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Semin Liver Dis 2006; 26(2): 097-103
DOI: 10.1055/s-2006-939756
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Serological and Molecular Diagnosis

Scott Bowden1
  • 1Victorian Infectious Diseases Reference Laboratory, North Melbourne, and Department of Microbiology, Monash University, Clayton, Victoria, Australia
Further Information

Publication History

Publication Date:
03 May 2006 (online)

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ABSTRACT

The development of serological assays to detect hepatitis B surface antigen (HBsAg) has played a major role in the diagnosis of hepatitis B virus (HBV) infection. With other hepatitis B serological assays, a diagnosis of acute or chronic HBV infection, past infection, or successful vaccination can be determined. However, serological profiles can at times be atypical or ambiguous. Some of these difficulties may be overcome by HBV DNA testing, which may elucidate an individual's true hepatitis B status. In addition, quantification of HBV DNA provides a means of monitoring the effectiveness of antiviral therapy and detecting the early development of antiviral drug resistance. Molecular diagnostics are also being applied to HBV-infected liver tissue. The use of molecular techniques to quantify intrahepatic HBV DNA and other key HBV replicative intermediates may provide additional options for monitoring and predicting treatment efficacy, but such assays require further validation before they can be used routinely.

KEYWORDS

Hepatitis B serology - hepatitis B virus DNA - HBV DNA amplification assays

REFERENCES

  • 1 Blumberg B S, Alter H J, Visnich S A. “New” antigen in leukemia sera.  JAMA. 1965;  191 541-546
    CrossrefPubMedSearch in Google Scholar
  • 2 Szmuness W, Stevens C E, Zang E A, Harley E J, Kellner A. A controlled clinical trial of the efficacy of the hepatitis B vaccine (Heptavax B): a final report.  Hepatology. 1981;  1 377-385
    PubMedSearch in Google Scholar
  • 3 Dane D S, Cameron C H, Briggs M. Virus-like particles in serum of patients with Australia-antigen-associated hepatitis.  Lancet. 1970;  1 695-698
    PubMedSearch in Google Scholar
  • 4 Hollinger FBLT. Hepatitis B Virus. 4th ed. Philadelphia; Lippincott Williams and Wilkins 2001
    Search in Google Scholar
  • 5 Milich D R, Jones J E, Hughes J L, Price J, Raney A K, McLachlan A. Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero?.  Proc Natl Acad Sci U S A. 1990;  87 6599-6603
    PubMedSearch in Google Scholar
  • 6 Harrison T J. Hepatitis B virus: molecular virology and common mutants.  Semin Liver Dis. 2006;  26 87-96
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Lok A S, Akarca U, Greene S. Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal.  Proc Natl Acad Sci U S A. 1994;  91 4077-4081
    PubMedSearch in Google Scholar
  • 8 Okamoto H, Tsuda F, Akahane Y 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. 1994;  68 8102-8110
    PubMedSearch in Google Scholar
  • 9 Sherlock S. Virus hepatitis B, A, non-A, non-B.  J Hepatol. 1989;  8 254-258
    CrossrefPubMedSearch in Google Scholar
  • 10 Fagan E A, Williams R. Fulminant viral hepatitis.  Br Med Bull. 1990;  46 462-480
    PubMedSearch in Google Scholar
  • 11 Biswas R, Tabor E, Hsia C C et al.. Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection.  Transfusion. 2003;  43 788-798
    CrossrefPubMedSearch in Google Scholar
  • 12 Pfeifer K, Pelzer C, Coleman P, Pope M, Kapprell H P. Early detection of hepatitis B surface antigen-prototype of a new fully automated HBsAg microparticle enzyme immunoassay (MEIA).  Clin Lab. 2003;  49 161-166
    PubMedSearch in Google Scholar
  • 13 Bowden S. Laboratory Diagnosis of Hepatitis B Infection. 1st ed. London; International Medical Press 2002
    Search in Google Scholar
  • 14 Wieland S F, Chisari F V. Stealth and cunning: hepatitis B and hepatitis C viruses.  J Virol. 2005;  79 9369-9380
    CrossrefPubMedSearch in Google Scholar
  • 15 Laras A, Koskinas J, Hadziyannis S J. In vivo suppression of precore mRNA synthesis is associated with mutations in the hepatitis B virus core promoter.  Virology. 2002;  295 86-96
    CrossrefPubMedSearch in Google Scholar
  • 16 Hadziyannis S J, Papatheodoridis G V, Vassilopoulos D. Treatment of HBeAg-negative chronic hepatitis B.  Semin Liver Dis. 2003;  23 81-88
