The relation between serum cytokeratin 18 fragment level and liver histopathology in inactive hepatitis B virus carriers and active chronic hepatitis B patients

Background and aims: Hepatic apoptosis has a major role in pathogenesis of chronic liver disease. Cytokeratin 18 (CK18) is a well known substrate of caspases existed during hepatic apoptosis. In our study we aimed to evaluate the relation between serum CK18 fragment level and the grade of hepatic injury in inactive hepatitis B virus (HBV) carriers and active chronic hepatitis B (CHB) patients.Methods: Inactive HBV carriers (n=104), active CHB patients (n=100) and healthy controls (n=43) were enrolled to the study and serum CK18 fragment levels were measured. All the patients except healthy controls were evaluated histopathologically with liver biopsy.Results: In inactive HBV carriers moderate to severe histological activity index (HAI) (?4/18) ratio was 24% (25/104) and fibrosis (?2/6) rate was 33% (34/104). In active CHB patients moderate to severe HAI (?4/18) ratio was 72% (72/100) and fibrosis (?2/6) rate was 65% (65/100). Serum CK18 fragment levels were significantly higher in inactive HBV carriers (198.77±77.62 U/L) than healthy controls (142.92±40.18 U/L) (p=0.001) and also higher in active CHB patients (283.02±147.45 U/L) than inactive HBV carriers (p=0.001). The diagnostic accuracy of CK18 to differentiate HBeAg negative CHB patients from inactive HBV carriers was found moderate (c-statistic: 0.695) and the cut-off level for CK18 in diagnosis was found 262 U/L (specificity: 85%; sensitivity: 48%; positive likelihood ratio: 3.35 and negative likelihood ratio: 0.60). Also in ALT normal HBeAg negative CHB patients the diagnostic accuracy of CK18 was found moderate (c-statistic: 0.677). Both in inactive HBV carriers and active CHB patients there was a positive correlation between the serum CK18 fragment levels and HAI and ALT levels. But there was no correlation with HBV-DNA levels and fibrosis staging.Conclusions: Serum CK18 fragment levels are related with liver injury grade in CHB patients and may be used as a predictive factor for necroinflammation. For differential diagnosis of inactive HBV carriers and HBeAg negative CHB patients CK18 may be a useful test used with ALT and HBV-DNA levels. Also, inactive HBV carrier state is not an innocent process and early histopathologic evaluation may be needed.Key Words: Inactive hepatitis B virus carriers, Chronic hepatitis B, Cytokeratin 18, Liver, Histopathology