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.
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.
Authors: Kris V Kowdley; Patricia Belt; Laura A Wilson; Matthew M Yeh; Brent A Neuschwander-Tetri; Naga Chalasani; Arun J Sanyal; James E Nelson Journal: Hepatology Date: 2011-12-06 Impact factor: 17.425
Authors: Heather M Patton; Katherine Yates; Aynur Unalp-Arida; Cynthia A Behling; Terry T-K Huang; Philip Rosenthal; Arun J Sanyal; Jeffrey B Schwimmer; Joel E Lavine Journal: Am J Gastroenterol Date: 2010-04-06 Impact factor: 10.864
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: Ariel E Feldstein; Anna Wieckowska; A Rocio Lopez; Yao-Chang Liu; Nizar N Zein; Arthur J McCullough Journal: Hepatology Date: 2009-10 Impact factor: 17.425
Authors: Ruyue Shao; Yongqiang Yang; Kerui Fan; Xicheng Wu; Rong Jiang; Li Tang; Longjiang Li; Yi Shen; Gang Liu; Li Zhang Journal: Int J Med Sci Date: 2021-10-25 Impact factor: 3.738