with NASH resulted in improvements in metabolic and histologic parameters, most notably liver injury and fibrosis. Larger extended trials are justified to assess the long-term efficacy of pioglitazone in this patient group.
Authors: Ravi Juluri; Raj Vuppalanchi; John Olson; Aynur Unalp; Mark L Van Natta; Oscar W Cummings; James Tonascia; Naga Chalasani Journal: J Clin Gastroenterol Date: 2011-01 Impact factor: 3.062
Authors: Vlad Ratziu; Muhammad Y Sheikh; Arun J Sanyal; Joseph K Lim; Hari Conjeevaram; Naga Chalasani; Manal Abdelmalek; Anezi Bakken; Christophe Renou; Melissa Palmer; Robert A Levine; B Raj Bhandari; Melanie Cornpropst; Wei Liang; Benjamin King; Elsa Mondou; Franck S Rousseau; John McHutchison; Mario Chojkier Journal: Hepatology Date: 2011-12-14 Impact factor: 17.425