Model for Non-Invasive Diagnosis of NAFLD Incorporating Caspase 3-Cleaved Cytokeratin-18: A Clinical, Serological, and Immunohistochemical Analysis

: It has been suggested that insulin resistance may play a role in pathogenesis of NASH, with hepatocyte apoptosis believed to be the main factor involved in disease progression from simple steatosis to NASH. During apoptosis, cytokeratin-18 (CK-18) is cleaved by caspases and released into serum, a finding that was shown to correlate with the existence of inflammation and fibrosis in patients with NASH. The present study aims to differentiate patients with simple steatosis from those with NASH using CK-18 assessment both in liver tissue and in serum. The present study was conducted on two groups of patients, the first including 44 patients with simple steatosis and the second comprising 106 patients with steatohepatitis. Serum fasting insulin was measured and serum CK-18 was estimated. No significant differences were found between steatohepatitis patients and patients with simple steatosis regarding fasting insulin levels, or HOMA-IR index (P > 0.05 for each). Comparison of serum CK-18 levels between simple and advanced fatty liver patients showed significantly higher concentrations in patients with steatohepatitis than in patients with simple steatosis (P < 0.001). Serum level of CK-18 demonstrated a satisfactory relationship with all pathological variables that allowed differentiation between both entities of nonalcoholic fatty liver disease.