In patients with
chronic hepatitis C,
alanine aminotransferase (ALT) levels do not accurately reflect the extent of liver
inflammation. The discrepancy between ALT level and liver damage could be related to the mode of cell death. In the present study, we quantified serum levels of apoptotic
cytokeratin 18 (CK-18) neoepitopes that are generated by activated
caspases during apoptosis. Apoptotic CK-18 neoepitopes were quantified by
enzyme linked
immunosorbent assay in sera from patients with
chronic hepatitis C and elevated ALT levels (n = 72), patients with
chronic hepatitis C and persistently normal ALT levels (n = 27) and healthy controls (n = 19). Serum CK-18 neoepitope levels were strongly correlated with ALT (r = 0.659, P < 0.0001) and the histology activity index (r = 0.374, P < 0.001). Patients with
chronic hepatitis C and persistently normal ALT levels had higher apoptotic CK-18 neoepitope levels than healthy controls (P = 0.03) but lower levels than patients with
chronic hepatitis C and elevated ALT levels (P < 0.001). Highest serum CK-18 neoepitope levels were observed in patients with
cirrhosis (P = 0.002). Hence apoptotic CK-18 neoepitopes in serum of patients with
chronic hepatitis C are associated with ALT level and histological liver damage. Serum apoptotic CK-18 neoepitope levels are elevated both in patients with
chronic hepatitis C and elevated ALT levels as well as in patients with normal ALT levels indicating that also patients with
chronic hepatitis C and normal ALT have an increased hepatocyte loss by apoptosis.