Impact of <scp><i>IL28B</i></scp> polymorphisms on 24‐week telaprevir‐based combination therapy for <scp>A</scp>sian chronic hepatitis <scp>C</scp> patients with hepatitis <scp>C</scp> virus genotype 1b

Tsubota, Akihito; Shimada, Noritomo; Atsukawa, Masanori; Abe, Hiroshi; Kato, Kazúo; Ika, Makiko; Miyata, Hiroshi; Nagatsuma, Keisuke; Matsuura, Tomokazu; Aizawa, Yoshifusa

doi:10.1111/jgh.12402

Cited by 21 publications

(29 citation statements)

References 27 publications

(124 reference statements)

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“…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. 107,109,115 Because the numbers of Asian HCV-1 patients who received BOC were low, and no studies were designed for TVR-based RGT in Asian HCV-1 patients, the optimized strategies for shortening treatment duration on the basis of early viral kinetics and IL-28B genotypes have not yet been determined.…”

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

confidence: 68%

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

confidence: 68%

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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“…Predictors of treatment outcome by telaprevir‐based triple therapy have been reported in real‐world clinical practice in Japan . These reports found that prior treatment response to PEG‐IFN α /ribavirin, IL‐28B genotype and liver fibrosis had an effect on the success of treatment.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure

Ogawa

Furusyo

Dohmen

et al. 2015

Journal of Viral Hepatitis

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Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.

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“…Addition of telaprevir to the PEG IFN‐α/RBV combination remarkably improves the SVR rate in both treatment‐naïve and previously treated patients, which may decrease the value of IL28B SNP as a predictor of SVR . However, in the 24‐week telaprevir‐based triple therapy for HCV G1b Japanese patients, IL28B SNP still remained informative as a strong predictor of SVR: the rate of 94–97% for those with the rs8099917 major genotype TT and 50–56% for those with the minor genotype TG/GG . Therefore, this study focused on patients with the unfavorable IL28B minor genotype and analyzed factors associated with SVR in such a refractory patient subgroup.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, single nucleotide polymorphisms (SNP) near the interleukin‐28B ( IL28B ) gene was one of the most important predictors of SVR in PEG IFN‐α/RBV dual combination therapy . Although it was reported that the value of the IL28B SNP is attenuated with 48‐week PEG IFN‐α/RBV/telaprevir triple therapy in a predominantly Caucasian cohort, the SNP remained informative as a predictor of SVR to 24‐week PEG IFN‐α/RBV/telaprevir triple therapy for East Asian genotype 1b (G1b) patients . In a previous East Asian cohort treated with the 24‐week telaprevir‐based triple therapy, the SVR rate was very high (94–97%) in patients with the rs8099917 genotype TT ( IL28B major genotype), whereas it was relatively low (50–56%) in those with the genotype TG/GG ( IL28B minor genotype) .…”

Section: Introductionmentioning

confidence: 99%

“…Although it was reported that the value of the IL28B SNP is attenuated with 48‐week PEG IFN‐α/RBV/telaprevir triple therapy in a predominantly Caucasian cohort, the SNP remained informative as a predictor of SVR to 24‐week PEG IFN‐α/RBV/telaprevir triple therapy for East Asian genotype 1b (G1b) patients . In a previous East Asian cohort treated with the 24‐week telaprevir‐based triple therapy, the SVR rate was very high (94–97%) in patients with the rs8099917 genotype TT ( IL28B major genotype), whereas it was relatively low (50–56%) in those with the genotype TG/GG ( IL28B minor genotype) . Therefore, patients with the IL28B minor genotype remain difficult to treat and further information is required to determine what patients should be treated or wait for the next‐generation treatment.…”

Section: Introductionmentioning

confidence: 99%

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Factors associated with sustained virological response in 24‐week telaprevir‐based triple therapy for chronic hepatitis C genotype 1b patients with the IL28B minor genotype

Abe

Tsubota

Shimada

et al. 2014

Hepatology Research

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Impact of IL28B polymorphisms on 24‐week telaprevir‐based combination therapy for Asian chronic hepatitis C patients with hepatitis C virus genotype 1b

Abstract: The IL28B single nucleotide polymorphism still remained informative as a predictor of SVR to 24-week telaprevir-based triple combination therapy for East Asian patients infected with hepatitis C virus genotype 1b.

Cited by 21 publications

References 27 publications

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

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

Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure

Factors associated with sustained virological response in 24‐week telaprevir‐based triple therapy for chronic hepatitis C genotype 1b patients with the IL28B minor genotype

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