Home

search

Subjectguide
Journals
Books / Serials / Multimedia
Services
Services

Login for Subscribers
Logout

Sitemap
Help
Contacts


Logo







Vol. 49, No. 4, 2006 

View or print article as PDF (173 KB)   
 
Journal Home
Journal Content
Guidelines
Editorial Board
Aims and Scope
Subscriptions
Medline Abstract (ID 16407657)
Medline Related Articles
Download Citation
Cited In

Original Paper

Clinical Significance of the Genotype and Core Promoter/Pre-Core Mutations in Hepatitis B Virus Carriers
Satoru Hagiwaraa, Masatoshi Kudoa, Yasunori Minamia, Hobyung Chunga, Tatsuya Nakatania, Toyokazu Fukunagaa, Yukio Osakib, Yukitaka Yamashitac, Kozo Kajimurad

aDepartment of Gastroenterology and Hepatology, Kinki University, School of Medicine, Osaka;
bDepartment of Gastroenterology, Osaka Red Cross Hospital, Osaka;
cDepartment of Gastroenterology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, and
dDepartment of Gastroenterology, Kishiwada City Hospital, Osaka, Japan

Address of Corresponding Author

Intervirology 2006;49:200-206 (DOI: 10.1159/000090789)


 goto top of outline Key Words

  • Hepatitis B virus
  • Genotype
  • Core promoter
  • Pre-core

 goto top of outline Abstract

It has been shown that clinical and virological characteristics vary among hepatitis B virus (HBV) genotypes. In this study, we measured the virus level, disease severity, and presence or absence of core promoter (CP)/pre-core (PC) mutations in 241 HBV carriers, and investigated the clinical significance of measuring the HBV genotype. In genotype C HBV carriers, the proportion of hepatitis B e antigen (HBeAg)-positive patients was significantly higher than that in genotype B HBV carriers (0 vs. 34.4%, p < 0.05), and the virus level was higher (4.9 vs. 4.05 LGE/ml). In the genotype B HBV carriers, the incidence of PC mutation was significantly higher (69 vs. 34%, p < 0.05). In the genotype C HBV carriers, the incidence of CP mutation was significantly higher (13 vs. 78%, p < 0.05). We compared patients with the wild (W)/mutant (M) pattern in the CP/PC regions to those with the M/W pattern in the CP/PC regions among the genotype C HBV carriers. Both the proportion of HBeAg-positive patients (65.8 vs. 15.4%, p < 0.05) and the alanine aminotransferase (ALT) level (48 vs. 21.5 IU, p < 0.05) were higher in the patients with the M/W pattern in the CP/PC regions, and the disease severity was deteriorated. In conclusion, genotype B HBV may more frequently induce HBe seroconversion via PC mutation compared to genotype C HBV. Among the genotype C HBV carriers, hepatitis activity and the deterioration of the disease severity were significantly inhibited in the group in which PC mutation initially occurred, in comparison to the group in which CP mutation initially occurred.

Copyright © 2006 S. Karger AG, Basel


 goto top of outline References


1.
Hoofnagle JH, Dusheiko GM, Seeff LB, Jones EA, Waggoner JG, Bales ZB: Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med 1981;94:744-748.External Resources

2.
Realdi G, Alberti A, Rugge M, Bortolotti F, Rigoli AM, Tremolada F, Roul A: Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. Gastroenterology 1980;79:195-199.External Resources

3.
Lee WM: Hepatitis B virus infection. N Engl Med 1997;337:1733-1745.External Resources

4.
Lindh M, Horal P, Dhillon, AP, Norkrans G: Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis B. J Viral Hepatitis 2000;7:258-267.External Resources

5.
Mayerat C, Mantegani A, Frei PC: Does hepatitis B virus genotype influence the clinical outcome of HBV infection? J Viral Hepatitis 1999;6:299-304.External Resources

6.
Orito E, Mizokami M, Ina Y, Moriyama E, Kameshima N, Yamamoto M, Gojobori T: Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA 1989;86:7059-7062.External Resources

7.
Norder H, Courouce AM, Magnius LO: Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes. Virology 1994;198:489-503.External Resources

8.
Stuyver L, Gendt SD, Geyt CV, Zoulim F, Fried M, Schinazi RF, Rossau R: A new genotype of hepatitis B virus; complete genome and phylogenetic relatedness. J Gen Virol 2000;81:67-74.External Resources

9.
Okamoto H, Tsuda F, Sakugawa H, Sastrosoewignjo RI, Imai M, Miyakawa Y, Mayumi M: Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. J Gen Virol 1988;69:2575-2583.External Resources

10.
Magnius LO, Norder H: Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Intervirology 1995;38:24-34.External Resources

11.
Lindh M, Andersson AS, Gusdal A: Genotypes, nt 1,858 variants, and geographic origin of hepatitis virus - large-scale analysis using a new genotyping method. J Infect Dis 1997;175:1285-1293.External Resources

12.
Telenta PF, Poggio GP, Lopez JL, Gonzalez J, Lemberg A, Campos RH: Increased prevalence of genotype F hepatitis B virus isolated in Buenos Aires, Argentina. J Clin Microbiol 1997;35:1873-1875.External Resources

