Journal Information
Vol. 16. Issue 1.
Pages 52-56 (January - February 2012)
Share
Share
Download PDF
More article options
Vol. 16. Issue 1.
Pages 52-56 (January - February 2012)
Open Access
Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations in HBV-infected Chinese patients with persistently normal alanine aminotransferase and low serum HBV-DNA levels
Visits
2772
Ming Shia,
Corresponding author
zhsh6655@sohu.com

Corresponding author at: 269 Guibai Road, Dalian 116031, Liaoning Province, China.
, Yong Zhanga, Jing Zhangb, Wei Liua, Lu Xinga
a Central Laboratory, No.6 Hospital of Dalian, Liaoning Province, China
b Department of Clinical Laboratory, Dalian Central Hospital, Liaoning Province, China
This item has received

Under a Creative Commons license
Article information
Abstract

Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP) mutants in the patients with persistently normal alanine aminotransferase (ALT) and low serum HBV-DNA levels are unclear. The aim of this study was to determine HBV genotypes, precore and BCP mutations, and their association with chronic hepatitis and liver fibrosis in HBV-infected patients with persistently normal ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real-time PCR were included in this study. HBV genotypes were determined by real-time PCR. The precore and BCP mutations were detected by sequencing. All the patients had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%) were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%), and A1762T (6.7%). The prevalence of precore mutation was significantly higher in genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01). There was no significant difference in the prevalence of BCP mutations between genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that old age (> 40 years) and BCP mutations were independent predictors of liver necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver necroinflammation and fibrosis in patients with persistently normal ALT and low serum HBV-DNA levels in northeast China.

Keywords:
Hepatitis B virus
Genotype
Mutation
Alanine transaminase
Full text is only aviable in PDF
References
[1.]
W.M. Lee.
Hepatitis B virus infection.
N Engl J Med, 337 (1997), pp. 1733-1745
[2.]
H. Okamoto, F. Tsuda, H. Sakugawa, et al.
Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes.
J Gen Virol, 69 (1988), pp. 2575-2583
[3.]
H. Norder, A.M. Courouce, P. Coursaget, et al.
Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes.
Intervirology, 47 (2004), pp. 289-309
[4.]
J.H. Kao, P.J. Chen, M.Y. Lai, et al.
Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B.
Gastroenterology, 118 (2000), pp. 554-559
[5.]
J.M. Sanchez-Tapias, J. Costa, A. Mas, et al.
Influence of hepatitis B virus genotypes on the long term outcome of chronic hepatitis B in Western patients.
Gastroenterology, 123 (2002), pp. 1848-1856
[6.]
M.F. Yuen, E. Sablon, D.K. Wong, et al.
Role of hepatitis B virus genotypes in chronic hepatitis B exacerbation.
Clin Infect Dis, 37 (2003), pp. 593-597
[7.]
J.H. Kao, N.H. Wu, P.J. Chen, et al.
Hepatitis B genotypes and the response to interferon therapy.
J Hepatol, 33 (2000), pp. 998-1002
[8.]
A. Bartholomeusz, S. Locarnini.
Hepatitis B virus mutants and fulminant hepatitis B: fitness plus phenotype.
Hepatology, 34 (2001), pp. 432-435
[9.]
T.J. Liang, K. Hasegawa, N. Rimon, et al.
A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis.
N Engl J Med, 324 (1991), pp. 1705-1709
[10.]
M.L. Funk, D.M. Rosenberg, A.S. Look.
World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants.
J Viral Hepat, 9 (2002), pp. 52-61
[11.]
H. Okamoto, F. Tsuda, Y. Akahane, et al.
Hepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen.
J Virol, 68 (1994), pp. 8102-8110
[12.]
H.L. Chan, M. Hussian, A.S. Lok.
Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion.
Hepatology, 29 (1999), pp. 976-984
[13.]
H.I. Yang, S.H. Yeh, P.J. Chen, et al.
Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma.
J Natl Cancer Inst, 100 (2008), pp. 1134-1143
[14.]
A.S. Lok, B.J. McMahon.
Chronic hepatitis B: update 2009.
Hepatology, 50 (2009), pp. 1-36
[15.]
W. Alazawi, G.R. Foster.
Advances in the diagnosis and treatment of hepatitis B.
Curr Opin Infect Dis, 21 (2008), pp. 508-515
[16.]
C.J. Chu, M. Hussain, A.S. Lok.
Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C.
Gastroenterology, 122 (2002), pp. 1756-1762
[17.]
H. Sumi, O. Yokosuka, N. Seki, et al.
Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease.
Hepatology, 37 (2003), pp. 19-26
[18.]
M. Shi, Y. Zhang, Y.H. Zhu, et al.
Comparison of real-time polymerase chain reaction with the COBAS Amplicor test for quantitation of hepatitis B virus DNA in serum samples.
World J Gastroenterol, 14 (2008), pp. 479-483
[19.]
S.H. Yeh, C.Y. Tsai, J.H. Kao, et al.
Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis.
J Hepatol, 41 (2004), pp. 659-666
[20.]
K.P. Batts, J. Ludwig.
Chronic hepatitis. An update on terminology and reporting.
Am J Surg Pathol, 19 (1995), pp. 1409-1417
[21.]
G.V. Papatheodoridis, E.K. Manesis, S. Manolakopoulos, et al.
Is there a meaningful serum HBV DNA cutoff level for therapeutic decisions in HBeAg-negative chronic hepatitis b virus infection?.
Hepatology, 48 (2008), pp. 1451-1459
[22.]
M. Omata, T. Ehata, O. Yokosuka, et al.
Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis.
N Engl J Med, 324 (1991), pp. 1699-1704
[23.]
J.H. Kao, P.J. Chen, M.Y. Lai, et al.
Basal promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers.
Gastroenterology, 124 (2003), pp. 327-334
[24.]
K. Hayashi, Y. Katano, Y. Takeda, et al.
Association of hepatitis B virus subgenotypes and basal core promoter/precore region variants with the clinical features of patients with acute hepatitis.
J Gastroenterol, 43 (2008), pp. 558-564
[25.]
F.D. Victoria, M.C. Oliveira, M.B. Victoria, et al.
Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia.
Braz J Infect Dis, 12 (2008), pp. 27-37
[26.]
M.F. Yuen, Y. Tanaka, I.O. Ng, et al.
Hepatic necroinflammation and fibrosis in patients with genotypes Ba and C, core-promoter and precore mutations.
J Viral Hepat, 12 (2005), pp. 513-518
[27.]
E. Orito, M. Mizokami, H. Sakugawa, et al.
A case-control study for clinical and molecular biological dirrerences between hepatitis B viruses of genotypes B and C, Japan HBV Genotype Research Group.
Hepatolgy, 33 (2001), pp. 218-223
[28.]
M.F. Yuen, E. Sablon, H.J. Yuan, et al.
The relationship between the development of precore and core promoter mutations and HBeAg seroconversion in chronic hepatitis B.
J Infect Dis, 186 (2002), pp. 1335-1338
[29.]
V.E. Buchwold, Z. Xu, T.S. Yen, et al.
Effects of a frequent double-nucleotide basal core promoter mutation and its putative single-nucleotide precurcor mutations on hepatitis B virus gene expression and replication.
J Gen Virol, 78 (1997), pp. 2055-2065
[30.]
K. Moriyama, H. Okamoto, F. Tusda, et al.
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, 226 (1996), pp. 269-280
Copyright © 2011. Elsevier Editora Ltda.. All rights reserved
The Brazilian Journal of Infectious Diseases
Article options
Tools