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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Genomic change in hepatitis B virus associated with development of hepatocellular carcinoma
Danbi Lee, Heather Lyu, Young-Hwa Chung, Jeong A Kim, Priya Mathews, Elizabeth Jaffee, Lei Zheng, Eunsil Yu, Young Joo Lee, Soo Hyung Ryu
Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
Heather Lyu, Priya Mathews, Elizabeth Jaffee, Lei Zheng, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21218, United States
Eunsil Yu, Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
Young Joo Lee, Department of Hepatobiliary Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
Soo Hyung Ryu, Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul 04551, South Korea
Author contributions: Lee D and Lyu H contributed equally to this work; Chung YH is a corresponding author; Lee D, Lyu H, Chung YH designed the study, provided collection and analyses of the data and wrote the manuscript; Kim JA, Mathews P and Ryu SH conducted the experimental work; Chung YH, Jaffee E and Zheng Lwere involved in editing the manuscript; Yu E and Lee YJ provided the collection of human material.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Asan Medical Center.
Informed consent statement: Waiver of Informed Consent for this study has been granted by the Institutional Review Board of Asan Medical Center due to demonstrated minimal risk.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: All the anonymous dataset is available on request from the corresponding author at yhchung@amc.seoul.kr
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: Young-Hwa Chung, MD, PhD, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea.
yhchung@amc.seoul.kr
Telephone: +82-2-30103184 Fax: +82-2-4760824
Received: February 2, 2016
Peer-review started: February 2, 2016
First decision: March 7, 2016
Revised: March 21, 2016
Accepted: April 7, 2016
Article in press: April 7, 2016
Published online: June 21, 2016
Processing time: 132 Days and 2.2 Hours
AIM: To determine the genomic changes in hepatitis B virus (HBV) and evaluate their role in the development of hepatocellular carcinoma (HCC) in patients chronically infected with genotype C HBV.
METHODS: Two hundred and forty chronic hepatitis B (CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced using the direct sequencing method.
RESULTS: All of the subjects were infected with genotype C HBV. Out of 240 CHB patients, 25 (10%) had C1653T and 33 (14%) had T1753V mutation in X region; 157 (65%) had A1762T/G1764A mutations in BCP region, 50 (21%) had G1896A mutation in precore region and 67 (28%) had pre-S deletions. HCC occurred in 6 patients (3%). The prevalence of T1753V mutation was significantly higher in patients who developed HCC than in those without HCC. The cumulative occurrence rates of HCC were 5% and 19% at 10 and 15 years, respectively, in patients with T1753V mutant, which were significantly higher than 1% and 1% in those with wild type HBV (P < 0.001).
CONCLUSION: The presence of T1753V mutation in HBV X-gene significantly increases the risk of HCC development in patients chronically infected with genotype C HBV.
Core tip: In the present study, we determined the genomic changes in the X, S, basal core promoter (BCP), and precore regions of hepatitis B virus (HBV), and evaluate their role in the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with genotype C HBV. As the results, it was suggested that T1753V mutation in X region might significantly increase the risk of HCC development in CHB patients with genotype C HBV. Also, the BCP mutations might act in synergy with T1753V or G1896A mutation, and with pre-S deletion to promote the development of HCC in these patients.