13.
Arauz-Ruiz P, Norder H, Visona KA, Magnius LO: Genotype F prevails in HBV infected patients of Hispanic origin in Central America and may carry the precore stop mutant. J Med Virol 1997;51:305-312.External Resources

14.
Kao JH, Chen PJ, Lai MY, Chen DS: Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000;118:554-559.External Resources

15.
Grandjacques C, Pradat P, Stuyver L, Chevallier M, Chevallier P, Pichoud C, Maisonnas M, Trepo C, Zoulim F: Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. J Hepatol 2000;33:430-439.External Resources

16.
Orito E, Mizokami M, Sakugawa H, Michitaka K, Ishikawa K, Ichida T, Okanoue T, Yotsuyanagi H, Iino S: A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV genotype Research Group. Hepatology 2001;33:218-223.External Resources

17.
Ding X, Mizokami M, Yao G, Xu B, Orito E, Ueda R, Nakanishi M: Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai, China. Intervirology 2001;44:43-47.External Resources

18.
Orito E, Ichida T, Sakugawa H, Sata M, Horiike N, Hino K, Okita K, Okanoue T, Iino S, Tanaka E, Suzuki K, Watanabe H, Hige S, Mizokami M: Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan. Hepatology 2001;34:590-594.External Resources

19.
Chu CJ, Hussain M, Lok AS: Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology 2002;122:1756-1762.External Resources

20.
Orito E, Mizokami M, Ina Y, Moriyama E, Kameshima N, Yamamoto M, Gojobori T: Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA 1989;86:7059-7062.External Resources

21.
Okamoto H, Yotsumoto S, Akahane Y, Yamanaka T, Miyazaki Y, Sugai Y, Tsuda F, Tanaka T, Miyakawa Y, Mayumi M: Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. J Virol 1990;64:1298-1303.External Resources

22.
Okamoto H, Tsuda F, Akahane Y, Sugai Y, Yoshiba M, Moriyama K, Tanaka T, Miyakawa Y, Mayumi M: Hepatitis B viruses with mutation in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. J Virol 1994;68:8102-8110.External Resources

23.
Ou JH: Molecular biology of hepatitis B virus e antigen. J Gastroenterol Hepatol 1997;12:178-187.External Resources

24.
Buckwold VE, Xu Z, Chen M, Yen TS, Ou JH: Effects of a naturally occurring mutation in the hepatitis virus basal core promoter on precore gene expression and viral replication. J Virol 1996;70:5845-5851.External Resources

25.
Moriyama K, Okamoto H, Tsuda F, Mayumi M: Reduced precore transcription and enhanced core-pregenome transcription of hepatitis B virus DNA after replacement of the precore-core promoter with sequences associated with e antigen-seronegative persistent infections. Virology 1996;226:269-280.External Resources

26.
Li J, Buckwold VE, Hon MW, Ou JH: Mechanism of suppression of hepatitis B virus precore RNA transcription by a frequent double mutation. J Virol 1999;73:1239-1244.External Resources

27.
Carman WF, Jacyna MR, Hadziyannis S, Karayiannis P, McGarvey MJ, Makris A: Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 1989;ii:588-591.External Resources

28.
Omata M, Ehata T, Yokosuka O, Hosoda K, Ohto M: Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis. N Engl J Med 1991;324:1699-1704.External Resources

29.
Sato S, Suzuki K, Akahane Y, Akamatsu K, Akiyama K, Yunomura K, Tsuda F, Tanaka T, Okamoto H, Miyakawa Y, Mayumi M: Hepatitis B virus strains with mutations in the core promoter in patients with fluminant hepatitis. Ann Intern Med 1995;122:241-248.External Resources

30.
Shiina S, Fujino H, Kawabe T, Tagawa K, Unuma T, Yoneyama M, Ohmori T, Suzuki S, Kurita M, Ohashi Y: Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Am J Gastroenterol 1991;86:872-875.External Resources

31.
Kao JH, Chen PJ, Lai MY, Chen DS: Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 2003;124:327-334.External Resources

32.
Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS: Hepatitis B genotypes and the response to interferon therapy. J Hepatol 2000;33:998-1002.External Resources

33.
Lindh M, Hannoun C, Dhillon AP, Norkrans G, Horal P: Core promoter mutations and genotypes in relation to viral replication and liver damage in East-Asian hepatitis B virus carriers. J Infect Dis 1999;179:775-782.External Resources


 goto top of outline Author Contacts

Masatoshi Kudo, MD, PhD
Department of Gastroenterology and Hepatology
Kinki University, School of Medicine, 377-2 Ohno-Higashi
Osaka-Sayama, Osaka 589-8511 (Japan)
Tel. +81 722 366 0221, Fax +81 722 367 2880, E-Mail m-kudo@med.kindai.ac.jp


 goto top of outline Article Information

Received: June 13, 2005
Accepted: June 20, 2005
Published online: January 11, 2006
Number of Print Pages : 7
Number of Figures : 5, Number of Tables : 3, Number of References : 33


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 49, No. 4, Year 2006 (Cover Date: May 2006)

Journal Editor: Liebert, U.G. (Leipzig)
ISSN: 0300-5526 (print), 1423-0100 (Online)

For additional information: http://www.karger.com/INT


 goto top of outline Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.

   


copyright  © 2009 S. Karger AG, Basel
  Last update: 12/5/2006