HCV. C C hepatitis C virus HCV HCV HCV HCV. Human genome project HCV. sustained viral response SVR transient viral response TVR non viral response NVR

Transkript

1 Vol. 24 No WAS IL28B hepatitis virus HV HV 7 8 HV HV 1 HV Peg IFN RBV Peg IFN RBV HV 2 80 HV ,4 HV HV HV Human genome project Peg IFN RBV HV 1 Peg IFN RBV sustained viral response SVR transient viral response VR non viral response NVR Masashi Mizokami

2 208 1 IFN Factor Feature HV genotype 1 ore70 R Q, H ore91 L M ISDR 0 wild SVR SVR Peg IFN RBV SVR VR VR NVR SVR Peg IFN RBV SVR VR 5, VR SVR HV HV NS5A interferon stimulated determination region ISDR interferon ribavirin resistance determining region IRRDR NVR NVR IRRDR Human genome project SNPs single nucleotide polymorphisms SNPs 1,000 SNPs SNPs SNPs SNPs HapMap 13 SNPs SNPs SNPs SNPs 14,15

3 Vol. 24 No IFN IL 28B Sensitive Resistant rs rs A rs rs rs rs A OR 95 I p value HV 2007 Peg IFN RBV Peg IFN RBV SNPs 6.0 array 90 SNPs enome wide association study WAS 62 SNPs SNPs Digiag2 16 VR SVR SVR & VR VR NVR NVR VR NVR 19 IL28B SNPs 17 SNPs p odds ratio OR 30 SNPs SNPs SNPs OR 11 p SNPs Peg IFN RBV OR SVR e OR 3.1 SNPs rs SNPs HV Peg IFN RBV SNPs Suppiah Rauch SNPs OR rs SNPs HapMap 4

4 210 3 WAS 4 Study e Suppiah anaka Region Northern America Northern Europe, Australia Japan Ancestry aucasian African Hispanic aucasian Japanese WAS size ase control SVR vs. non SVR SVR vs. non SVR SVR vs. non SVR SVR & VR vs. NVR HV genotype Significant SNPs rs p value OR 95 I SVR Sustained viral response, VR ransient viral response, NVR Non viral response, PE IFN Pegylated interferon alpha, RBV Ribavirin 4 2SNPs SNPs rs P value aucasians 0.99 D African 1.00 Hispanics 1.00 Peg IFN RBV 19 NR Peg IFN RBV 13 SVR WAS WAS HV Peg IFN RBV RBV VR SVR HV IL 28B Fellay 1,286 SNPs rs SNPs 20 Inosine triphosphatase IPA rs rs ,22 Fellay rs rs rs SNPs

5 Vol. 24 No IPA SNPs rs SNPs Rs Population European African Hispanic ombined European African Hispanic ombined MAF Independent p value MAF minor allele frequency 20 6 SNPs homas Rauch SNPs rs Population European African HV mono HV & HIV combined OR p value HV HV 30 20,23,24 homas e rs SNPs Rauch WAS HV SNPs SNPs rs HV IL28B 6 Human immuno deficiency virus HIV HIV HV 25 4 IL28B SNPs IL28B ype IFN IFNIFN 3 26,27 IFN IFN IFN IFN IPA 28 IP RBV AP HV

6 212 Peg IFN RBV Peg IFN HV 29,30 SNPs WAS 1 ohen J he scientific challenge of hepatitis. Science , Rumi M, et al Randomized study of peginterferon alpha2a plus ribavirin vs peginterferon alpha2b plus ribavirin in chronic hepatitis. astroenterology , Manns MP, et al Peginterferon alfa 2b plus ribavirin compared with interferon alfa 2b plus ribavirin for initial treatment of chronic hepatitis a randomised trial. Lancet , Fried MW, et al Peginterferon alfa 2a plus ribavirin for chronic hepatitis virus infection. N Engl J Med , Buti M, et al Extending combination therapy with peginterferon alfa 2b plus ribavirin for genotype 1 chronic hepatitis late responders a report of 9 cases. Hepatology , Berg, et al Extended treatment duration for hepatitis virus type 1 comparing 48 versus 72 weeks of peginterferon alfa 2a plus ribavirin. astroenterology , Enomoto N, et al Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis virus 1b infection. N Engl J Med , El Shamy A, et al Sequence variation in hepatitis virus nonstructural protein 5A predicts clinical outcome of pegylated interferon ribavirin combination therapy. Hepatology , Akuta A, et al Association of amino acid substitution pattern in core protein of hepatitis virus genotype 1b high viral load and non virological response to interferon ribavirin combination therapy. Intervirology , Lander ES, et al Initial sequencing and analysis of the human genome. Nature , Venter J, et al he sequence of the human genome. Science , Finishing the euchromatic sequence of the human genome. Nature , he International HapMap Project. Nature , Kornum BR, et al ommon variants in P2RY11 are associated with narcolepsy. Nat enet , Nishida N, et al Further development of multiplex single nucleotide polymorphism typing method, the Digiag2 assay. Anal Biochem , Yasuda K, et al Variants in KNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat enet , anaka Y, et al enome wide association of IL28B with response to pegylated interferon alpha and ribavirin therapy for chronic hepatitis. Nat enet , Suppiah V, et al IL28B is associated with response to chronic hepatitis interferon alpha and ribavirin therapy. Nat enet , e D, et al enetic variation in IL28B predicts hepatitis treatment induced viral clearance. Nature , Fellay J, et al IPA gene variants protect against anaemia in patients treated for chronic hepatitis. Nature , Sakamoto N, et al IPA gene variant protects against anemia induced by pegylated interferon alpha and ribavirin therapy for Japanese patients with chronic hepatitis. Hepatol Res , Ochi H, et al IPA polymorphism affects

7 Vol. 24 No ribavirin induced anemia and outcomes of therapy a genome wide study of Japanese HV virus patients. astroenterology , homas DL, et al enetic variation in IL28B and spontaneous clearance of hepatitis virus. Nature , Kurbanov F, et al enetic polymorphism in IL28B is associated with spontaneous clearance of hepatitis virus genotype 4 infection in an Egyptian cohort. J Infect Dis , Rauch A, et al enetic variation in IL28B is associated with chronic hepatitis and treatment failure a genome wide association study. astroenterology , Sheppard P, et al IL 28, IL 29 and their class cytokine receptor IL 28R. Nat Immunol , Kotenko SV, et al IFN lambdas mediate antiviral protection through a distinct class cytokine receptor complex. Nat Immunol , Hitomi Y, et al Inosine triphosphate protects against ribavirin induced adenosine triphosphate loss by adenylosuccinate synthase function. astroenterology , hung R A watershed momnt I the treatment of hepatitis. N Engl J Med , 30 Dieterich D he end of the beginning for hepatitis treatment. Hepatology ,