Data from Ectodysplasin A is increased in nonalcoholic fatty liver disease, but is not associated with type 2 diabetes.docx

<b>CONTEXT:</b> Ectodysplasin A (EDA) was recently identified as a liver-secreted protein that is increased in the liver and plasma of obese mice and causes skeletal muscle insulin resistance.<b>OBJECTIVE:</b> To determine if liver and plasma EDA is associated with worsening non-alcoholic fatty liver disease (NAFLD) in obese patients and to evaluate plasma EDA as a biomarker for NAFLD.<b>DESIGN AND SETTING:</b> Cross-sectional study in a public hospital.<b>PATIENTS, INTERVENTIONS AND MAIN OUTCOME MEASURES:</b> Patients with a body mass index &gt;30 kg/m²(n=152) underwent liver biopsy for histopathology assessment and fasting liver EDA mRNA. Fasting plasma EDA levels were also assessed. Non-alcoholic fatty liver (NAFL) was defined as &gt;5% hepatic steatosis and nonalcoholic steatohepatitis (NASH) as NAFLD activity score ≥3.<b>RESULTS:</b> Patients were divided into three groups: No NAFLD (n=45); NAFL (n=65); and NASH (n=42). Liver <i>EDA</i> mRNA was increased in patients with NASH compared with No NAFLD (P=0.05), but not NAFL. Plasma EDA levels were increased in NAFL and NASH compared with No NAFLD (P=0.03). Plasma EDA was related to worsening steatosis (P=0.02) and fibrosis (P=0.04), but not inflammation or hepatocellular ballooning. ROC analysis indicates that plasma EDA is not a reliable biomarker for NAFL or NASH. Plasma EDA was not increased in patients with type 2 diabetes and did not correlate with insulin resistance.<b>CONCLUSIONS:</b> Plasma EDA is increased in NAFL and NASH, is related to worsening steatosis and fibrosis but is not a reliable biomarker for NASH. Circulating EDA is not associated with insulin resistance in human obesity.