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. 2015 Jan 14;21(2):541-8.
doi: 10.3748/wjg.v21.i2.541.

Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion

Nozomi Kamijo  1 , Akihiro Matsumoto  1 , Takeji Umemura  1 , Soichiro Shibata  1 , Yuki Ichikawa  1 , Takefumi Kimura  1 , Michiharu Komatsu  1 , Eiji Tanaka  1
Affiliations

Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion

Nozomi Kamijo et al. World J Gastroenterol. .

Abstract

Aim: To investigate the role of pre-core and basal core promoter (BCP) mutations before and after hepatitis B e antigen (HBeAg) seroconversion.

Methods: The proportion of pre-core (G1896A) and basal core promoter (A1762T and G1764A) mutant viruses and serum levels of hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), and HB core-related antigen were analyzed in chronic hepatitis B patients before and after HBeAg seroconversion (n = 25), in those who were persistently HBeAg positive (n = 18), and in those who were persistently anti-HBe positive (n = 43). All patients were infected with HBV genotype C and were followed for a median of 9 years.

Results: Although the pre-core mutant became predominant (24% to 65%, P = 0.022) in the HBeAg seroconversion group during follow-up, the proportion of the basal core promoter mutation did not change. Median HBV viral markers were significantly higher in patients without the mutations in an HBeAg positive status (HBV DNA: P = 0.003; HBsAg: P < 0.001; HB core-related antigen: P = 0.001). In contrast, HBV DNA (P = 0.012) and HBsAg (P = 0.041) levels were significantly higher in patients with the pre-core mutation in an anti-HBe positive status.

Conclusion: There is an opposite association of the pre-core mutation with viral load before and after HBeAg seroconversion in patients with HBV infection.

Keywords: Basal core promoter; Hepatitis B core-related antigen; Hepatitis B surface antigen; Hepatitis B virus DNA; Mutation; Pre-core; Seroconversion.

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Figures

Figure 1
Figure 1
Comparison of changes in pre-core (A) and basal core promoter (B) mutation type among 3 groups of patients classified according to hepatitis B e antigen /anti-hepatitis B e positive status. A: A significant difference was seen in patients with hepatitis B e antigen (HBeAg) seroconversion (P = 0.022). One patient whose pre-core (pre-C) mutation was undetermined at the start of follow-up was wild type at the end point; B: Of the 3 patients whose basal core promoter (BCP) mutation was undetermined at the start of follow-up, 2 were wild type and 1 was undetermined at the end point. HBeAg: Hepatitis B e antigen.
Figure 2
Figure 2
Comparison of serum hepatitis B virus DNA, hepatitis B surface antigen, and hepatitis core-related antigen levels among patients with wild (-/-) and mutant types of the pre-core and basal core promoter mutations. Fifty-seven of 61 samples obtained from HBeAg positive cases and 86 of 111 samples obtained from anti-HBeAg positive cases were eligible for analysis. HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; HBcrAg: Hepatitis core-related antigen; pre-C: Pre-core; BCP: Basal core promoter.
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