Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2015; 21(2): 541-548
Published online Jan 14, 2015. 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, Akihiro Matsumoto, Takeji Umemura, Soichiro Shibata, Yuki Ichikawa, Takefumi Kimura, Michiharu Komatsu, Eiji Tanaka
Nozomi Kamijo, Akihiro Matsumoto, Takeji Umemura, Soichiro Shibata, Yuki Ichikawa, Takefumi Kimura, Michiharu Komatsu, Eiji Tanaka, Department of Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Author contributions: Kamijo N, Matsumoto A, Umemura T and Tanaka E designed the research; Kamijo N and Matsumoto A performed the research; all the authors contributed to acquisition of data; Kamijo N, Matsumoto A, Umemura T and Tanaka E contributed to analysis and interpretation of data; Matsumoto A performed the statistical analysis; Umemura T and Tanaka E wrote the manuscript; Tanaka E supervised the study.
Supported by Research grant from the Ministry of Health, Labor, and Welfare of Japan.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Takeji Umemura, MD, PhD, Associate Professor, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. tumemura@shinshu-u.ac.jp
Telephone: +81-263-372634 Fax: +81-263-329412
Received: May 7, 2014
Peer-review started: May 8, 2014
First decision: May 29, 2014
Revised: June 17, 2014
Accepted: July 22, 2014
Article in press: July 22, 2014
Published online: January 14, 2015
Processing time: 255 Days and 20.6 Hours
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: Seroconversion; Hepatitis B core-related antigen; Pre-core; Basal core promoter; Mutation; Hepatitis B surface antigen; Hepatitis B virus DNA

Core tip: The exact roles of pre-core (pre-C) and basal core promoter (BCP) mutations remain unclear before and after hepatitis B e antigen (HBeAg) seroconversion. Here, although the pre-C mutant became predominant in the HBeAg seroconversion group during follow-up, the proportion of the BCP mutation did not change. Hepatitis B virus (HBV) viral markers were significantly higher in patients without the mutations in an HBeAg positive status. HBV DNA and hepatitis B surface antigen levels were higher in patients with the pre-C mutation in an anti-HBe positive status. Taken together, the association of the pre-C mutation on viral load appears to be opposite before and after HBeAg seroconversion in patients with HBV infection.