Publication Name	World Journal of Gastroenterology
Manuscript ID	25850
Country	South Korea

Received	2016-03-25 15:42
Peer-Review Started	2016-03-25 16:51
To Make the First Decision	2016-05-12 14:25
Return for Revision	2016-05-12 15:31
Revised	2016-05-17 08:28
Second Decision	2016-05-23 08:46
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief	2016-06-02 15:32
Articles in Press	2016-06-02 15:33
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript	2016-06-12 10:34
Publish the Manuscript Online	2016-06-21 18:11

ISSN	1007-9327 (print) and 2219-2840 (online)
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/
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Category	Virology
Manuscript Type	Topic Highlights
Article Title	X region mutations of hepatitis B virus related to clinical severity
Manuscript Source	Invited Manuscript
All Author List	Hong Kim, Seoung-Ae Lee and Bum-Joon Kim
Funding Agency and Grant Number	Funding Agency Grant Number National Research Foundation (NRF) grant of Ministry of Science, ICT and Future Planning, South Korea NRF-2015R1C1A1A02037267 Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea HI14C0955
Corresponding Author	Bum-Joon Kim, PhD, Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, South Korea. kbumjoon@snu.ac.kr
Key Words	Hepatitis B virus infection; Hepatitis B virus-X protein mutation; Hepatocellular carcinoma; Clinical severity
Core Tip	Of hepatitis B virus (HBV)-X protein (HBx) mutations related to clinical severity, the A1762T/G1764A BCP mutation is one of the most frequently encountered HBx mutations and plays a significant role in liver disease progression in chronic patients with HBV infections. It also further contributes to disease progression by inducing mutations of other HBx mutations related to clinical severity, such as G1386A/C (V5M/L), C1653T (H94Y), T1753V (I127V) and HBx C-terminal deletion or insertion. Moreover, T1753V (I127L,T,N,S) and C1653T (H94Y) mutations in the enhancer Ⅱ/BCP region and A1383C, G1386A/C (V5M/L) and C1485T (P38S) in the negative regulation domain are significantly related to severe types of liver diseases, including hepatocellular carcinoma. Furthermore, deletions or insertions affecting the C-terminal region of HBx may also contribute to the severity of the clinical outcome in chronic patients. In addition, our recent study indicated that a novel mutation type (X8Del) composed of an 8-bp deletion in the C-terminal region of the HBx could contribute to occult HBV infection in vaccinated Korean individuals via a reduced secretion of HBsAg and virions. Therefore, several distinct types of HBx mutations may contribute to HBV pathogenesis by regulating HBV replication or host genes related to cell homeostasis.
Publish Date	2016-06-21 18:11
Citation	Kim H, Lee SA, Kim BJ. X region mutations of hepatitis B virus related to clinical severity. World J Gastroenterol 2016; 22(24): 5467-5478
URL	http://www.wjgnet.com/1007-9327/full/v22/i24/5467.htm
DOI	http://dx.doi.org/10.3748/wjg.v22.i24.5467

Full Article (PDF)	WJG-22-5467.pdf
Full Article (Word)	WJG-22-5467.doc
Manuscript File	25850-Review.doc
Answering Reviewers	25850-Answering reviewers.pdf
Audio Core Tip	25850-Audio core tip.m4a
Conflict-of-Interest Disclosure Form	25850-Conflict-of-interest statement.pdf
Copyright License Agreement	25850-Copyright assignment.pdf
Approved Grant Application Form(s) or Funding Agency Copy of any Approval Document(s)	25850-Grant application form(s).pdf
Non-Native Speakers of English Editing Certificate	25850-Language certificate.pdf
Peer-review Report	25850-Peer-review(s).pdf
Scientific Misconduct Check	25850-Scientific misconduct check.pdf
Scientific Editor Work List	25850-Scientific editor work list.pdf