Combining the HBcrAg decline and HBV mutations predicts spontaneous HBeAg seroconversion in chronic hepatitis B patients during the immune clearance phase

Objective

To assess predictive ability of hepatitis B virus (HBV) markers and genome mutations for spontaneous hepatitis B e antigen (HBeAg) seroconversion.

Methods

A total of 113 chronic hepatitis B (CHB) patients were followed up for 76 weeks without antiviral treatment. Baseline basal core promoter (BCP) and precore mutations were detected and serum hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen (HBcrAg) and HBV DNA levels were serially quantified.

Results

Eighteen patients experienced spontaneous HBeAg seroconversion (Group A), and the left 95 patients did not experience spontaneous HBeAg seroconversion (Group B). At week 28, HBsAg (P=0.03) and HBcrAg (P=0.01) levels were significantly different between Group A and B. Reduced HBsAg (P=0.02) and HBcrAg (P<0.01) levels from baseline to week 28 were significantly different between two groups. Multivariate logistic regression showed that lower HBcrAg (OR=1.02, P=0.03) levels at week 28, and HBcrAg levels with sharp decrease at week 28 (OR=0.19, P=0.02) were related with spontaneous HBeAg seroconversion. The areas under the receiver operating characteristic curve (AUROC) showed that reduction in HBcrAg levels from baseline to week 28 (0.93, P=0.001, 95% CI: 0.74–1.08) have excellent prediction value. The mutation frequencies of A1574T (51.11% vs 18.18%, P=0.001), G1862A (30.00% vs 13.03%, P=0.001), G1896A (27.22% vs 5.45%, P=0.001) and C1913G (32.78% vs 12.73%, P=0.001) in Group A were significantly higher than Group B.

Conclusions

Baseline A1574T, G1862A, G1896A and C1913G mutations and HBcrAg levels with sharp decrease at week 28 were associated with spontaneous HBeAg seroconversion.

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