Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis

Authors

  • Kittichai Promrat,

    Corresponding author
    1. Division of Gastroenterology and Hepatology, The Warren Alpert Medical School of Brown University, Providence, RI
    2. Providence Veterans Affairs Medical Center, Providence, RI
    • Division of Gastroenterology and Hepatology, The Warren Alpert Medical School of Brown University, 110 Lockwood Street, Suite 116, Providence, RI 02903
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    • fax: 401-444-6316.

  • David E. Kleiner,

    1. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD
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  • Heather M. Niemeier,

    1. Weight Control and Diabetes Research Center, The Warren Alpert Medical School of Brown University, Providence, RI
    2. Department of Psychology, University of Wisconsin-Whitewater, WI
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  • Elizabeth Jackvony,

    1. Weight Control and Diabetes Research Center, The Warren Alpert Medical School of Brown University, Providence, RI
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  • Marie Kearns,

    1. Weight Control and Diabetes Research Center, The Warren Alpert Medical School of Brown University, Providence, RI
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  • Jack R. Wands,

    1. Division of Gastroenterology and Hepatology, The Warren Alpert Medical School of Brown University, Providence, RI
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  • Joseph L. Fava,

    1. Weight Control and Diabetes Research Center, The Warren Alpert Medical School of Brown University, Providence, RI
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  • Rena R. Wing

    1. Weight Control and Diabetes Research Center, The Warren Alpert Medical School of Brown University, Providence, RI
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  • 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.)

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