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Correlation of HBsAg and HBV DNA Michael Chudy, Paul-Ehrlich-Institut SoGAT XVIII, Bethesda MD

PEI. Correlation of HBsAg and HBV DNA Michael Chudy, Paul-Ehrlich-Institut SoGAT XVIII, Bethesda MD 24-25 May 2005. HBsAg and HBV DNA. Most sensitive HBsAg assay detects 0.01 ng/ml (PEI HBsAg standard; ad) HBsAg cut-off correspond to HBV DNA 114 IU/ml (WHO DNA standard)

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Correlation of HBsAg and HBV DNA Michael Chudy, Paul-Ehrlich-Institut SoGAT XVIII, Bethesda MD

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  1. PEI Correlation of HBsAg and HBV DNA Michael Chudy, Paul-Ehrlich-Institut SoGAT XVIII, Bethesda MD 24-25 May 2005

  2. HBsAg and HBV DNA • Most sensitive HBsAg assay detects0.01 ng/ml (PEI HBsAg standard; ad) • HBsAg cut-off correspond to HBV DNA • 114 IU/ml (WHO DNA standard) • 461 copies/ml (five SC panels; ZeptoMetrix) Good correlation to published data from Biswas et al.; Transfusion 43:788-798 (2003)

  3. Virus and HBsAg Particles

  4. HBsAg reactive polypeptides • Most sensitive ELISA detects 10 pg HBsAg/ml • Virion-HBsAg • One HBV particle: 20 ag HBsAg* • 10 pg HBsAg correspond to about 500,000 HBV particles • 500 particles/ml (HBsAg cutoff of SC panels) vs. 500,000 HBV particles/ml • Viral surface antigen reactive polypeptides • Virion envelope • Incomplete viral forms • Excessive incomplete viral forms are present (about 1:1,000) *Average numbers of molecules of LHBs, MHBs, and SHBs: 30, 30, and 350, respectively; Calculation correlate well with data presented by Prof. Gerlich (EPFA meeting 2002)

  5. Correlation of HBsAg and HBV DNA Is that true for all geno-/subtypes, stages … of HBV infection? Can HBV NAT replace the HBsAg testing in blood donors?

  6. HBsAg and HBV DNA • HBV DNA: reverse transcription from 3.35 kb pre-genomic mRNA • HBsAg forms translated from LHBs 2.4 kb mRNA MHBs/SHBs 2.1 kb mRNA • Level of regulation • Transcription • Post-transcription e.g. Transport of unspliced mRNAs from nucleus to cytoplasm • Cellular factors

  7. Ratio of total HBsAg to Virion-HBsAgat different HBV stages • Early period of HBV infection • Genotype A • Genotype G • Chronic HBV infection

  8. 1:490 1:200 1:1,100 1:730 1:2,200 Total HBsAg/Virion-HBsAg ratio in samples of SC panel PHM911 (BBI)# 21 d #data performed in 1995

  9. HBV genotype G • Only few infections are known (all co-infections with genotype A) • First report of HBV infection and transmission based exclusively on genotype G (2003 in Germany) • No escape variant (subtype adw2) • HBeg minus variant • Studies were performed in cooperation with the Institute of • Transfusion Medicine and Immunohematology, GRC, • JW Goethe University, Frankfurt (WK Roth and co-workers)

  10. HBV transmission exclusively by genotype G-virus

  11. Virion-HBsAg/total HBsAg ratio in genotype G Sample from R3 (2003-09-23) with about 9 Mio cps/ml (positive for HBsAg, negative for anti-HBc, HBeAg/anti-HBe) • Titration in Prism HBsAg test • Virus concentration at HBsAg cut-off:24,000 copies/ml • Ratio of virion-HBsAg to total HBsAg of 1:20 • vs. 1:1,000 and more in genotype A samples of early HBV infection • Significant decrease of excessive HBsAg in infection with genotype G

  12. HBsAg and HBV DNA in chronic HBV infection • Lack of correlation between HBsAg and HBV DNA in HBsAg/anti-HBc positive tested samples (Kuhns et al. 2004, Transfusion 44,1332-1339)

  13. HBsAg and HBV DNA in chronic HBV carriers • Investigation of 106 chronic carriers tested positive for HBsAg, anti-HBc, and anti-HBe • Only 84% (89/106) HBV NAT reactive with the Procleix Ultrio Assay (Gen-Probe) • s/co >20 5x • s/co 15-20 65x • s/co 10-15 9x • s/co 5-10 7x • s/co <5 3x • No correlation to s/co values of HBsAg test (Prism)

  14. 17 HBsAg positive/HBV DNA negative samples of chronic HBV carriers

  15. Summary: Correlation ofHBsAg and HBV DNA • Virion-HBsAg of one particle (20 ag) correspond to one copy of HBV DNA • Significant excess of HBsAg particles in the early period of HBV infection (genotype A) • Variable ratio of Virion-HBsAg to total HBsAg in the course of infection (genotype A) • Genotype G infection shows a significant decrease in synthesis of incomplete viral forms • Lack of correlation between HBsAg and HBV DNA in chronic infection • HBsAg carrier (integrative phase) can be non-reactive by HBV NAT • Results indicate caution in any consideration of dropping HBsAg screening

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