Increased Soluble Fas and Fas Ligand Levels in Patients with Nonalcoholic Steatohepatitis

Abstract

Purpose: To test the association of death receptor proteins soluble FAS (sFAS) and soluble FAS Ligand (sFASL) with nonalcoholic steatohepatitis (NASH) independent of known confounders and their correlation with disease severity and insulin resistance. Methods: Plasma sFAS and sFASL were measured using a sandwich ELISA based immunoassay in 70 patients undergoing liver biopsy with clinical suspicion of NAFLD. Histology was assessed in a blinded manner and the NAFLD activity score was calculated for each sample. In parallel sFAS and FASL levels were measured in patients with Hepatitis C (validation set) and the levels in hepatitis C patients were compared with sFAS and sFASL levels in NASH patients. Results: Of the 70 study subjects,37 patients had NASH, 20 had steatosis and 13 normal liver biopsy. Mean age was 49 (±11) years, 45.7% were male and 84% Caucasians. The mean body mass index (BMI) was 31.7 (±4.9) kg/m2 and the median triglycerides and HOMA index were 158 (94–210) mg/dL and 3 (1–7.4) respectively. Patients with NASH had significantly higher levels of both sFAS and sFASL than patients with steatosis and normal liver biopsy (Table 1). NASH patients had significantly higher level of sFASL than Hepatitis C patients (Table 1). sFAS and sFASL showed strong positive correlation with degree of fibrosis (r = 0.499 and 0.315, P < .001 and P= .008 respectively). Positive correlation was also seen between sFAS and HOMA (r = 0.336, P= .007). On multivariate analyses, a 10 pg/ml increase in sFASL increased the odds of having NASH by 60% 1.6 (1.04–2.5, P= 0.034); a 1 ng/ml increase in sFAS levels increased the odds by 40% 1.4 (1.2–1.6, P= 0.003) and a 10 IU/L increase in liver enzymes showed only a 20% increase in the odds of having NASH 1.2 (1.00–1.4, P= 0.093) (Table 2).Table 2: Prognostic value of sFAS and sFASL in prediction of NASHTable 1: sFAS and sFASL levels are highest in patients with NASHConclusion: The data implicates a significant role for sFAS/sFASL interaction in NAFLD progression. This concept merits further investigation as a potential diagnostic and therapeutic strategy.