Relation of Apoptosis Marker CK-18 fragment M30 with hepatic Necroinflammation in patients with HBV related Chronic Liver Disease

Abstract

Background and Objective: Caspase-cleaved cytokeratin 18 (CK18 M30) is a potential clinically useful biomarker in liver disease as it is released from hepatocytes during apoptosis. Chronic hepatitis B virus (HBV) infection affects more than 400 million people worldwide. For treatment of chronic hepatitis B, it is very essential to know the necro inflammatory status of liver. Cytokeratin (CK) 18 is an intermediary filament protein, expressed in hepatocytes, which is proteolytically cleaved during liver damage. In this study, we aimed to investigate whether serum CK-18 fragment M30 level significantly related with the hepatic necroinflammatory
activity in patients with HBV related compensated chronic liver disease (CLD)..Methods: This was a prospective observational study. All patients who met the inclusion and exclusion criteria were assessed for liver biopsy. The total sample was 40 patients. This study was conducted in Department of Hepatology, Bangabandhu Sheikh Mujib Medical University. Per cutaneous transthoracic liver biopsy was done. Specimens were sent to department of pathology, BSMMU for METAVIR scoring. Result: Among 40 CHB patients, the highest frequency was found at 21-30 age groups, male 31(77.5%) and female 9(22.5%), the mean HBV DNA PCR was found 5.3±1.7 (IU/ml). The mean AST and ALT were found 40.2±20.2 (U/L) and 66.4±68.2 (U/L) respectively. 16 patients were HBeAg positive and 24 patients were HBeAg negative. CK-18 M30 level in both HBeAg negative CHB patients and HBeAg positive patients were almost similar(128.8±32.91 and 123.9±28.1), Activity METAVIR score of hepatic necro inflammation
reveals, A0 was 0 (0.0%), A1 was 7(17.5%), A2 was 21(52.5%), A3 was 12(30.0%),Correlation between factors and activity METAVIR score on spearman correlation test reveals, Correlation co-efficient (r value)-age was 0.204, GGT was 0.287 , ALT was 0.333, AST was 0.360, Serum CK 18 fragment M30 level was negatively correlated with activity score of hepatic necro inflammation (r= -0.073; p=0.357). The correlation between ALT and AST with activity score were statistically significant (p<0.05). The area under the receiver-operator characteristic (ROC) curves for prediction of serum CK-18 fragment M30 level reveals - area under curve(AUC)
0.307, which gave a cut off value of 100 U/L with 78.8% sensitivity and 14.3% specificity for prediction of significant necro inflammation (A2 and A3). Conclusion: This study indicates there was no correlation between serum CK-18 fragment M30 level and hepatic necroinflammatory activity in patients with HBV related compensated chronic liver disease (CLD). As a result, CK 18 M30 cannot be used as an accurate non-invasive predictor of significant inflammatory activities in patients with CHB.