Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis

Background There is an urgent need to develop alternatives to liver biopsy in children to diagnose nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease (NAFLD). Increased hepatocyte apoptosis plays a central role in the development of NASH. Aims To evaluate the plasma levels of two markers of apoptosis, soluble Fas (sFas) and soluble Fas ligand (sFasL), in children with NAFLD and assess their utility as biomarkers of disease severity. Methods Children with biopsy-proven NAFLD were included, and blood samples were collected. Patients were divided into NASH and "not NASH.'' We measured plasma sFas and sFasL using specific ELISA immunoassays. Results One hundred and seventeen children with NAFLD were recruited. Average age was 12.2 +/- 2.9 years, 67 % were male, and 58 % had NASH. Patients with NASH had significantly higher levels of sFas and sFasL than patients in the "not NASH'' group (686.0 +/- 186.5 pg/mL versus 594.2 +/- 244.9, p = 0.023 for sFas and 324.9 +/- 146.5 pg/mL versus 221.4 +/- 134.0, p<0.001 for sFasL). sFasL was found to have higher accuracy for predicting the presence of NASH on liver biopsy with an AUC (95 % CI) of 0.714 (0.618, 0.810). A prediction model, the NASH apoptosis score, was generated consisting of plasma sFasL, age, ferritin, transferrin, and triglyceride levels. The area under receiver operating characteristic curve was 0.78 (95 % CI 0.0.69, 0.87). Conclusions Markers of the extrinsic pathway of hepatocyte apoptosis are elevated in children with NASH. sFasL and the NASH apoptosis score are potential novel biomarkers for NASH.