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Sjogren M, Hoofnagle J H. Immunoglobulin M antibody to hepatitis B core antigen in patients with chronic type B hepatitis.  Gastroenterology. 1985;  89 252-258
    PubMedSearch in Google Scholar
  • 18 Tassopoulos N C, Papatheodoridis G V, Kalantzakis Y et al.. Differential diagnosis of acute HBsAg positive hepatitis using IgM anti-HBc by a rapid, fully automated microparticle enzyme immunoassay.  J Hepatol. 1997;  26 14-19
    CrossrefPubMedSearch in Google Scholar
  • 19 Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”?.  Hepatology. 2001;  34 194-203
    CrossrefPubMedSearch in Google Scholar
  • 20 Hu K Q. Occult hepatitis B virus infection and its clinical implications.  J Viral Hepat. 2002;  9 243-257
    CrossrefPubMedSearch in Google Scholar
  • 21 Saldanha J, Gerlich W, Lelie N, Dawson P, Heermann K, Heath A. An international collaborative study to establish a World Health Organization international standard for hepatitis B virus DNA nucleic acid amplification techniques.  Vox Sang. 2001;  80 63-71
    CrossrefPubMedSearch in Google Scholar
  • 22 Yu M W, Yeh S H, Chen P J et al.. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men.  J Natl Cancer Inst. 2005;  97 265-272
    CrossrefPubMedSearch in Google Scholar
  • 23 Nowak M A, Bonhoeffer S, Hill A M, Boehme R, Thomas H C, McDade H. Viral dynamics in hepatitis B virus infection.  Proc Natl Acad Sci U S A. 1996;  93 4398-4402
    CrossrefPubMedSearch in Google Scholar
  • 24 Zeuzem S, de Man R A, Honkoop P, Roth W K, Schalm S W, Schmidt J M. Dynamics of hepatitis B virus infection in vivo.  J Hepatol. 1997;  27 431-436
    CrossrefPubMedSearch in Google Scholar
  • 25 Lewin S R, Ribeiro R M, Walters T et al.. Analysis of hepatitis B viral load decline under potent therapy: complex decay profiles observed.  Hepatology. 2001;  34 1012-1020
    CrossrefPubMedSearch in Google Scholar
  • 26 Locarnini S, Hatzakis A, Heathcote J et al.. Management of antiviral resistance in patients with chronic hepatitis B.  Antivir Ther. 2004;  9 679-693
    PubMedSearch in Google Scholar
  • 27 Pawlotsky J M. Molecular diagnosis of viral hepatitis.  Gastroenterology. 2002;  122 1554-1568
    PubMedSearch in Google Scholar
  • 28 Newbold J E, Xin H, Tencza M et al.. The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes.  J Virol. 1995;  69 3350-3357
    PubMedSearch in Google Scholar
  • 29 Bock C T, Schranz P, Schroder C H, Zentgraf H. Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell.  Virus Genes. 1994;  8 215-229
    CrossrefPubMedSearch in Google Scholar
  • 30 Summers J, Mason W S. Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate.  Cell. 1982;  29 403-415
    CrossrefPubMedSearch in Google Scholar
  • 31 Seeger C, Mason W S. Hepatitis B virus biology.  Microbiol Mol Biol Rev. 2000;  64 51-68
    CrossrefPubMedSearch in Google Scholar
  • 32 Tuttleman J S, Pourcel C, Summers J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells.  Cell. 1986;  47 451-460
    CrossrefPubMedSearch in Google Scholar
  • 33 Wu T T, Coates L, Aldrich C E, Summers J, Mason W S. In hepatocytes infected with duck hepatitis B virus, the template for viral RNA synthesis is amplified by an intracellular pathway.  Virology. 1990;  175 255-261
    CrossrefPubMedSearch in Google Scholar
  • 34 Jun-Bin S, Zhi C, Wei-Qin N, Jun F. A quantitative method to detect HBV cccDNA by chimeric primer and real-time polymerase chain reaction.  J Virol Methods. 2003;  112 45-52
    CrossrefPubMedSearch in Google Scholar
  • 35 Kock J, Theilmann L, Galle P, Schlicht H J. Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus.  Hepatology. 1996;  23 405-413
    PubMedSearch in Google Scholar
  • 36 Sung J J, Wong M L, Bowden S et al.. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy.  Gastroenterology. 2005;  128 1890-1897
    CrossrefPubMedSearch in Google Scholar
  • 37 Werle-Lapostolle B, Bowden S, Locarnini S et al.. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy.  Gastroenterology. 2004;  126 1750-1758
    CrossrefPubMedSearch in Google Scholar
  • 38 Hui C K, Bowden S, Jackson K et al.. Clinical significance of intrahepatic hepatitis B virus covalently closed circular DNA in chronic hepatitis B patients who received cytotoxic chemotherapy.  Blood. 2005;  105 2616-2617
    CrossrefPubMedSearch in Google Scholar

Scott BowdenPh.D. 

Victorian Infectious Diseases Reference Laboratory

10 Wreckyn Street, North Melbourne, Victoria 3051, Australia