- 1Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, United States.
- 2Department of Pediatrics, Division of Pediatric Endocrinology, PO Box 800386, University of Virginia, Charlottesville, Virginia, United States.
Background and aim: Non-alcoholic steatohepatits (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 NASH Study (PIVENS), 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- 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-score: 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, CI -0.15,-0.48) and for vitamin-E tended toward being greater for those with vs. without NASH resolution (-0.18 vs. -0.05). Overall, 48-week change in MetS-Z was associated with NASH resolution (OR of per 1-SD change: 0.53, CI 0.33,0.85), though this was attenuated in models that included transaminases, which remained linked to treatment success (OR by change-in-AST Z-score: 0.38, 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, though transaminases were a more consistent marker of NASH resolution.