1. HBV Factors and Clinical Outcomes M Omata

2. Genotypes in China and Japan

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

4. North East Asia West Asia B and C D

5. Any Difference Between B and C

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

7. As with Flares Years eAg Seroconversion ALT

8. HBeAg Seroconversion When Induced Naturally?

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

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

11. SE Livingston Gastroenterology 2007 in press GenotypeNo. of patients Age at time of HBeAg clearance A3419 B620 C3648 D30518 F12616 Clearance of HBeAg in Alaskan natives

12. Genotype C is Late Seroconverter

13. Relation to Liver Diseases

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

15. Age of HCC and Genotypes 20’s30’s40’s50’s Orito et al. Hepatology 2001 60’s>60 No. of Pt. 40 20 B C B C n=117 Ages

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

17. Interferon Effect and Genotypes

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

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

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

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

22. How About Response To Nucs ?

23. Nuc and Genotype Kobayashi M, J Med Virol. 2006 0 20 40 60 80 100 0244896144>192 Weeks HBV DNA Cleared(%) 84% 76% 47% Genotype C (449) Genotype B (38)

24. How about Human Genotype ? Host Factors

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

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

27. Factors Viral Human Genotypes

28. Adjusted for HBV genotype and baseline ALT and HBV DNA 33628824019214496480 80 60 40 20 0 AA AG/GG P=0.018 HBeAg Seroconversion (%) weeks IL28B PEG-IFN induced HBeAg & HBsAg Response Sonneveld et al. Gastroenterology 2012 AG/GG AA P=0.042 33628824019214496480 10 8 6 4 2 0 HBsAg Seroclearance (%) weeks N=205

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

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

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

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

34. 19792012 3000 nt 3000000000 nt

35. Central/Kita Hospitals

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

37. 劇症肝炎 Pre-core Mutant Omata M N Engl J Med 1991;324:1699-1704 Pre-core Mutant 7/9Fulminant 0/10Acute Immediate Suppression of Virus Replication Badly Needed 6 ４歳女性 Omata K

38. NanoPore