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

Abstract

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.