Pentoxifylline improves nonalcoholic steatohepatitis: A... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Pentoxifylline improves nonalcoholic steatohepatitis: A randomized placebo-controlled trial

Zein, Claudia O.1,2,3,*; Yerian, Lisa M.1; Gogate, Prema2; Lopez, Rocio1; Kirwan, John P.1; Feldstein, Ariel E.1; McCullough, Arthur J.1,3

1_Cleveland Clinic, Cleveland, OH_

2_Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH_

3_Case Western Reserve University, Cleveland, OH_

*Address reprint requests to: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44915

Email: [email protected]

Published online 24 August 2011 in Wiley Online Library(wileyonlinelibrary.com).

Potential conflict of interest: Nothing to report.

Presented, in part, at the Annual Meeting of the American College of Gastroenterology (ACG), October 2010, San Antonio, TX.

Supported by the American College of Gastroenterology Junior Faculty Career Development Award to Dr. Claudia Zein. Dr. Claudia Zein is also supported by Grant Number KL2 RR024990 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. This project was supported by Grant Number M01 RR00080 and Grant Number UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

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. Conclusion: PTX improved histological features of NASH compared to placebo. PTX was well tolerated in patients with NASH (ClinicalTrials.gov number NCT00590161). (Hepatology 2011)