Use of metabolic syndrome severity to assess treatment with vitamin E and pioglitazone for non-alcoholic steatohepatitis.

Abstract

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. 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 96weeks. We assessed associations of a sex-specific and race/ethnicity-specific MetS severity Z-score (MetS-Z) at baseline and 48weeks with biopsy-determined endpoint of NASH resolution at 96weeks. 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). 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.