To investigate the pre-C/BCP mutation and quasispecies in patients with hepatitis B virus e antigen (HBeAg) positive (eP-CHB) and the relationship with the levels of HBeAg and HBV DNA.

The pre-C/BCP mutation was detected in 220 patients with eP-CHB from January 2016 to December 2018 admitted in Beijing You’an Hospital, Capital Medical University by cross-sectional study. Among whom, the pre-C/BCP region in 24 patients was amplified and cloned. Serum HBeAg and HBV DNA levels were detected simultaneously. The pre-C/BCP mutation and quasispecies and the relationship with HBeAg and HBV DNA levels were analyzed, respectively.

Among the 220 patients with eP-CHB, total mutation rate of pre-C/BCP was 70.0% (154/220), co-mutation rate of pre-C/BCP was 18.2% (40/220) and mutation rate of pre-C and BCP were 30.9% (68/220) and 57.3% (126/220), respectively. The detection rates of the above four mutations in patients with HBV DNA ≥ 5 lgIU/ml were all higher than those of patients with HBV DNA < 5 lgIU/ml, the rates of BCP mutation and pre-C/BCP total mutation were significantly different (χ² = 5.809, P = 0.016; χ² = 5.081, P = 0.024). The lower HBeAg level was (< 500 COI, 500-1 000 COI and > 1 000 COI), the higher detection rates of the above four mutations were, all with significant difference (χ² = 31.738, 17.291, 16.263, 22.164; all P < 0.001). Similarly, among the cases with HBV DNA ≥ 5 lgIU/ml, the detection rates of the above four mutations were higher among the cases with lower HBeAg level, with significant differences (χ² = 40.503, 19.654, 16.727, 29.119; all P < 0.001). In quasispecies detection, HBeAg level of cases with high mutation of the pre-C region was lower than that with low mutation, with significant difference (t = 2.230, P = 0.017). There was no significant difference between HBV DNA levels of cases with high mutation and low mutation of the pre-C region (t = 0.624, P = 0.462) and BCP (t = 0.893, P = 0.317).

There were still extensive pre-C/BCP mutations in eP-CHB. The mutation rates of pre-C and BCP were higher in patients with high HBV DNA and low HBeAg level. The high proportion of pre-C mutants in quasispecies had more influence on HBeAg expression. Combined with the previous studies, it was speculated that the pre-C/BCP mutation may be the cause of low HBeAg and high HBV DNA in eP-CHB and lead to the recurrence after withdrawal of antiviral therapy.