Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C

Takasuke Fukuhara, Akinobu Taketomi, Takashi Motomura, Shinji Okano, Akinori Ninomiya, Takayuki Abe, Hideaki Uchiyama, Yuji Soejima, Ken Shirabe, Yoshiharu Matsuura, Yoshihiko Maehara

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Abstract

Background & Aims: Patients with hepatitis C virus (HCV)-related liver disease frequently undergo orthotopic liver transplantation, but recurrent hepatitis C is still a major cause of morbidity. Patients are treated with peg-interferon and ribavirin (PEG-IFN/RBV), which has substantial side effects and is costly. We investigated genetic factors of host, liver donor, and virus that might predict sensitivity of patients with recurrent hepatitis C to PEG-IFN/RBV. Methods: Liver samples were analyzed from 67 HCV-infected recipients and 41 liver donors. Liver recipient and donor DNA samples were screened for single nucleotide polymorphisms near the IL28B genes (rs12980275 and rs8099917) that affect sensitivity to PEG-IFN/RBV. HCV RNA was isolated from patients and analyzed for mutations in the core, the IFN sensitivity- determining region, and IFN/RBV resistance-determining regions in nonstructural protein 5A. Results: In liver recipients and donors, the IL28B single nucleotide polymorphism rs8099917 was significantly associated with a sustained viral response (SVR; P = 0.003 and P = .025, respectively). Intrahepatic expression of IL28 messenger RNA was significantly lower in recipients and donors that carried the minor alleles (T/G or T/T) in rs8099917 (P = .010 and .009, respectively). Genetic analyses of IL28B in patients and donors and of the core and nonstructural protein 5A regions encoded by HCV RNA predicted an SVR with 83% sensitivity and 82% specificity; this was more effective than analysis of any single genetic feature. Conclusions: In patients with recurrent HCV infection after orthotopic liver transplantation, combination analyses of single nucleotide polymorphisms of IL28B in recipient and donor tissues and mutations in HCV RNA allow prediction of SVR to PEG-IFN/RBV therapy.

Original languageEnglish
Pages (from-to)1577-1585.e3
JournalGastroenterology
Volume139
Issue number5
DOIs
Publication statusPublished - Nov 2010

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Ribavirin
Hepatitis C
Interferons
Hepacivirus
Tissue Donors
Liver
Single Nucleotide Polymorphism
RNA
Liver Transplantation
Therapeutics
Mutation
Virus Diseases
Liver Diseases
Proteins
Alleles
Viruses
Morbidity
Sensitivity and Specificity
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C. / Fukuhara, Takasuke; Taketomi, Akinobu; Motomura, Takashi; Okano, Shinji; Ninomiya, Akinori; Abe, Takayuki; Uchiyama, Hideaki; Soejima, Yuji; Shirabe, Ken; Matsuura, Yoshiharu; Maehara, Yoshihiko.

In: Gastroenterology, Vol. 139, No. 5, 11.2010, p. 1577-1585.e3.

Research output: Contribution to journalArticle

Fukuhara, T, Taketomi, A, Motomura, T, Okano, S, Ninomiya, A, Abe, T, Uchiyama, H, Soejima, Y, Shirabe, K, Matsuura, Y & Maehara, Y 2010, 'Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C', Gastroenterology, vol. 139, no. 5, pp. 1577-1585.e3. https://doi.org/10.1053/j.gastro.2010.07.058
Fukuhara, Takasuke ; Taketomi, Akinobu ; Motomura, Takashi ; Okano, Shinji ; Ninomiya, Akinori ; Abe, Takayuki ; Uchiyama, Hideaki ; Soejima, Yuji ; Shirabe, Ken ; Matsuura, Yoshiharu ; Maehara, Yoshihiko. / Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C. In: Gastroenterology. 2010 ; Vol. 139, No. 5. pp. 1577-1585.e3.
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abstract = "Background & Aims: Patients with hepatitis C virus (HCV)-related liver disease frequently undergo orthotopic liver transplantation, but recurrent hepatitis C is still a major cause of morbidity. Patients are treated with peg-interferon and ribavirin (PEG-IFN/RBV), which has substantial side effects and is costly. We investigated genetic factors of host, liver donor, and virus that might predict sensitivity of patients with recurrent hepatitis C to PEG-IFN/RBV. Methods: Liver samples were analyzed from 67 HCV-infected recipients and 41 liver donors. Liver recipient and donor DNA samples were screened for single nucleotide polymorphisms near the IL28B genes (rs12980275 and rs8099917) that affect sensitivity to PEG-IFN/RBV. HCV RNA was isolated from patients and analyzed for mutations in the core, the IFN sensitivity- determining region, and IFN/RBV resistance-determining regions in nonstructural protein 5A. Results: In liver recipients and donors, the IL28B single nucleotide polymorphism rs8099917 was significantly associated with a sustained viral response (SVR; P = 0.003 and P = .025, respectively). Intrahepatic expression of IL28 messenger RNA was significantly lower in recipients and donors that carried the minor alleles (T/G or T/T) in rs8099917 (P = .010 and .009, respectively). Genetic analyses of IL28B in patients and donors and of the core and nonstructural protein 5A regions encoded by HCV RNA predicted an SVR with 83{\%} sensitivity and 82{\%} specificity; this was more effective than analysis of any single genetic feature. Conclusions: In patients with recurrent HCV infection after orthotopic liver transplantation, combination analyses of single nucleotide polymorphisms of IL28B in recipient and donor tissues and mutations in HCV RNA allow prediction of SVR to PEG-IFN/RBV therapy.",
author = "Takasuke Fukuhara and Akinobu Taketomi and Takashi Motomura and Shinji Okano and Akinori Ninomiya and Takayuki Abe and Hideaki Uchiyama and Yuji Soejima and Ken Shirabe and Yoshiharu Matsuura and Yoshihiko Maehara",
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T1 - Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C

