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
- 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
- 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
- 4 Hollinger FBLT. Hepatitis B Virus. 4th ed. Philadelphia; Lippincott Williams and
Wilkins 2001
- 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
- 6
Harrison T J.
Hepatitis B virus: molecular virology and common mutants.
Semin Liver Dis.
2006;
26
87-96
- 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
- 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
- 9
Sherlock S.
Virus hepatitis B, A, non-A, non-B.
J Hepatol.
1989;
8
254-258
- 10
Fagan E A, Williams R.
Fulminant viral hepatitis.
Br Med Bull.
1990;
46
462-480
- 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
- 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
- 13 Bowden S. Laboratory Diagnosis of Hepatitis B Infection. 1st ed. London; International
Medical Press 2002
- 14
Wieland S F, Chisari F V.
Stealth and cunning: hepatitis B and hepatitis C viruses.
J Virol.
2005;
79
9369-9380
- 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
- 16
Hadziyannis S J, Papatheodoridis G V, Vassilopoulos D.
Treatment of HBeAg-negative chronic hepatitis B.
Semin Liver Dis.
2003;
23
81-88
- 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
- 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
- 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
- 20
Hu K Q.
Occult hepatitis B virus infection and its clinical implications.
J Viral Hepat.
2002;
9
243-257
- 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
- 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
- 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
- 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
- 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
- 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
- 27
Pawlotsky J M.
Molecular diagnosis of viral hepatitis.
Gastroenterology.
2002;
122
1554-1568
- 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
- 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
- 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
- 31
Seeger C, Mason W S.
Hepatitis B virus biology.
Microbiol Mol Biol Rev.
2000;
64
51-68
- 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
- 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
- 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
- 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
- 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
- 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
- 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
Scott BowdenPh.D.
Victorian Infectious Diseases Reference Laboratory
10 Wreckyn Street, North Melbourne, Victoria 3051, Australia