Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection

Background: The differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis. Objectives: We investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB. Study design: A total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n= 21), patients with HBeAg-negative hepatitis (n= 95), HBeAg-positive hepatitis (n= 141) and liver cirrhosis (n= 82). Results: Serum M30-antigen levels were correlated significantly not only with AST (r= 0.544, p < 0.001) and ALT (r= 0.315, p < 0.001) and but also inflammatory grading score on liver biopsy (r= 0.240, p < 0.001). Serum M30-antigen level in HBeAg-negative CHB was significantly higher than that of inactive HBV carrier (399.78. U/L vs 148.90. U/L, p < 0.001). Multivariate analysis showed that AST (p < 0.001), albumin (p= 0.009) and M30-antigen (p= 0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344. U/L) and AST (>78. IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value. Conclusions: Serum M30-antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients.