Hepatitis Viral Markers
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Hepatitis Viral Markers
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Hepatitis Viral Markers
- 1. Serology for viral hepatitis (HAV, HBV & HCV) Mohamed Sabry Ass. Lecturer of Internal Medicine Tanta Faculty of Medicine
- 2. Pathogenesis Clinical presentation Life cycle & Modes of transmission
- 3. Serology
- 4. Serology Hepatitis B viurs
- 5. Serology Hepatitis B viurs Test our knowledge
- 7. Anti-hepatitis A virus IgM: Positive at the time of onset of symptoms. Usually accompany the first rise in the alanine aminotransferase (ALT) level. This test is sensitive and specific. The results remain positive for 3-6 months after the primary infection and for as long as 12 months in 25% of patients.
- 8. Anti-hepatitis A virus IgG: Anti-HAV immunoglobulin G (IgG) appears soon after IgM and generally persists for many years. The presence of anti-HAV IgG in the absence of IgM indicates past infection or vaccination rather than acute infection. IgG provides protective immunity.
- 10. HBV: Structure
- 12. HBV: virus proteins & particles:
- 17. Basics: Deoxyribose nucleic acid (DNA) is the genetic material in all cells. It is a double helix structure made of nucleotides. Each nucleotide consists of a deoxyribose sugar, a phosphate group, and one of four bases: adenine, thymine, guanine and cytosine.
- 24. Protein products of the four genes S gene: HBsAg S region: Major protein S+preS2: Middle protein S+preS2+preS1:Large protein P gene: DNA polymerase Directs replication and repair of HBV DNA C gene: HBcAg HBeAg Translation begins with the C region. Translation begins at the preC region X gene: HBxAg It can transactivate transcription of cellular and viral genes It may contribute to carcinogenesis.
- 26. HBV: virus proteins & particles:
- 27. Protein products of the four genes S gene: HBsAg S region: Major protein S+preS2: Middle protein S+preS2+preS1:Large protein P gene: DNA polymerase Directs replication and repair of HBV DNA C gene: HBcAg HBeAg Translation begins with the C region. Translation begins at the preC region X gene: HBxAg It can transactivate transcription of cellular and viral genes It may contribute to carcinogenesis.
- 28. Viral proteins & particles:
- 29. Serology for HBV: Antigen Antibodies Hepatitis B Surface Antigen (HBsAg) Antibody to Hepatitis B Surface Antigen (Anti HBs) Hepatitis B Core Antigen (HBcAg) Antibody to Hepatitis B Core Antigen (Anti HBc IgM & Anti HBc) Hepatitis B ‘e’ Antigen (HBeAg) Antibody to Hepatitis B ‘e’ Antigen (Anti HBe)
- 30. Hepatitis B surface antigen (HBsAg): It is the envelop protein expressed on the outer surface of the virion and on the small spherical and tubular structures. It plays a major role in cell membrane attachment to initiate the infection process by binding to the hepatocyte plasma membrane C Seeger, et al. (2000): Mol Biol Rev.
- 31. HBsAg Common group reactive antigen (a). Several subtype specific antigens (d, y, w & r). HB isolates fall into at least 8 genotypes (A-H).
- 36. HBsAg
- 37. 1st virological marker detectable in serum usually between 8th and 12th weeks of infection HBsAg
- 38. 1st virological marker detectable in serum usually between 8th and 12th weeks of infection It preceeds elevation of aminotransferase activity and clinical symptoms by 2-6 weeks HBsAg
- 39. 1st virological marker detectable in serum usually between 8th and 12th weeks of infection It preceeds elevation of aminotransferase activity and clinical symptoms by 2-6 weeks HBsAg It remains elevated during the entire icteric or symptomatic phase of the disease.
- 40. 1st virological marker detectable in serum usually between 8th and 12th weeks of infection It preceeds elevation of aminotransferase activity and clinical symptoms by 2-6 weeks It remains elevated during the entire icteric or symptomatic phase of the disease. Typically, it disappeares 1-2 months after the onset of jaundice and rarely persists beyond 6 months. HBsAg
- 41. Strategies for prevention of HBV is based on providing susceptible persons with anti HBs. The protective antibodies Anti HBs
- 42. Duration of protection: almost indefinitely. A single booster may be required after 5 ys. HBsAg prepared by recombinant DNA technology
- 44. Not secreted and remains within hepatocytes Expressed on the surface of the nucleocapsid core HBcAg
- 45. HBV: virus proteins & particles:
- 46. Anti HBc IgM First antibody to appear. Indicates acute HBV infection.
- 47. May be the only marker in CORE WINDOW Anti HBcIgM Indicates acute HBV infection.
- 50. HBeAg Secreted into the circulation.
- 51. HBeAg Secreted into the circulation. HBeAg Accessory protein of HBV.
- 52. HBeAg Secreted into the circulation. HBeAg Accessory protein of HBV. HBeAg Not essential for replication in vivo
- 53. An index of viral replication, infectivity, severity of disease, and response to treatment
- 55. An index of viral replication, infectivity, severity of disease, and response to treatment High probability of progression to a chronic carrier state when HBeAg persists longer than 12 weeks. Pregnant women with HBeAg positive have a risk of transmission of virus to fetus is > 90%.
- 56. Anti HBe
- 57. Detectable when HBeAg disappears (12 – 16 wks) Anti HBe
- 58. Seroconversion to Anti HBe indicates resolution of infection. Anti HBe
- 59. Seroconversion may be associated with acute hepatitis like elevation of aminotransferase. Anti HBe
- 65. Basics Mutations are sudden changes in an organisms genetic material that result from alterations in DNA that can be induced or appear spontaneously.
- 68. Patients with precore mutation tend to have severe liver disease that progress more rapidly to cirrhosis. This is common in Mediteranean region and Europe. Clusters of fulminant HBV in Israel and Japan have been attributed to a common source of infection with a precore mutant.
- 69. HBV DNA A measure of virus replication in the liver and infectivity.
- 70. HBV DNA Monitoring treatment in patients with chronic HBV infection.
- 71. HBV DNA Loss of detectable HBV DNA is an earlier indicator of response to antiviral therapy than loss of HBeAg.
- 76. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + -
- 79. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity
- 80. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + -
- 84. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity
- 85. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity + - IgG - +
- 86. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity + - IgG - + Chronic HB, low infectivity
- 87. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity + - IgG - + HBeAg negative precore mutant HB
- 88. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity + - IgG - + Chronic HB, low infectivity HBeAg negative precore mutant HB + + +
- 89. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity + - IgG - + Chronic HB, low infectivity HBeAg negative precore mutant HB + + +
- 91. HBsAg Anti- HBsAg Anti-HBc HBeAg Anti-HBe Interpretation + - IgM + - Acute HB, High infectivity + - IgG + - Chronic HB, high infectivity + - IgG - + Chronic HB, low infectivity HBeAg negative precore mutant HB + + + + + HBsAg of one subtype and heterotypic antiHBs
- 92. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + +
- 95. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window)
- 96. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window) - - IgG - +
- 99. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window) - - IgG - + HB in the remote past
- 100. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window) - - IgG - + HB in the remote past Low level HB carrier - + IgG - +
- 103. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window) - - IgG - + HB in the remote past - + IgG - + Recovery from HB
- 104. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window) - - IgG - + HB in the remote past Low level HB carrier - + IgG - + Recovery from HB - + - - -
- 105. HBsAg Anti- HBs Anti- HBc HBeAg Anti-HBe Interpretation - - IgM + + Acute HB (window) - - IgG - + HB in the remote past Low level HB carrier - + IgG - + Recovery from HB - + - - - Immunization with HBsAg False positive
- 107. HCV •HCV antibody: • Generally used to diagnose hepatitis C infection. • Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
- 108. HCV • HCV-RNA: • Various techniques are available e.g. PCR. Cut-off: 1000 copies / ml • May be used to diagnose HCV infection in the acute phase. • However, its main use is in monitoring the response to antiviral therapy.
- 109. HCV RNA (PCR testing) Not a predictor of disease severity: a high viral load does not mean the liver disease is more severe, and a low viral load does not mean the patient is ok and does not need therapy! Helps predict response rate to treatment (lower means a higher chance of cure with therapy)
- 110. HCV: Genotyping: genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon therapy.
Editor's Notes
- Envelop
- Figure 304-3 Compact genomic structure of HBV. This structure, with overlapping genes, permits HBV to code for multiple proteins. The S gene codes for the “major” envelope protein, HBsAg. Pre-S1 and pre-S2, upstream of S, combine with S to code for two larger proteins, “middle” protein, the product of pre-S2 + S, and “large” protein, the product of pre-S1 + pre-S2 + S. The largest gene, P, codes for DNA polymerase. The C gene codes for two nucleocapsid proteins, HBeAg, a soluble, secreted protein (initiation from the pre-C region of the gene) and HBcAg, the intracellular core protein (initiation after pre-C). The X gene codes for HBxAg, which can transactivate the transcription of cellular and viral genes; its clinical relevance is not known, but it may contribute to carcinogenesis by binding to p53. being a virus of the family Hepadnaviridae, HBV is the smallest human DNA virus, carrying a genome only 3,200 nucleotides in length [4]. The partially double-stranded circular DNA harbors four overlapping open reading frames encoding the S (surface), C (core), P (polymerase), and X genes
- it precedes that of the core. It initiates an uncharacterized short upstream open reading frame (uORF), The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full length strand) and 1700–2800 nucleotides long (for the short length strand).
- The chemical convention of naming carbon atoms in the nucleotide sugar-ring numerically gives rise to a 5′-end and a 3′-end (usually pronounced "five prime end" and "three prime end").
- it precedes that of the core. It initiates an uncharacterized short upstream open reading frame (uORF), The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full length strand) and 1700–2800 nucleotides long (for the short length strand).
- Depending on where translation is initiated, three potential HBsAg products are synthesized.
- it precedes that of the core. It initiates an uncharacterized short upstream open reading frame (uORF), The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full length strand) and 1700–2800 nucleotides long (for the short length strand).
- Compared with the small spherical and tubular particles, the complete virions of HBV are enriched in the large protein.
- Depending on where translation is initiated, three potential HBsAg products are synthesized.
- Figure 41-1 Schematic diagram of HBV-related particles in serum and the associated antigens (in parentheses). The spheres and filaments consist of only hepatitis B surface glycoproteins (HBsAg). They are 20 nm in diameter and are 10,000-fold greater in concentration than the complete virion (Dane particle: 40 nm diameter).
- Figure 41-1 Schematic diagram of HBV-related particles in serum and the associated antigens (in parentheses). The spheres and filaments consist of only hepatitis B surface glycoproteins (HBsAg). They are 20 nm in diameter and are 10,000-fold greater in concentration than the complete virion (Dane particle: 40 nm diameter).
- HBsAg circulates in a wide array of particulate forms such as competent virions (42 nm, Dane particles), 20 nm diameter filaments of variable length, and 20–22 nm spherical defective particles, corresponding to empty viral envelopes. It exceeds virions by a variable factor of 102 – 105 and accumulates several hundred micrograms per ml of serum C Seeger, and W. S Mason, 2000Hepatitis B virus biologyMicrobiol Mol Biol Rev. 6415168
- A number of HBsAg subdeterminants have been identified. There is a common group reactive antigen (a). In addition, it may contain one of several subtype specific antigens (d, y, w & r). HB isolates fall into at least 8 genotypes (A-H).
- Genotypes vary in Antigen subtype e.g. genotype A (subtype adw) and genotype D (ayd). Geographic destribution e.g. genotype A & D predominate in USA and Europe and genotype B & C predominate in Asia. Clinical course e.g. genotype B is associated with less aggressive liver damage and less HCC as compared to genotype C .
- Genotypes vary in Antigen subtype e.g. genotype A (subtype adw) and genotype D (ayd). Geographic destribution e.g. genotype A & D predominate in USA and Europe and genotype B & C predominate in Asia. Clinical course e.g. genotype B is associated with less aggressive liver damage and less HCC as compared to genotype C .
- Genotypes vary in Antigen subtype e.g. genotype A (subtype adw) and genotype D (ayd). Geographic destribution e.g. genotype A & D predominate in USA and Europe and genotype B & C predominate in Asia. Clinical course e.g. genotype B is associated with less aggressive liver damage and less HCC as compared to genotype C .
- Genotypes vary in Antigen subtype e.g. genotype A (subtype adw) and genotype D (ayd). Geographic destribution e.g. genotype A & D predominate in USA and Europe and genotype B & C predominate in Asia. Clinical course e.g. genotype B is associated with less aggressive liver damage and less HCC as compared to genotype C .
- It is the 1st virological marker detectable in serum usually between 8th and 12th weeks of infection. It preceeds elevation of aminotransferase activity and clinical symptoms by 2-6 weeks. It remains elevated during the entire icteric or symptomatic phase of the disease. Typically, it disappeares 1-2 months after the onset of jaundice and rarely persists beyond 6 months.
- Patients with Genotype A are more likely to achieve clearence of viraemia and achieve HBsAg seroconversion spontaneously and in response to ttt
- Patients with Genotype A are more likely to achieve clearence of viraemia and achieve HBsAg seroconversion spontaneously and in response to ttt
- It is produced by yeast cells, into which the genetic code for HBsAg has been inserted Following the primary course of 3 vaccinations, a blood test may be taken after an interval of 1–4 months to establish if there has been an adequate response, which is defined as an anti-hepatitis B surface antigen (anti-Hbs) antibody level above 100 mIU/ml. Such a full response occurs in about 85–90% of individuals.[10] An antibody level between 10 and 100 mIU/ml is considered a poor response, and these people should receive a single booster vaccination at this time, but do not need further retesting.[10] People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past Hepatitis B infection, and given a repeat course of 3 vaccinations, followed by further retesting 1–4 months after the second course. Those who still do not respond to a second course of vaccination may respond to intradermal administration[11] or to a high dose vaccine[12] or to a double dose of a combined Hepatitis A and B vaccine.[13] Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.[10] Poor responses are mostly associated with being over the age of 40 years, obesity and smoking,[14] and also in alcoholics, especially if with advanced liver disease.[15] Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine.[10] At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.[16] It is now believed that the hepatitis B vaccine provides indefinite protection. However, it was previously believed and suggested that the vaccination would only provide effective cover of between five and seven years,[17][18] but subsequently it has been appreciated that long-term immunity derives from immunological memory which outlasts the loss of antibody levels and hence subsequent testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals.[19][20] Hence with the passage of time and longer experience, protection has been shown for at least 25 years in those who showed an adequate initial response to the primary course of vaccinations,[21] and UK guidelines now suggest that for initial responders who require ongoing protection, such as for healthcare workers, only a single booster is advocated at 5 years.[10]
- Nucleocapsid proteins are coded for by the C gene which has 2 initiation codons. Hepatitis B core antigen (HBcAg) is the antigen expressed on the surface of the nucleocapsid core, produced when translation begins with the core region. It is not secreted and remains within hepatocytes and exported only after being enveloped with HBsAg
- Compared with the small spherical and tubular particles, the complete virions of HBV are enriched in the large protein.
- Individuals tested within 72 hours after administration of vaccine may test as positive.
- Individuals tested within 72 hours after administration of vaccine may test as positive.
- Only test to assess presence of protective immunity after immunization with Hepatitis B vaccine. Levels of > 10 mIU / ml are protective. Positive result in individuals with recent acute HBV infection indicates convalescence. Some cases of Chronic HBV infection may have both HBsAg and Anti HBs. These antibodies are heterotypic and likely not protective.
- Only test to assess presence of protective immunity after immunization with Hepatitis B vaccine. Levels of > 10 mIU / ml are protective. Positive result in individuals with recent acute HBV infection indicates convalescence. Some cases of Chronic HBV infection may have both HBsAg and Anti HBs. These antibodies are heterotypic and likely not protective.
- Only test to assess presence of protective immunity after immunization with Hepatitis B vaccine. Levels of > 10 mIU / ml are protective. Positive result in individuals with recent acute HBV infection indicates convalescence. Some cases of Chronic HBV infection may have both HBsAg and Anti HBs. These antibodies are heterotypic and likely not protective.
- H. S Chen, et al1992The precore region of an avian hepatitis B virus is not required for viral replication. J Virol. 66956824 C Chang, et al1987Expression of the precore region of an avian hepatitis B virus is not required for viral replication.J Virol 611033225 MariaKuttikan Jayalakshmi, Narayanan Kalyanaraman and Ramasamy Pitchappan (2013). Hepatitis B Virus Genetic Diversity: Disease Pathogenesis, Viral Replication, Dr. German Rosas-Acosta (Ed.), ISBN: 978-953-51-1055-2, InTech, DOI: 10.5772/53818. Available from: http://www.intechopen.com/books/viral-replication/hepatitis-b-virus-genetic-diversity-disease-pathogenesis Hepatitis B e antigen (HBeAg) produced when translation begins at the precore region and it is secreted into the circulation. HBeAg is an accessory protein of HBV, not essential for replication in vivo but important for natural infection.
- High probability of progression to a chronic carrier state when HBeAg persists longer than 12 weeks. Correlates well with the level of infectivity, the quantity of virus present and the presence of viral DNA polymerase in the serum. This antigen has been used clinically as an index of viral replication, infectivity, severity of disease, and response to treatment
- Secreted HBeAg has an immunoregulatory function in utero by establishing T cell tolerance to HBeAg and HBcAg, which may predispose neonates born to HBV-infected mothers to develop persistent HBV infection. Milich et al., further demonstrated an immunomodulatory role of HBeAg in antigen presentation and recognition by CD4+ cells. D. R Milich, 1999Do T cells "see" the hepatitis B core and e antigens differently? Gastroenterology. 11637658 D. R Milich, et al1998The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid:a mechanism for persistence. J Immunol.1604201321 D. R Milich, et al1993Role of T-cell tolerance in the persistence of hepatitis B virus infection. J Immunol Emphasis Tumor Immunol. 14322633D. R Milich, et al1990Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci U S A. 87176599603
- Detectable when HBeAg disappears (12 – 16 wks). Seroconversion to Anti HBe indicates resolution of infection. In most cases this seroconversion is associated with acute hepatitis like elevation of aminotransferase. This may reflect cell mediated immune clearence of virus infected hepatocytes.
- In HBV genotype A, cytosine is present at position 1858 (C-1858) precluding the selection of the G1896A mutation (Figure 2) (15). This explains the low frequency of precore mutants in Northern Europe, North America, and parts of Africa where genotype A predominates (16) In contrast, the non- A HBV genotypes (B, C, D, and E) harbor thymidine at the same position (T-1858), which pairs with A at 1896 (16). Thus, precore mutants prevail in the Mediterranean where non-A genotypes, particularly D, are predominant(17;18). Lindh M, AnderssonAS, Gusdal A: Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus--largescale analysis using a new genotyping method. J. Infect. Dis. 175: 1285-1293, 1997 [pubmed] Laras A, Koskinas J, Avgidis K, et al: Incidence and clinical significance of hepatitis B virus precore gene translation initiation mutations in e antigen-negative patients. J. Viral Hepat 5: 241-248, 1998 [pubmed] Bozdayi AM, Bozkaya H, Turkyilmaz A, et al: Polymorphism of precore region of hepatitis B virus DNA among patients with chronic HBV infection in Turkey. Infection 27: 357-360, 1999 [pubmed] Amini-Bavil-Olyaee S, Sarrami-Forooshani R, Mahboudi F, et al: Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients. J. Med. Virol. 75: 227-234, 2005 [pubmed
- Figure 304-3 Compact genomic structure of HBV. This structure, with overlapping genes, permits HBV to code for multiple proteins. The S gene codes for the “major” envelope protein, HBsAg. Pre-S1 and pre-S2, upstream of S, combine with S to code for two larger proteins, “middle” protein, the product of pre-S2 + S, and “large” protein, the product of pre-S1 + pre-S2 + S. The largest gene, P, codes for DNA polymerase. The C gene codes for two nucleocapsid proteins, HBeAg, a soluble, secreted protein (initiation from the pre-C region of the gene) and HBcAg, the intracellular core protein (initiation after pre-C). The X gene codes for HBxAg, which can transactivate the transcription of cellular and viral genes; its clinical relevance is not known, but it may contribute to carcinogenesis by binding to p53. being a virus of the family Hepadnaviridae, HBV is the smallest human DNA virus, carrying a genome only 3,200 nucleotides in length [4]. The partially double-stranded circular DNA harbors four overlapping open reading frames encoding the S (surface), C (core), P (polymerase), and X genes
- In HBV genotype A, cytosine is present at position 1858 (C-1858) precluding the selection of the G1896A mutation (Figure 2) (15). This explains the low frequency of precore mutants in Northern Europe, North America, and parts of Africa where genotype A predominates (16) In contrast, the non- A HBV genotypes (B, C, D, and E) harbor thymidine at the same position (T-1858), which pairs with A at 1896 (16). Thus, precore mutants prevail in the Mediterranean where non-A genotypes, particularly D, are predominant(17;18). Lindh M, AnderssonAS, Gusdal A: Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus--largescale analysis using a new genotyping method. J. Infect. Dis. 175: 1285-1293, 1997 [pubmed] Laras A, Koskinas J, Avgidis K, et al: Incidence and clinical significance of hepatitis B virus precore gene translation initiation mutations in e antigen-negative patients. J. Viral Hepat 5: 241-248, 1998 [pubmed] Bozdayi AM, Bozkaya H, Turkyilmaz A, et al: Polymorphism of precore region of hepatitis B virus DNA among patients with chronic HBV infection in Turkey. Infection 27: 357-360, 1999 [pubmed] Amini-Bavil-Olyaee S, Sarrami-Forooshani R, Mahboudi F, et al: Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients. J. Med. Virol. 75: 227-234, 2005 [pubmed
- Patients with precore mutation are unable to secrete HBeAg and tend to have severe liver disease that progress more rapidly to cirrhosis. Clusters of fulminant HBV in Israel and Japan have been attributed to a common source of infection with a precore mutant. This is common in Mediteranean region and Europe.
- Quantification is done only for genotypes 1, 4, 5 and 6. For genotypes 2 and 3 only Qualitative analysis is done.