Matthew J Gurka1, Jasmine A Mack1, Xiaofei Chi1, Mark D DeBoer2. 1. Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. 2. Department of Pediatrics, Division of Pediatric Endocrinology, University of Virginia, Charlottesville, Virginia, USA.
Abstract
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH), which can lead to liver failure, requires liver biopsies to follow and is difficult to treat. Our goal was to assess metabolic syndrome (MetS) severity as a predictor of treatment success and a marker of response. METHODS: We assessed data from the Pioglitazone, Vitamin E, or Placebo for NASH Study, in which individuals with biopsy-confirmed NASH were randomized to receive pioglitazone, vitamin E, or placebo for 96 weeks. We assessed associations of a sex-specific and race/ethnicity-specific MetS severity Z-score (MetS-Z) at baseline and 48 weeks with biopsy-determined endpoint of NASH resolution at 96 weeks. RESULTS: Baseline MetS-Z was inversely associated with odds of NASH resolution (odds ratio [OR] per 1 SD of MetS-Z: 0.47, 95% confidence interval [CI] 0.28, 0.79). Decrease in MetS-Z during initial 48-week intervention was greatest for pioglitazone treatment (effect size: -0.31, 95% CI -0.15, -0.48) and for vitamin E tended toward being greater for those with versus without NASH resolution (-0.18 vs -0.05). Overall, 48-week change in MetS-Z was associated with NASH resolution (OR per 1-SD change: 0.53, 95% CI 0.33, 0.85), although this was attenuated in models that included transaminases, which remained linked to treatment success (OR by change-in-aspartate aminotransferase Z-score: 0.38, 95% CI 0.19, 0.76). CONCLUSIONS: Individuals with more severe metabolic derangement at baseline were less likely to exhibit NASH resolution, suggesting that individuals may have a threshold of MetS severity beyond which successful treatment is unlikely. As an integrated marker of metabolic abnormalities, MetS-Z was correlated with successful treatment, although transaminases were a more consistent marker of NASH resolution.
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH), which can lead to liver failure, requires liver biopsies to follow and is difficult to treat. Our goal was to assess metabolic syndrome (MetS) severity as a predictor of treatment success and a marker of response. METHODS: We assessed data from the Pioglitazone, Vitamin E, or Placebo for NASH Study, in which individuals with biopsy-confirmed NASH were randomized to receive pioglitazone, vitamin E, or placebo for 96 weeks. We assessed associations of a sex-specific and race/ethnicity-specific MetS severity Z-score (MetS-Z) at baseline and 48 weeks with biopsy-determined endpoint of NASH resolution at 96 weeks. RESULTS: Baseline MetS-Z was inversely associated with odds of NASH resolution (odds ratio [OR] per 1 SD of MetS-Z: 0.47, 95% confidence interval [CI] 0.28, 0.79). Decrease in MetS-Z during initial 48-week intervention was greatest for pioglitazone treatment (effect size: -0.31, 95% CI -0.15, -0.48) and for vitamin E tended toward being greater for those with versus without NASH resolution (-0.18 vs -0.05). Overall, 48-week change in MetS-Z was associated with NASH resolution (OR per 1-SD change: 0.53, 95% CI 0.33, 0.85), although this was attenuated in models that included transaminases, which remained linked to treatment success (OR by change-in-aspartate aminotransferase Z-score: 0.38, 95% CI 0.19, 0.76). CONCLUSIONS: Individuals with more severe metabolic derangement at baseline were less likely to exhibit NASH resolution, suggesting that individuals may have a threshold of MetS severity beyond which successful treatment is unlikely. As an integrated marker of metabolic abnormalities, MetS-Z was correlated with successful treatment, although transaminases were a more consistent marker of NASH resolution.
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: Leon A Adams; Oliver R Waters; Matthew W Knuiman; Robert R Elliott; John K Olynyk Journal: Am J Gastroenterol Date: 2009-03-17 Impact factor: 10.864