Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin

Akuta, Norio; Suzuki, Fumitaka; Hirakawa, Miharu; Kawamura, Yusuke; Yatsuji, Hiromi; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Chayama, Kazuaki; Nakamura, Yusuke; Kumada, Hiromitsu

doi:10.1002/hep.23690

Cited by 238 publications

(231 citation statements)

References 38 publications

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“…In this study, the genotype frequencies observed of individuals of different ethnicities uninfected with HCV are consistent with those of previous studies 14,15 specifically investigating the IL28B SNPs and SVR in HCV-infected patients.…”

Section: Discussionsupporting

confidence: 91%

Simultaneous Genotyping of rs12979860 and rs8099917 Variants Near the IL28B Locus Associated with HCV Clearance and Treatment Response

Melis

Fauron

McMillin

et al. 2011

The Journal of Molecular Diagnostics

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Recent genome-wide association studies have identified two host single-nucleotide polymorphisms (SNPs) near the IL28B gene (rs12979860 C/T and rs8099917 T/G) that are associated with sustained virological response in patients infected with the hepatitis C virus. Herein, we describe a rapid multiplexed dual-color fluorescence resonance energy transfer (FRET) probe assay that accurately genotypes for both SNPs simultaneously. A single-nucleotide extension assay was also developed for verification of genotypes. Agreement (100%) was observed in genotype calls between the FRET and single-nucleotide extension methods for both SNPs, yielding 100% analytical sensitivity and specificity. By using the FRET assay, 443 samples of varying ethnic backgrounds were genotyped and six different compound genotypes (rs12979860/rs8099917) were detected in whites, Asians, Middle Easterners, Hispanics, and African Americans, at the following frequencies: CC/TT (39.2%, 78.9%, 40.0%, 33.9%, and 16.8%), CT/TT (20.8%, 0%, 40%, 9.3%, and 37.0%), TT/TT (2.4%, 0%, 0%, 3.4%, and 35.3%), CT/TG (24.0%, 19.7%, 20%, 39.8%, and 3.4%), TT/TG (8.0%, 1.4%, 0%, 3.4%, and 5.9%), and TT/GG (5.6%, 0%, 0%, 10.2%, and 1.7%), respectively. The multiplexed FRET assay can be used to effectively genotype for both SNPs in a single tube, with high analytical sensitivity and specificity. The global prevalence of hepatitis C virus (HCV) infection is approximately 3%.1 Only approximately 15% of those who contract HCV spontaneously clear the virus. The 85% of patients who become chronically infected are at risk for developing cirrhosis and hepatocellular carcinoma several decades after infection. HCV infection is the most common reason for liver transplantation in the United States.2 Standard-of-care treatment for fine hepatitis C consists of pegylated interferon and ribavirin; however, this treatment is expensive and successful in only 40% to 50% of individuals infected with HCV genotype 1. 3 In addition, the treatment itself is difficult to tolerate. Individuals receiving therapy can experience serious adverse effects, ranging from psychological depression to bone marrow suppression, often resulting in premature withdrawal from treatment. 4 Given the high cost of treatment, the poor response rate for HCV 1, and severe adverse effects, identifying factors that predict response to therapy would be valuable.Recently, multiple independent research groups 5-9 have performed genome-wide association studies and reported several single-nucleotide polymorphisms (SNPs) associated with spontaneous HCV clearance and response to treatment. These SNPs are located in the region of IL28B, IL28A, and IL29 interleukin genes on chromosome 19q13 and represent a recently discovered family of interferons known as type III or interferons. Interferons have inhibited HCV in vitro and are believed to trigger an antiviral cascade through the JAK-STAT pathway. 10,11Two biallelic SNPs rs12979860 (C/T) and rs8099917 (T/G), located upstream of IL28B, have a strong association with both spontane...

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Section: Discussionsupporting

confidence: 91%

Simultaneous Genotyping of rs12979860 and rs8099917 Variants Near the IL28B Locus Associated with HCV Clearance and Treatment Response

Melis

Fauron

McMillin

et al. 2011

The Journal of Molecular Diagnostics

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“…The significance of core 70 substitution has since been confirmed in large-scale studies [47,48]. No substitution at core 70 (70R) was found to be an independent predictive factor for SVR in a large-scale Japanese study into HCV G1b, treated by PEG-IFN plus RBV [49].…”

Section: Substitutions In Regions Other Than Ns5a In Association Withmentioning

confidence: 95%

“…According to the study of Akuta et al [51] genetic variations near the IL28B gene and aa substitutions in the core region were identified as predictors of viral dynamics during triple therapy.…”

Section: Substitutions In Regions Other Than Ns5a In Association Withmentioning

confidence: 99%

Viral Factors Associated with Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection

Aizawa¹

2014

J Antivir Antiretrovir

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A first-generation protease inhibitor (PI) against HCV non-structural 3/4A serine protease was approved worldwide at the end of 2011. We are now facing a revolutionary change in therapeutic strategies for chronic HCV infection, from interferon (IFN)-based therapies to direct-acting antivirals (DAAs). The efficacy of antiviral therapy varies with HCV genotype. The most intractable and most common HCV worldwide is HCV genotype 1 (G1). Viral and host factors participating in the virological outcome of IFN-based therapy have been extensively examined. However, in the era of DAAs, the significance of these factors will gradually decrease. Instead, viral factors related to resistance against DAAs are becoming the main focus. In this review, the viral factors participating in the response to IFN-based therapies are summarized, and the issue of viral resistance to DAAs is discussed.

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“…Data from these studies showed that the SVR rates of TVR-based triple therapy for 12 weeks were only 45% in treatment-naïve patients. 107,108 The SVR rates increased to 70%-82% with an additional 12 weeks of PEG-IFN α plus RBV, except for one small trial 112 enrolling the most difficult-to-treat partial responders and nonresponders, which showed an SVR rate of 27%. 107,[109][110][111][112][113][114][115] In line with Western reports, IL-28B genotypes and RVR strongly affected the SVR rates in Asian HCV-1 patients receiving BOC-or TVR-based triple therapy.…”

Section: Boc or Tvr-based Triple Therapy In Asian Patients With Chronmentioning

confidence: 99%

Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

Liu¹,

Kao

2014

IJN

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Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility.

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Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin

Cited by 238 publications

References 38 publications

Simultaneous Genotyping of rs12979860 and rs8099917 Variants Near the IL28B Locus Associated with HCV Clearance and Treatment Response

Simultaneous Genotyping of rs12979860 and rs8099917 Variants Near the IL28B Locus Associated with HCV Clearance and Treatment Response

Viral Factors Associated with Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection

Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

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