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HBV Factors and Clinical Outcomes M Omata

HBV Factors and Clinical Outcomes M Omata. Genotypes in China and Japan. West Asia. North East Asia. Miyakawa Y et al. Intervirology 2003. North East Asia. B and C. D. West Asia. Any Difference Between B and C. Born Infected. Natural Course HBV Infection. HBeAg-positive. ALT.

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HBV Factors and Clinical Outcomes M Omata

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  1. HBV Factors and Clinical Outcomes M Omata

  2. Genotypes in China and Japan

  3. West Asia North East Asia Miyakawa Y et al. Intervirology 2003

  4. North East Asia B and C D West Asia

  5. Any Difference Between B and C

  6. Born Infected Natural Course HBV Infection HBeAg-positive ALT Years

  7. eAg Seroconversion As with Flares ALT Years

  8. HBeAgSeroconversion When Induced Naturally?

  9. HBV This Timing of Seroconversion Varies Any Differences among Genotypes ?

  10. Genotypes & Seroconversion BJ McMahon 1158 Eskimos for 20.5 years GASTROENTEROLOGY 2007

  11. Clearance of HBeAg in Alaskan natives SE Livingston Gastroenterology 2007 in press

  12. Genotype C is Late Seroconverter

  13. Relation to Liver Diseases

  14. Genotype and HCC 39/803 (4.9%) Genotype B Genotype C 40/358 (11.1%) Yang HI, J Natl Cancer Inst 2008

  15. Age of HCC and Genotypes B No. of Pt. C 40 n=117 C 20 B 20’s 30’s 40’s 50’s 60’s >60 Ages Orito et al. Hepatology 2001

  16. Genotype C The longer period of eAg-pos/high viral load May Bring more Patietns To HCC

  17. Interferon Effect and Genotypes

  18. e Loss & Seroconversion Percent Yrs Post-Peg IFN Wong VW, et al. Hepatology. 2010;51:1945-1953

  19. Interferon Therapy Genotype & HBeAg Clearance 32% 13/41 14% 9/66 Genotype C Genotype B Wai CT, Hepatology 2002

  20. Interferon & HBsAg Clearance 80 70 Follow-up 3 years 60 50 Proportion of initial responders(%) 40 14% 0% 30 20 10 0 Genotype B (n=7) Genotype C (n=9) HBsAg negative Buster EH, Gastroenterology. 2008

  21. Response to PEG-IFN in HBeAg positive CHB HBeAg Loss HBsAg Loss 2 1 47% 44% 50 18 14% 40 15 28% 25% 30 12 9% Percentage of patients (%) 9 20 Percentage of patients (%) 6 3% 10 2% 3 0 0 B n=23 C n=39 D n=103 B n=23 C n=39 D n=103 A n=90 A n=90 1 Janssen, Lancet 2005; 2Flink, Am J Gastro 2006

  22. How About Response To Nucs ?

  23. Nuc and Genotype 100 Genotype B (38) 84% 80 76% Genotype C (449) 60 HBV DNA Cleared(%) 47% 40 20 0 0 24 48 96 144 >192 Weeks Kobayashi M, J Med Virol. 2006

  24. Host Factors How about Human Genotype ?

  25. IL28B in HBV infection ? In hepatitis C, Strong Association IL28B gene and Response to PEG-IFN + RBV

  26. IL28B Genotype Distribution AA (and CC) predominates in Asians p<0.001 AA AA AG AG GG GG Non-Asians (n=133) Asians (n=133) Sonneveld et al. Gastroenterology 2012 in press

  27. Factors Viral Human Genotypes

  28. IL28B PEG-IFN induced HBeAg & HBsAg Response N=205 Adjusted for HBV genotype and baseline ALT and HBV DNA 80 10 AA 8 P=0.018 60 AA HBeAg Seroconversion (%) HBsAg Seroclearance (%) 6 40 P=0.042 4 AG/GG 20 AG/GG 2 0 0 0 48 96 144 192 240 288 336 0 48 96 144 192 240 288 336 weeks weeks Sonneveld et al. Gastroenterology 2012

  29. We, Asian, may have been infected by Tougher Virus, but may have Favorable Genotype for Treatment But this is yet to be proven in larger Asian population And including more SNPs

  30. Studies for the Future Interacting “Genotypes” may answer many of un-answered questions In HBV infection

  31. a big step forward Nature Review GastroHepatol 2012;9:69-70

  32. a big step forward GWAS Whole Genome Sequencing Nature Review GastroHepatol 2012;9:69-70

  33. You can get 3 billion In a day Ion Proton 3 billion AGCT

  34. 1979 2012 3000000000nt 3000nt

  35. Central/Kita Hospitals

  36. Greatly appreciate your patience 謝謝 Prof Q Ning and Staff

  37. 劇症肝炎 6４歳女性 Omata K Pre-core Mutant Pre-core Mutant 7/9 Fulminant 0/10 Acute Immediate Suppression of Virus Replication Badly Needed OmataM N Engl J Med 1991;324:1699-1704

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