Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection

Background/Aim: In chronic hepatitis C and non-alcoholic fatty liver disease, apoptotic caspases are activated in liver and serum caspase activity has been suggested as 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 lesions in HBeAg-negative chronic hepatitis B virus (HBV) infection. Patients/Methods: Cytokeratin-18 fragment levels (U/L) were significantly lower in 30 healthy controls (154±31) than in 53 inactive carriers (172±24, P=0.003) than in 62 chronic hepatitis B patients (474±488, P<0.001). Receiver operating characteristic curve showed excellent diagnostic accuracy (c-statistic:0.87) for differentiating inactive carriers from chronic hepatitis B patients. Cytokeratin-18 fragment cut-off level of 240 U/L gave sensitivity of 60% and specificity and positive predictive value of 100% for chronic hepatitis B diagnosis. Cytokeratin-18 fragment levels were also lower in inactive carriers than in 16 chronic hepatitis B patients with transiently normal ALT (327±256, P=0.001) offering good accuracy for such a differentiation (c-statistic:0.78). In chronic hepatitis B patients, serum cytokeratin-18 fragments correlated positively with ALT/AST, viremia, grading score and their immunohistochemical hepatic expression and negatively with platelet counts, but not with fibrosis or steatosis severity. Conclusions: Serum apoptotic caspase activity is strongly associated with presence of liver injury in patients with HBeAg-negative chronic HBV infection. Cytokeratin-18 fragment levels seem to be a very useful marker for differentiation between inactive HBV carrier state and HBeAg-negative chronic hepatitis B, but not for estimation of the severity of liver histological lesions among HBeAg-negative chronic hepatitis B patients.