Serum apoptotic caspase activity as a marker of severity in chronic hepatitis C virus infection

Background & Aim: Apoptotic caspases are substantially activated in liver of patients with chronic hepatitis C and preliminary data suggest that serum caspase activity may represent a sensitive marker of early liver injury. We investigated whether the serum levels of caspase-generated fragments of cytokeratin-18 are associated with the severity of liver histological lesions in chronic hepatitis C virus (HCV) infection. Methods: We included 134 patients with chronic HCV infection who consecutively underwent liver biopsy as well as 30 healthy controls. Histological liver lesions were evaluated according to the Ishak’s classification. Chronic hepatitis C was considered to be present in cases with grading score ≥4 and/or stage ≥2, while cases with grading score <4 and stage <2 were classified into chronic HCV infection with minimal histological lesions. The levels of caspase-generated cytokeratin-18 fragments were blindly measured in stored serum samples. Results: Cytokeratin-18 fragments levels (U/L) were significantly lower in the 30 healthy subjects (154±31) than in the 28 HCV-positive patients with minimal histological lesions (196±71, P=0.006) than in the 106 patients with histological chronic hepatitis C (295±202, P<0.001). ROC curve analysis showed that serum levels of CK-18 fragments offered moderate diagnostic accuracy for differentiating chronic hepatitis C patients from chronic HCV patients with minimal histological lesions [c-statistic: 0.67 (95% CI: 0.56-0.77)]. Conclusions: Serum apoptotic caspase activity is associated with the severity of liver histological lesions in chronic HCV infection, but it has moderate diagnostic accuracy in differentiating chronic HCV patients with and without histological lesions of chronic hepatitis.