Evidence-Based Medicine
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 5039-5048
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.5039
Hepatitis B virus preS1 deletion is related to viral replication increase and disease progression
Seoung-Ae Lee, Ki-Jeong Kim, Hong Kim, Won-Hyuk Choi, Yu-Sub Won, Bum-Joon Kim
Seoung-Ae Lee, Hong Kim, Bum-Joon Kim, You-Sub Won, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea
Ki-Jeong Kim, Department of Microbiology, School of Medicine, Chung-Ang University, Seoul 110-799, South Korea
Won-Hyuk Choi, Department of Internal Medicine, Konkuk University, Seoul 110-799, South Korea
Author contributions: Kim BJ conceived this research and participated in its design and coordination; Lee SA, Kim KJ, Kim H and Choi WH performed the experiments and analyzed and interpreted the data; Choi WH and Won YS contributed the reagents, materials, and analysis tools; all authors approved the final manuscript; Lee SA, Kim KJ and Kim H equally contributed into this study.
Supported by Grants from National Research Foundation of Korea; grant funded by the Korean government (Ministry of Education, Science, and Technology), No. 2013-005810; and Foundation of Seoul National University Hospital (SNUH research fund), No. 0320140140.
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: Bum-Joon Kim, Professor, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. kbumjoon@snu.ac.kr
Telephone: +82-2-7408316 Fax: +82-2-7430881
Received: September 23, 2014
Peer-review started: September 25, 2014
First decision: October 14, 2014
Revised: October 30, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 28, 2015
Abstract

AIM: To investigate the clinical implications of hepatitis B virus (HBV) preS1 deletion.

METHODS: We developed a fluorescence resonance energy transfer-based real-time polymerase chain reaction (RT-PCR) that can detect four genotypes (wild type, 15-bp, 18-bp and 21-bp deletion). The PCR method was used in two cohorts of Korean chronic HBV subjects with genotype C infections. Cohort I  included 292 chronic HBV subjects randomly selected from Cheju National University Hospital (Jeju, South Korea) or Seoul National University Hospital (Seoul, South Korea), and cohort II included 90 consecutive chronic HBV carriers recruited from Konkuk University Hospital (Seoul, South Korea); the cohort II patients did not have hepatocellular carcinoma or liver cirrhosis.

RESULTS: The method proposed in this study identified 341 of 382 samples (89.3%). Deletion variants were identified in 100 (29.3%) of the 341 detected samples. In both cohorts, the subjects with deletions had a significantly higher Hepatitis B virus e antigen (HBeAg)-positive seroprevalence [cohort I, wild (51.0%) vs deletion (75.0%), P < 0.001; cohort II, wild (69.2%) vs deletion (92.9%), P = 0.002] and higher HBV DNA levels [cohort I, wild (797.7 pg/mL) vs deletion (1678.9 pg/mL), P = 0.013; cohort II, wild (8.3 × 108 copies/mL) vs deletion (2.2 × 109 copies/mL), P = 0.049], compared to subjects with wild type HBV.

CONCLUSION: HBV genotype C preS1 deletion may affect disease progression in chronic HBV subjects through an extended duration of HBeAg seropositive status and increased HBV replications.

Keywords: Hepatitis B virus, PreS1 start codon deletion, Hepatitis B virus e antigen, Hepatocellular carcinoma, Genotype C

Core tip: Our data indicate that the hepatitis B virus (HBV) genotype C preS1 deletion might significantly contribute to disease progression in chronic HBV subjects through an extended duration of Hepatitis B virus e antigen seropositive status and increased HBV replication. This study provides novel insight into the greater infectivity and virulence of genotype C compared with other genotypes. In addition, the fluorescence resonance energy transfer-based real-time polymerase chain reaction used to detect the preS1 deletion shows promise for the earlier prediction of the risk of liver disease progression in chronic HBV subjects.