title: Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial.
abstract: The primary aim of this study was to compare the effects of pentoxifylline (PTX) versus placebo on the histological features of nonalcoholic steatohepatitis (NASH). In all, 55 adults with biopsy-confirmed NASH were randomized to receive PTX at a dose of 400 mg three times a day (n = 26) or placebo (n = 29) over 1 year. The primary efficacy endpoint was defined as improvement in histological features of NASH through reduction in steatosis, lobular inflammation, and/or hepatocellular ballooning as reflected by a decrease of ≥ 2 points in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 1 year, intention-to-treat analysis showed a decrease of ≥ 2 points in the NAS in 38.5% of patients on PTX versus 13.8% of those on placebo (P = 0.036). Per protocol analysis, a decrease of ≥ 2 points in the NAS from baseline was observed in 50% of the patients on PTX versus 15.4% of those on placebo (P = 0.01). The mean change in NAS score from baseline was -1.6 in the PTX group, versus -0.1 in the placebo group (P < 0.001). PTX significantly improved steatosis (mean change in score -0.9 versus -0.04 with placebo, P < 0.001) and lobular inflammation (median change -1 versus 0 with placebo, P = 0.02). No significant effects in hepatocellular ballooning were observed. PTX also improved liver fibrosis (mean change in fibrosis score was -0.2 among those on PTX versus +0.4 among those on placebo, P = 0.038). Although not statistically significant (P = 0.17), improvement in fibrosis was observed in a greater proportion (35%) of patients in the PTX group compared to placebo (15%). Adverse effects were similar in both groups.
  
  
  CONCLUSIONS
  PTX improved histological features of NASH compared to placebo. PTX was well tolerated in patients with NASH.
authors: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44915, USA. zeinc@ccf.org
authors: Claudia O
authors: CO
authors: Zein
authors: Lisa M
authors: LM
authors: Yerian
authors: Prema
authors: P
authors: Gogate
authors: Rocio
authors: R
authors: Lopez
authors: John P
authors: JP
authors: Kirwan
authors: Ariel E
authors: AE
authors: Feldstein
authors: Arthur J
authors: AJ
authors: McCullough
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001706:Biopsy; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010431:Pentoxifylline