Randomized Controlled Trial Testing the Effects of Weight... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Randomized Controlled Trial Testing the Effects of Weight Loss on Nonalcoholic Steatohepatitis

Promrat, Kittichai1,4,*; Kleiner, David E.3; Niemeier, Heather M.2,5; Jackvony, Elizabeth2; Kearns, Marie2; Wands, Jack R.1; Fava, Joseph L.2; Wing, Rena R.2

1_Division of Gastroenterology and Hepatology, The Warren Alpert Medical School of Brown University, Providence, RI_

2_Weight Control and Diabetes Research Center, The Warren Alpert Medical School of Brown University, Providence, RI_

3_Laboratory of Pathology, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD_

4_Providence Veterans Affairs Medical Center, Providence, RI_

5_Department of Psychology, University of Wisconsin-Whitewater, WI_

*Address reprint requests to: Division of Gastroenterology and Hepatology, The Warren Alpert Medical School of Brown University, 110 Lockwood Street, Suite 116, Providence, RI 02903. Email:[email protected]; fax: 401-444-6316.

Received 1 July 2009; Accepted 19 August 2009

Published online 9 September 2009 in Wiley InterScience (www.interscience.wiley.com).

Supported by the National Institutes of Health, 5R03DK67263-2. Supported in part by the Intramural Research Program of the National Cancer Institute, NIH (D.E.K).

Potential conflict of interest: Nothing to report.

Abstract

Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that is strongly associated with obesity. Currently, there is no approved therapy for NASH. Weight reduction is typically recommended, but efficacy data are lacking. We performed a randomized controlled trial to examine the effects of lifestyle intervention using a combination of diet, exercise, and behavior modification, with a goal of 7% to 10% weight reduction, on clinical parameters of NASH. The primary outcome measure was the change in NASH histological activity score (NAS) after 48 weeks of intervention. Thirty-one overweight or obese individuals (body mass index [BMI], 25–40 kg/m2) with biopsy-proven NASH were randomized in a 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control). After 48 weeks of intervention, participants assigned to LS lost an average of 9.3% of their weight versus 0.2% in the control group ( P = 0.003). A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group (72% versus 30%, P = 0.03). NAS improved significantly in the LS group (from 4.4 to 2.0) in comparison with the control group (from 4.9 to 3.5) ( P = 0.05). Percent weight reduction correlated significantly with improvement in NAS ( r = 0.497, P = 0.007). Participants who achieved the study weight loss goal (≥7%), compared with those who lost less than 7%, had significant improvements in steatosis (−1.36 versus −0.41, P < 0.001), lobular inflammation (−0.82 versus −0.24, P = 0.03), ballooning injury (−1.27 versus −0.53, P = 0.03) and NAS (−3.45 versus −1.18, P < 0.001). Conclusion: Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH. (Hepatology 2009.)