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

Abstract

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.

Keywords: Apoptosis; Chronic hepatitis B; Cytokeratin-18; Inactive carrier; Significant inflammation.