C (HCV) HCV (IFN) (RBV) 50% (Fukuhara T, Taketomi A, et al. J Hepatol 2010; Fukuhara T, Taketomi A, et al. Gastroenterology 2010 ) IL28B

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C (HCV) 150 2 HCV (IFN) (RBV) 50% 40%C (Former A, et al. Semin Liver Dis 2010) HCV (Schiano TD, et al. Hepatology 2005) C (Moonka D, et al. Am J Transpl 2009)C IFN+RBV 30% (Poordad F, et al.

2 C (HCV) HCV (IFN) (RBV) 50% 40%C (Former A, et al. Semin Liver Dis 2010) HCV (Schiano TD, et al. Hepatology 2005) C (Moonka D, et al. Am J Transpl 2009)C IFN+RBV 30% (Poordad F, et al. Hepatology 2010) HCV IFN Core NS5A Interferon Sensitivity Determining Region (ISDR: ) Interferon/Rivabirin Resistance Determining Region (IRRDR: )3 (Akuta N, et al. J Med Virol 2007; Enomoto N, et al. N Engl J Med 1996) IL28B (SNP:rs ) IFN (Tanaka Y, et al. Nat Genet 2009 HCV IFN C QOL 40HCV C C IFN C IL28B (SNP) C (1)IL28B HCV IFN 67 Donor Recipient SNP IFN (Fukuhara T, Taketomi A, et al. J Hepatol 2010; Fukuhara T, Taketomi A, et al. Gastroenterology 2010) IL28B IFN C C IL28B genotyping genotyping genomic DNA Applied Biosystems StepOneTM genotyping 1 PCR IL28B

(2)IL28B SNP IFN IL28B SNP IFN IL28B SNP interferon sensitivity gene (ISG) Replicon system HCVcc

3% IFN 60.4%Peg-IFNα2b 28.9%IFN10.7% Peg-IFNα2a C 5 10 SVR 94.1%83.0%SVR 79.7%60.8%p<0.

4%TG/GG(minor)16.0% 172 TT major 131 (76.2%)TG/GG minor 41 (23.8%)SVR major 52.3%minor 21.

3 (2)IL28B SNP IFN IL28B SNP IFN IL28B SNP interferon sensitivity gene (ISG) Replicon system HCVcc IL28B SNP (3)IFN IL28B SNP IFN IFN HCV (1)IL28B HCV IFN 506 C 376 IFN 216 VR 157 SVR VR SVR 64.1%38.3% IFN 60.4%Peg-IFNα2b 28.9%IFN10.7% Peg-IFNα2a C 5 10 SVR 94.1%83.0%SVR 79.7%60.8%p<0.001SVR IL28B 203 TT major allele 147 (72.4%)TG GG minor allele %)TT(major)SVR 56.4%TG/GG(minor)16.0% 172 TT major 131 (76.2%)TG/GG minor 41 (23.8%)SVR major 52.3%minor 21.9% major allele SVR SVR major major (n=110)svr58.2% minor/major, major/minor, minor/minor SVR 15.7%, 16.7%, 28.5% TT major allele SVR

4 60-70% HCVRNA 2 7.2logIU/ml HCVRNA genetic distance Direct acting agent Telaprevir11 RVR 27.3% EVR SVR 90.9% 9 T54A mutaion viral breakthrough mutated virus Telaprevir (2)IL28B SNP IFN IFN-ISG IL28B SNP IFN ISGs IFN+RBV IFN ISG15 PKR OAS mrna ISG IL-28B SNPHCV ISG15mRNA RT-PCR SNP (3)IFN IFN HCV Konishi H, Motomura T, Matsumoto Y, Harimoto N, Ikegami T, Yoshizumi T, Soejima Y, Shirabe K, Fukuhara T, Maehara Y. Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant.j Viral Hepat Jun;21(6): doi: /jvh [Epub ahead of print] 2. Ikegami T, Yoshizumi T, Shirabe K, Maehara Y. Frequent plasma cell hepatitis during telaprevir-based triple therapy for hepatitis C after liver transplantation. J Hepatol Apr;60(4): doi: /j.jhep Akamatsu N, Sugawara Y, Kokudo N, Eguchi S, Fujiwara T, Ohdan H, Nagano H, Taketomi A, Kitagawa Y, Shimada M, Ku Y, Yanaga K, Shirabe K, Ikegami T, Mizokami M, Takeuchi M, Maehara Y. Outcomes of living donor liver transplantation for HCV-positive recipients in Japan: results of a nationwide survey. Transpl Int Mar

5 31. doi: /tri Konishi H, Shirabe K, Yoshiya S, Ikeda T, Ikegami T, Yoshizumi T, Ikawa-Yoshida A, Motomura T, Fukuhara T, Maehara Y. Hepatic interferon-gamma-induced protein-10 expression is more strongly associated with liver fibrosis than interleukin-28b single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C. Hepatol Res Nov;43(11): doi: /hepr Ikegami T, Shirabe K, Yoshizumi T, Furusyo N, Kotoh K, Kato M, Shimoda S, Soejima Y, Motomura T, Fukuhara T, Maehara Y. Impact of conversion from pegylated interferon-α2b to interferon-α2a for treating recurrent hepatitis C after liver transplantation. Transplantation Mar 27;95(6):e doi: /TP.0b013e318283a82e. 6. Morooka Y, Umeshita K, Taketomi A, Shirabe K, Maehara Y, Yamamoto M, Shimamura T, Oshita A, Kanno K, Ohdan H, Kawagishi N, Satomi S, Ogawa K, Hagiwara K, Nagano H. Reliability and validity of a new living liver donor quality of life scale. Surg Today Jul;43(7): Ikegami T, Shirabe K, Yoshizumi T, Aishima S, Taketomi A, Soejima Y, Uchiyama H, Kayashima H, Toshima T, Maehara Y. Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia. Am J Transplant Jul;12(7): Yoshizumi T, Shirabe K, Ikegami T, Kayashima H, Yamashita N, Morita K, Masuda T, Hashimoto N, Taketomi A, Soejima Y, Maehara Y. Impact of Human T-Cell Leukemia Virus Type 1 in Living Donor Liver Transplantation. Am J Transplant Jun;12(6): Soejima Y, Shirabe K, Taketomi A, Yoshizumi T, Uchiyama H, Ikegami T, Ninomiya M, Harada N, Ijichi H, Maehara Y. Left lobe living donor liver transplantation in adults. Am J Transplant Jul;12(7): Yoshizumi T, Shirabe K, Taketomi A, Uchiyama H, Harada N, Ijichi H, Yoshimatsu M, Ikegami T, Soejima Y, Maehara Y. Risk factors that increase mortality after living donor liver transplantation. Transplantation Jan 15;93(1): Motomura T, Koga E, Taketomi A, Fukuhara T, Mano Y, Muto J, Konishi H, Toshima T, Uchiyama H, Yoshizumi T, Shirabe K, Maehara Y. Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype. Hepatol Res Mar;42(3): (1) TAKETOMI AKINOBU (2) MAEHARA YOSHIHIKO SHIRABE KEN MATSUURA YOSHIHARU FUKUHARA TAKASUKE YOSHIZUMI TOMOHARU UCHIYAMA HIDEAKI

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