Value of hepatitis B virus core-related antigen in predicting the natural course of chronic hepatitis B and liver fibrosis regression

Objective To investigate the clinical value of hepatitis B virus core-related antigen ( HBcrAg) in predicting the natural course of chronic hepatitis B ( CHB) and liver fibrosis regression. Methods A total of 138 CHB patients who were admitted to 302 Hospital of PLA, The First Affiliated Hospital of Zhengzhou University, and Fuzhou Infectious Disease Hospital from January 2013 to December 2015 were enrolled and divided into HBeAg-positive group with 69 patients and HBeAg-negative group with 69 patients. Of all patients, 109 with an Ishak score of ≥3 were treated with entecavir for 72 weeks. Liver biopsy specimens and serum were collected at baseline and after 72 weeks of treatment to observe histopathology and HBcrAg level. The t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two group. The chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was also performed. The area under the receiver operating characteristic curve ( AUC) was used to analyze the value of HBcrAg in the diagnosis of liver fibrosis. Results In HBeAg-positive CHB patients, serum HBcrAg level was negatively correlated with liver fibrosis stage ( r =-0. 342, P = 0. 004) ; in HBeAg-negative CHB patients, serum HBcrAg level was positively correlated with liver fibrosis stage and inflammation ( r = 0. 439 and 0. 437, both P < 0. 001) . In HBeAg-positive patients, serum HBcrAg level had an AUC of 0. 705 in predicting advanced liver fibrosis and 0. 701 in predicting liver cirrhosis ( both P < 0. 05) ; in HBeAg-negative CHB patients, serum HBcrAg level had AUCs of0. 815, 0. 815, 0. 726, and 0. 675 in predicting mild liver fibrosis, marked liver fibrosis, advanced liver fibrosis, and liver cirrhosis, respectively ( all P < 0. 05) . After antiviral therapy, the group with a high serum HBcrAg level was more likely to experience liver fibrosis regression than that with a low level ( 53. 7% vs 32. 7%, χ2= 4. 888, P = 0. 027) . The patients with liver fibrosis regression had a significantly greater reduction in serum HBcrAg level than those without regression[1. 5 ( 0. 4-3. 2) log IU/ml vs 0. 8 ( 0. 1-1. 8) log IU/ml, Z =-1. 724, P = 0. 042]. Conclusion Serum HBcrAg can be used as a new marker in predicting liver fibrosis stage and liver fibrosis regression in clinical practice.