LAUSR

Hepatic lipid peroxidation is a key pathogenic event in the progression from NAFLD to the more severe inflammatory and fibrotic lesions of non-alcoholic steatohepatitis (NASH). This more advanced stage of the disease is a major risk factor for cirrhosis and hepatocellular carcinoma. Steatosis and inflammation of the liver are associated with an impaired metabolism and function of α-tocopherol, the main fat-soluble antioxidant of the cellular membranes and circulating lipoproteins. With this background, an increased vitamin E oxidation rate should occur in NAFLD. The lack of unbiased pre-analytical and analytical protocols leaves this assumption unsupported. A new LC-MS/MS analytical procedure was thus set up to measure the vitamin E oxidation metabolite α-TQ in human plasma. The application of this procedure in a pilot observation study demonstrated increase α-TQ levels in NAFLD patients in association with increased 4-hydroxynonenal (4-HNE) protein adducts and decreased polyunsaturated fatty acid (PUFA) levels. In conclusion these findings point to a role of α-TQ as a causal biomarker of lipid peroxidation and impaired liver metabolism of vitamin E in NAFLD.