Metabolomic profiling to identify predictors of response to vitamin E for non-alcoholic steatohepatitis (NASH)

PLoS One. 2012;7(9):e44106. doi: 10.1371/journal.pone.0044106. Epub 2012 Sep 19.

Abstract

Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS). The current study utilized samples collected in the PIVENS trial to identify: (1) baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2) end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547) quantified by mass spectrometry was performed in vitamin E responders (n = 16), vitamin E non-responders (n = 15), and placebo responders (n = 15). At baseline, phenyl-propionic acid (Odds ratio: 29.4, p<0.01), indole-propionic acid levels (Odds ratio: 16.2, p<0.01) were directly associated with a subsequent histologic response to vitamin E treatment whereas γ-carboxyethylhydroxychroman (CEHC) levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p<0.02) and gamma-glutamyl valine (Fold change: 0.8, p<0.03) were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine) compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely) to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement) on treatment and support further studies to validate these biomarkers.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Fatty Liver / diagnosis
  • Fatty Liver / drug therapy*
  • Fatty Liver / metabolism*
  • Female
  • Humans
  • Male
  • Metabolome*
  • Metabolomics
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Prognosis
  • Treatment Outcome
  • Vitamin E / therapeutic use*

Substances

  • Biomarkers
  • Vitamin E