Cheng J A , Yates K, Aouizerat B, Sanyal AJ, Metabolomic Profiling to Identify Predictors of Response to Vitamin E for Non-Alcoholic Steatohepatitis (Nash). PLoS ONE 2012. 7(9): e44106.
Metabolon results led to:
- Identification of candidate biomarkers that predict NASH patient response to vitamin E therapy
- Identification of biomarkers that track with vitamin E efficacy
- Elucidation of novel insight into the mechanism of action of vitamin E in NASH
Key metabolomic observations:
- 6 metabolites predicted response of NASH patients to vitamin E therapy. These included 2 intestinal metabolites (indolepropionate, 3-pheylpropionate), 2-palmitoylglycerophospho-ethanolamine, myrisoleate, gamma-CEHC and asparagine
- 3 metabolites separated NASH vitamin E responders from non-responders following therapy (gamma-glutamylleucine, gamma-glutamylvaline and sphingosine)
- Decreased sphingosine levels in vitamin E responders may reflect decreased TNF-alpha activity
Nonalcoholic steatosis (NASH) is a common liver disease. Oxidative stress has been implicated, motivating trials with the antioxidant vitamin E where 43% of subjects met the primary endpoint compared to 19% receiving placebo. Given that only some patients with NASH responded to the vitamin E treatment, there is a need to develop methods to identify individuals responsive to the therapy prior to treatment. Further, once treatment is started, surrogate markers of response are needed. Metabolomics was used to assess plasma samples at baseline and following 6 months of vitamin E treatment in 3 groups: placebo responders, vitamin E non-responders, and vitamin E responders. Candidate biomarkers were identified that separated responders from non-responders at baseline and additional markers were discovered that tracked with efficacy of responders. In addition, several novel findings provided insight into the mechanism of action of vitamin E in NASH responders.