scholarly journals Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

2015 ◽  
Vol 53 (7) ◽  
pp. 2195-2202 ◽  
Author(s):  
Sylvie Larrat ◽  
Sophie Vallet ◽  
Sandra David-Tchouda ◽  
Alban Caporossi ◽  
Jennifer Margier ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Triple Therapy ◽  
Pegylated Interferon ◽  
Poor Responders ◽  
Obvious Effect ◽  
Treatment Naïve ◽  
Detection Of Mutations ◽  
The Impact

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a >3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P= 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.

scholarly journals Hepatitis C Virus Clearance after Discontinuation of Pegylated Interferon Alpha-2a Monotherapy in a Child

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Takeshi Endo ◽  
Koichi Ito ◽  
Tokio Sugiura ◽  
Kenji Goto
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Antiviral Treatment ◽  
Pegylated Interferon ◽  
Hcv Rna ◽  
Pegylated Interferon Alpha ◽  
Present Patient

The present patient was a 4-year-old boy. His hepatitis C virus genotype was 2a, and his viral load was high (1400,000 U/mL). The pretreatment liver biopsy revealed no fibrosis or malignancy and mild chronic hepatitis; his Knodell's histological activity (HAI) score was 4. Single nucleotide polymorphism of IL28B (rs8099917) was major type. The patient began antiviral treatment with pegylated interferon alpha 2a (90 μg/week). At week 9, serum HCV RNA became undetectable, with a sensitivity of 50 copies/mL. Antiviral treatment was discontinued at week 11 because the ALT level increased to 610 U/L. After discontinuation of therapy, the patient’s serum HCV RNA status became positive again. The serum viral load increased to 100,000 U/mL. During this period, he had been observed without medication. Sixteen months after stopping treatment, serum HCV became undetectable. Over a 4-year period, HCV RNA became negative and his anti-HCV antibody titer gradually decreased. In conclusion, though antiviral therapy resulted in failure or incomplete therapy, a reduced viral load resulted in viral clearance in the present patient. Interleukin 28B genotype might have association with the clearance of hepatitis C virus after discontinuation of antiviral therapy.

scholarly journals Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients

2014 ◽  
Vol 58 (9) ◽  
pp. 5332-5341 ◽  
Author(s):  
Cédric Laouénan ◽  
Patrick Marcellin ◽  
Martine Lapalus ◽  
Feryel Khelifa-Mouri ◽  
Nathalie Boyer ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Triple Therapy ◽  
Pegylated Interferon ◽  
Hcv Rna ◽  
Second Phase ◽  
Compensated Cirrhosis ◽  
Viral Kinetic ◽  
Significant Difference ◽  
Infected Cells

ABSTRACTTriple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P= 0.5), but there was a significant difference in the 50% effective concentrations (EC50) (P= 0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively,P= 0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day−1) and was higher in patients who subsequently eradicated HCV (P= 0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients.

scholarly journals Differential Impact of Adherence to Pegylated Interferon and Ribavirin in the Treatment of Genotype 1 High Viral Titer Chronic Hepatitis C

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Makoto Numata ◽  
Tatehiro Kagawa ◽  
Sei-ichiro Kojima ◽  
Shunji Hirose ◽  
Naruhiko Nagata ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Previous Treatment ◽  
Pegylated Interferon ◽  
Viral Titer ◽  
Genotype 1 ◽  
Referral Hospitals ◽  
Treatment Naïve ◽  
The Impact

To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%–80%, and <60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%–80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.

scholarly journals Different PEGylated Interferon Ribavirin Therapy in Non-Responders with Chronic Hepatitis C Virus Infection

2012 ◽  
Vol 2 (2) ◽  
pp. 9-13
Author(s):  
Hisham O. Akbar
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Chain Reaction ◽  
Chronic Hepatitis C Virus ◽  
Polymerase Chain

Background: PEGylated interferon and ribavirin therapy is the current standard of care for patients with chronic Hepatitis C virus. It is unknown whether retreatment may be beneficial in non-responders. Methods: Patients who failed to respond to either PEG-Intron or Pegasys with ribavirin were switched to a different PEGylated interferon with ribavirin. Patients were assessed for virologic response by a decrease in viral load levels using a polymerase chain reaction assay. Only patients who had a negative viral load at week 24 were allowed to continue treatment for 48 weeks. Patients with a negative polymerase chain reaction assay after 6 months off treatment were considered as responders to the retreatment regimen. Results: A total of 16 patients were retreated. The combination of Pegasys and ribavirin was administered to 3 patients, and 13 patients received PEG-Intron with ribavirin. Patients had either genotype 1 or 4. Only 4 patients responded to retreatment with PEG-Intron (25%). The responders were female, had a low viral load and had an early significant viral load reduction. Three patients had genotype 4, and one had genotype 1. Conclusion: Retreatment with different PEGylated interferon in patients who failed previous treatment may have a role in the selected patients infected with chronic Hepatitis C virus.

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