scholarly journals Closing in on the Target: Sustained Virologic Response in Hepatitis C Virus Genotype 1 Infection Response-Guided Therapy

2013 ◽  
Vol 56 (10) ◽  
pp. 1466-1470 ◽  
Author(s):  
E. Lontok ◽  
N. Mani ◽  
P. R. Harrington ◽  
V. Miller
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Infection Response ◽  
Guided Therapy

scholarly journals Clinical Implications of Detectable Baseline Hepatitis C Virus-Genotype 1 NS3/4A-Protease Variants on the Efficacy of Boceprevir Combined With Peginterferon/Ribavirin

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
John A. Howe ◽  
Jianmin Long ◽  
Stuart Black ◽  
Robert Chase ◽  
Patricia McMonagle ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Failure ◽  
Virologic Response ◽  
Phase Iii ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Virus Genotype ◽  
The Impact

Abstract Background.  We analyzed the impact of pretreatment variants conferring boceprevir-resistance on sustained virologic response (SVR) rates achieved with boceprevir plus peginterferon-α/ribavirin (P/R) for hepatitis C virus (HCV)-genotype-1 infection. Methods.  NS3-protease-polymorphisms emerging coincident with virologic failure on boceprevir/P/R regimens were identified as resistance-associated variants (RAVs). Baseline samples pooled from 6 phase II or phase III clinical trials were analyzed for RAVs by population sequencing. Interferon (IFN)-responsiveness was predefined as >1 log reduction in HCV-RNA level during the initial 4-week lead-in treatment with P/R before boceprevir was added. The effective boceprevir-concentration inhibiting RAV growth by 50% (EC50) was determined using a replicon assay relative to the wild-type referent. Results.  Sequencing was performed in 2241 of 2353 patients (95.2%) treated with boceprevir. At baseline, RAVs were detected in 178 patients (7.9%), including 153 of 1498 genotype-1a infections (10.2%) and 25 of 742 genotype-1b infections (3.4%) (relative risk, 3.03; 95% confidence interval [CI], [2.01, 4.58]). For IFN-responders, SVR24 (SVR assessed 24 weeks after discontinuation of all study medications) rates were 78% and 76% with or without RAVs detected at baseline, respectively. For the 510 poor IFN-responders, SVR24 rates were 8 of 36 subjects (22.2% [11.7%, 38.1%]) when baseline RAVs were detected vs 174 of 474 subjects (36.7% [32.5%, 41.1%]) when baseline RAVs were not detected (relative likelihood of SVR24 [95% CI], 0.61 [0.32, 1.05]). Sustained virologic response was achieved in 7 of 8 (87.5%) IFN-nonresponders with baseline variants exhibiting ≤2-fold increased EC50 for boceprevir in a replicon assay, whereas only 1 of 15 (7%) IFN-nonresponders with baseline RAVs associated with ≥3-fold increased EC50 achieved SVR. Conclusions.  Baseline protease-variants appear to negatively impact SVR rates for boceprevir/P/R regimens only when associated with decreased boceprevir susceptibility in vitro after a poor IFN-response during the lead-in period.

scholarly journals IL28B SNP rs12979860 Is a Critical Predictor for On-Treatment and Sustained Virologic Response in Patients with Hepatitis C Virus Genotype-1 Infection

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18322 ◽  
Author(s):  
Chun-Yen Lin ◽  
Ji-Yih Chen ◽  
Tsung-Nan Lin ◽  
Wen-Juei Jeng ◽  
Chien-Hao Huang ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Genotype 1 ◽  
Virus Genotype

What is expected from the novel triple combination antiviral treatment of patients infected with hepatitis C virus genotype 1?

2013 ◽  
Vol 154 (7) ◽  
pp. 257-261
Author(s):  
Anna Tusnádi ◽  
Anna Szabó
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Antiviral Treatment ◽  
Dual Therapy ◽  
Virologic Response ◽  
Triple Combination ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Response Method

Introduction: Since May 2011, protease inhibitor/ribavirin/peginterferon combination has become the standard treatment for both treatment-naive and treatment-experienced patients infected with hepatitis C virus genotype 1. In Hungary, due to limited resources, the therapy of treatment-experienced patients might only be financed in the near future. Aim: The aim of this retrospective study was to find out characteristics of the patient group waiting for new triple combination in a single hepatology centre in Hungary, and to estimate the possible rate of their sustained virologic response. Method: Between January 2004 and September 2012, 269 patients with chronic hepatitis C virus infection were treated with peginterferon/ribavirin therapy. 142 patients failed to achieve sustained virologic response, but out of them, 93 individuals are the possible candidates for the triple antiviral treatment. In the latter group, the previous virologic response to dual therapy was determined. To register fibrosis scores, findings of liver biopsy and/or fibroelastography were also collected. Interleukin28B genotypes of 49 patients were determined. Results: Among the 93 treatment-experienced patients, 25 relapsed, 26 responded partially , 6 broke through, and 36 null-responders were found. 29% of patients had mild or moderate fibrosis and 71% of those already had severe fibrosis. Of the 49 patients with known interleukin28B genotype only 8 patients had the CC genotype. Conclusions: About half of the patients (mostly relapsers, and some partial responders as well) have a good chance of achieving sustained virologic response, which may be influenced by the fibrosis score. Orv. Hetil., 2013, 154, 257–261.

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