AU - Fukuhara, Takasuke

AU - Taketomi, Akinobu

AU - Motomura, Takashi

AU - Okano, Shinji

AU - Ninomiya, Akinori

AU - Abe, Takayuki

AU - Uchiyama, Hideaki

AU - Soejima, Yuji

AU - Shirabe, Ken

AU - Matsuura, Yoshiharu

AU - Maehara, Yoshihiko

PY - 2010/11

Y1 - 2010/11

N2 - Background & Aims: Patients with hepatitis C virus (HCV)-related liver disease frequently undergo orthotopic liver transplantation, but recurrent hepatitis C is still a major cause of morbidity. Patients are treated with peg-interferon and ribavirin (PEG-IFN/RBV), which has substantial side effects and is costly. We investigated genetic factors of host, liver donor, and virus that might predict sensitivity of patients with recurrent hepatitis C to PEG-IFN/RBV. Methods: Liver samples were analyzed from 67 HCV-infected recipients and 41 liver donors. Liver recipient and donor DNA samples were screened for single nucleotide polymorphisms near the IL28B genes (rs12980275 and rs8099917) that affect sensitivity to PEG-IFN/RBV. HCV RNA was isolated from patients and analyzed for mutations in the core, the IFN sensitivity- determining region, and IFN/RBV resistance-determining regions in nonstructural protein 5A. Results: In liver recipients and donors, the IL28B single nucleotide polymorphism rs8099917 was significantly associated with a sustained viral response (SVR; P = 0.003 and P = .025, respectively). Intrahepatic expression of IL28 messenger RNA was significantly lower in recipients and donors that carried the minor alleles (T/G or T/T) in rs8099917 (P = .010 and .009, respectively). Genetic analyses of IL28B in patients and donors and of the core and nonstructural protein 5A regions encoded by HCV RNA predicted an SVR with 83% sensitivity and 82% specificity; this was more effective than analysis of any single genetic feature. Conclusions: In patients with recurrent HCV infection after orthotopic liver transplantation, combination analyses of single nucleotide polymorphisms of IL28B in recipient and donor tissues and mutations in HCV RNA allow prediction of SVR to PEG-IFN/RBV therapy.

AB - Background & Aims: Patients with hepatitis C virus (HCV)-related liver disease frequently undergo orthotopic liver transplantation, but recurrent hepatitis C is still a major cause of morbidity. Patients are treated with peg-interferon and ribavirin (PEG-IFN/RBV), which has substantial side effects and is costly. We investigated genetic factors of host, liver donor, and virus that might predict sensitivity of patients with recurrent hepatitis C to PEG-IFN/RBV. Methods: Liver samples were analyzed from 67 HCV-infected recipients and 41 liver donors. Liver recipient and donor DNA samples were screened for single nucleotide polymorphisms near the IL28B genes (rs12980275 and rs8099917) that affect sensitivity to PEG-IFN/RBV. HCV RNA was isolated from patients and analyzed for mutations in the core, the IFN sensitivity- determining region, and IFN/RBV resistance-determining regions in nonstructural protein 5A. Results: In liver recipients and donors, the IL28B single nucleotide polymorphism rs8099917 was significantly associated with a sustained viral response (SVR; P = 0.003 and P = .025, respectively). Intrahepatic expression of IL28 messenger RNA was significantly lower in recipients and donors that carried the minor alleles (T/G or T/T) in rs8099917 (P = .010 and .009, respectively). Genetic analyses of IL28B in patients and donors and of the core and nonstructural protein 5A regions encoded by HCV RNA predicted an SVR with 83% sensitivity and 82% specificity; this was more effective than analysis of any single genetic feature. Conclusions: In patients with recurrent HCV infection after orthotopic liver transplantation, combination analyses of single nucleotide polymorphisms of IL28B in recipient and donor tissues and mutations in HCV RNA allow prediction of SVR to PEG-IFN/RBV therapy.

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