Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients

We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b)...

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Main Authors: Hiroshi Abe, Akihito Tsubota, Noritomo Shimada, Masanori Atsukawa, Keizo Kato, Koichi Takaguchi, Toru Asano, Yoshimichi Chuganji, Choitsu Sakamoto, Hidenori Toyoda, Takashi Kumada, Tatsuya Ide, Michio Sata, Yoshio Aizawa
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2014/549709
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author Hiroshi Abe
Akihito Tsubota
Noritomo Shimada
Masanori Atsukawa
Keizo Kato
Koichi Takaguchi
Toru Asano
Yoshimichi Chuganji
Choitsu Sakamoto
Hidenori Toyoda
Takashi Kumada
Tatsuya Ide
Michio Sata
Yoshio Aizawa
author_facet Hiroshi Abe
Akihito Tsubota
Noritomo Shimada
Masanori Atsukawa
Keizo Kato
Koichi Takaguchi
Toru Asano
Yoshimichi Chuganji
Choitsu Sakamoto
Hidenori Toyoda
Takashi Kumada
Tatsuya Ide
Michio Sata
Yoshio Aizawa
author_sort Hiroshi Abe
collection DOAJ
description We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-α-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10−4). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10−5). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.
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spelling doaj-art-537e87fa9ade47beb71a4ea8a2010fa22025-08-20T02:05:31ZengWileyGastroenterology Research and Practice1687-61211687-630X2014-01-01201410.1155/2014/549709549709Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C PatientsHiroshi Abe0Akihito Tsubota1Noritomo Shimada2Masanori Atsukawa3Keizo Kato4Koichi Takaguchi5Toru Asano6Yoshimichi Chuganji7Choitsu Sakamoto8Hidenori Toyoda9Takashi Kumada10Tatsuya Ide11Michio Sata12Yoshio Aizawa13Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-0062, JapanInstitute of Clinical Medicine and Research, The Jikei University School of Medicine, Kashiwa, Chiba, JapanDepartment of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, JapanDivision of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, JapanDepartment of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, JapanDepartment of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, JapanDepartment of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Tokyo, JapanDepartment of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Tokyo, JapanDepartment of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, JapanDepartment of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, JapanDepartment of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, JapanDivision of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, JapanDivision of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-0062, JapanWe evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-α-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10−4). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10−5). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.http://dx.doi.org/10.1155/2014/549709
spellingShingle Hiroshi Abe
Akihito Tsubota
Noritomo Shimada
Masanori Atsukawa
Keizo Kato
Koichi Takaguchi
Toru Asano
Yoshimichi Chuganji
Choitsu Sakamoto
Hidenori Toyoda
Takashi Kumada
Tatsuya Ide
Michio Sata
Yoshio Aizawa
Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients
Gastroenterology Research and Practice
title Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients
title_full Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients
title_fullStr Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients
title_full_unstemmed Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients
title_short Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients
title_sort predictors of response to 24 week telaprevir based triple therapy for treatment naive genotype 1b chronic hepatitis c patients
url http://dx.doi.org/10.1155/2014/549709
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