Accepted Article
Revised, Nagaoki Y, et al., HEPRES-13-0978-R1, page 1
IFNL4 polymorphism affects on outcome of telaprevir, peg-interferon and ribavirin combination therapy for chronic hepatitis C1
Yuko Nagaoki1, Michio Imamura1, Yoshiiku Kawakami1, Hiromi Kan1, Hatsue Fujino1,
5
Takayuki Fukuhara1, Tomoki Kobayashi1, Atsushi Ono1, Takashi Nakahara1, Noriaki Naeshiro1, Ayako Urabe1, Satoe Yokoyama1, Daisuke Miyaki1, Eisuke Murakami1, Tomokazu Kawaoka1, Masataka Tsuge1, Akira Hiramatsu1, Hiroshi Aikata1, Shoichi Takahashi1, C. Nelson Hayes1, Hidenori Ochi2, Kazuaki Chayama1,2, Hiroshima Liver Study
Group
10
1
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of
Biomedical & Health Science, Hiroshima University, Hiroshima, Japan 2
Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical
and Chemical Research (RIKEN), Hiroshima, Japan
15
Running title: IFNL4 polymorphism for TVR/PEG-IFN/RBV
Word count: Abstract, 173 words; Main text, 2,537 words
20
Abbreviations:
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/hepr.12336 This article is protected by copyright. All rights reserved.
Accepted Article
Revised, Nagaoki Y, et al., HEPRES-13-0978-R1, page 2
core70: HCV core protein amino acid 70, HCV: hepatitis C virus, IFNL4:
interferon-lambda 4, PCR: polymerase chain reaction, PEG-IFN: peg-interferon, RBV: ribavirin, RVR: rapid virological response, SNP: single nucleotide polymorphism, SVR:
25
sustained virological response, TVR: telaprevir
Footnotes
This work was supported by Grants-in-Aid for scientific research and development from the Ministry of Health, Labor and Welfare and Ministry of Education Culture
30
Sports Science and Technology, Government of Japan. The funders had no role in
study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Conflict of interest: The authors have declared that no conflicts of interest exist.
35
Corresponding author:
Prof. Kazuaki Chayama, MD, PhD Department of Gastroenterology and Metabolism, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
40
Tel: +81-82-257-5190, Fax: +81-82-255-6220 E-mail: [email protected]
This article is protected by copyright. All rights reserved.
Accepted Article
Revised, Nagaoki Y, et al., HEPRES-13-0978-R1, page 3
Abstract
Aim: The predictive value of the recently identified interferon lamda (IFNL) 4 polymorphism
45
on the outcome of telaprevir (TVR), peg-interferon (PEG-IFN) plus ribavirin (RBV)
combination therapy for chronic hepatitis C is unknown. Methods: We assessed predictive factors for sustained virological response (SVR) for TVR, PEG-IFN plus RBV combination therapy in 283 genotype 1 chronic hepatis C patients. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.
50
Results: SVR rates for patients with IFNL4 TT/TT genotype were significantly higher than
for those with the IFNL4 TT/ΔG or ΔG/ΔG genotypes (93% and 59%, respectively, P
Revised, Nagaoki Y, et al., HEPRES-13-0978-R1, page 1
IFNL4 polymorphism affects on outcome of telaprevir, peg-interferon and ribavirin combination therapy for chronic hepatitis C1
Yuko Nagaoki1, Michio Imamura1, Yoshiiku Kawakami1, Hiromi Kan1, Hatsue Fujino1,
5
Takayuki Fukuhara1, Tomoki Kobayashi1, Atsushi Ono1, Takashi Nakahara1, Noriaki Naeshiro1, Ayako Urabe1, Satoe Yokoyama1, Daisuke Miyaki1, Eisuke Murakami1, Tomokazu Kawaoka1, Masataka Tsuge1, Akira Hiramatsu1, Hiroshi Aikata1, Shoichi Takahashi1, C. Nelson Hayes1, Hidenori Ochi2, Kazuaki Chayama1,2, Hiroshima Liver Study
Group
10
1
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of
Biomedical & Health Science, Hiroshima University, Hiroshima, Japan 2
Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical
and Chemical Research (RIKEN), Hiroshima, Japan
15
Running title: IFNL4 polymorphism for TVR/PEG-IFN/RBV
Word count: Abstract, 173 words; Main text, 2,537 words
20
Abbreviations:
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/hepr.12336 This article is protected by copyright. All rights reserved.
Accepted Article
Revised, Nagaoki Y, et al., HEPRES-13-0978-R1, page 2
core70: HCV core protein amino acid 70, HCV: hepatitis C virus, IFNL4:
interferon-lambda 4, PCR: polymerase chain reaction, PEG-IFN: peg-interferon, RBV: ribavirin, RVR: rapid virological response, SNP: single nucleotide polymorphism, SVR:
25
sustained virological response, TVR: telaprevir
Footnotes
This work was supported by Grants-in-Aid for scientific research and development from the Ministry of Health, Labor and Welfare and Ministry of Education Culture
30
Sports Science and Technology, Government of Japan. The funders had no role in
study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Conflict of interest: The authors have declared that no conflicts of interest exist.
35
Corresponding author:
Prof. Kazuaki Chayama, MD, PhD Department of Gastroenterology and Metabolism, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
40
Tel: +81-82-257-5190, Fax: +81-82-255-6220 E-mail: [email protected]
This article is protected by copyright. All rights reserved.
Accepted Article
Revised, Nagaoki Y, et al., HEPRES-13-0978-R1, page 3
Abstract
Aim: The predictive value of the recently identified interferon lamda (IFNL) 4 polymorphism
45
on the outcome of telaprevir (TVR), peg-interferon (PEG-IFN) plus ribavirin (RBV)
combination therapy for chronic hepatitis C is unknown. Methods: We assessed predictive factors for sustained virological response (SVR) for TVR, PEG-IFN plus RBV combination therapy in 283 genotype 1 chronic hepatis C patients. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.
50
Results: SVR rates for patients with IFNL4 TT/TT genotype were significantly higher than
for those with the IFNL4 TT/ΔG or ΔG/ΔG genotypes (93% and 59%, respectively, P
