New Hepatitis C Therapies: The Toolbox, Strategies, and Challenges

Pawlotsky, Jean‐Michel

doi:10.1053/j.gastro.2014.03.003

Cited by 474 publications

(403 citation statements)

References 70 publications

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“…[2][3][4] While this approach is very useful for the treatment of HCV infection, it is extremely expensive at present. 5) Therefore, the well-established approach of combining pegylated interferon (PEG-IFN) and ribavirin to treat chronic HCV infection is still used in particular situations.…”

mentioning

confidence: 99%

Comparison of the Safety Profiles of Pegylated Interferon α-2a and α-2b Administered in Combination with Ribavirin for Chronic Hepatitis C Infection: A Real-World Retrospective Cohort Study

Ide

Sato

Imai

et al. 2016

Biological & Pharmaceutical Bulletin

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This study compares the safety profiles of pegylated interferon (PEG-IFN) α-2a and α-2b administered in combination with ribavirin, based on the variable of time to withdrawal from treatment due to adverse events. We conducted a real-world retrospective cohort study using the Japanese interferon database. Based on eligibility criteria, individuals with chronic hepatitis C virus (HCV) infection were identified in the database covering the period December 2009 to August 2015. The primary outcome measure was defined as difference in time to withdrawal from treatment due to adverse events between patients receiving PEG-IFN α-2a combined with ribavirin and those receiving PEG-IFN α-2b combined with ribavirin. The difference was analyzed using the multivariate Cox proportional hazards regression model. A frailty model was also applied to consider regional (prefectural) variation. After eligibility evaluation, 11058 individuals were included in the analysis. 3774 were treated with PEG-IFN α-2a, and 6764 with PEG-IFN α-2b, with 11.84 and 12.30% respectively withdrawing from treatment due to adverse events. The Cox model showed no significant difference between the two groups (hazard ratio (HR), 95%CI; 0.918, 0.817 to 1.031; p 0.1475). The results were consistent even when regional variation and other confounding variables were adjusted in the frailty model. In conclusion, there may be no difference in time to withdrawal from treatment due to adverse events between PEG-IFN α-2a and PEG-IFN α-2b combined with ribavirin. Applying the method used here to future studies using novel treatment regimens may also provide important information for the treatment of chronic HCV infection in clinical practice.

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mentioning

confidence: 99%

Comparison of the Safety Profiles of Pegylated Interferon α-2a and α-2b Administered in Combination with Ribavirin for Chronic Hepatitis C Infection: A Real-World Retrospective Cohort Study

Ide

Sato

Imai

et al. 2016

Biological & Pharmaceutical Bulletin

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“…irect-acting antiviral agents (DAAs) (1) targeting the nonstructural 3 (NS3)/4A protease, the NS5A protein, or the NS5B RNA-dependent RNA polymerase of hepatitis C virus (HCV) are increasingly used in the treatment of chronic hepatitis C, either as part of triple combination therapies (triple therapy) with pegylated interferon (pegIFN) and ribavirin, or in combination with several other DAAs in an IFN-free regimen (2,3). Due to the high rate of viral turnover and the error-prone activity of the HCV polymerase, HCV replication results in the constant production of numerous variants that are selected to constitute the viral quasispecies.…”

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confidence: 99%

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

et al. 2015

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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 (IC 50 ) 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.

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“…4 There is a lack of data on new interferon-free regimens in patients with decompensated cirrhosis, who could greatly benefit from such regimens and eventually be removed from liver transplant wait lists. 5 This is, to our knowledge, the first report of delisting from the liver transplant wait list for a patient with HCV-induced decompensated cirrhosis. This observation is a proof of concept that all-oral, interferon-free combinations could substantially reduce the need for liver transplantation in patients with HCV-related decompensated cirrhosis if the clinical outcome seen in this case is confirmed to be frequent in controlled clinical trials and real-life cohorts.…”

Section: To the Editorsmentioning

confidence: 76%

Patient with decompensated hepatitis C virus–related cirrhosis delisted for liver transplantation after successful sofosbuvir‐based treatment

Ruiz¹,

Féray

Pawlotsky

et al. 2015

Liver Transpl

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New Hepatitis C Therapies: The Toolbox, Strategies, and Challenges

Cited by 474 publications

References 70 publications

Comparison of the Safety Profiles of Pegylated Interferon α-2a and α-2b Administered in Combination with Ribavirin for Chronic Hepatitis C Infection: A Real-World Retrospective Cohort Study

Comparison of the Safety Profiles of Pegylated Interferon α-2a and α-2b Administered in Combination with Ribavirin for Chronic Hepatitis C Infection: A Real-World Retrospective Cohort Study

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

Patient with decompensated hepatitis C virus–related cirrhosis delisted for liver transplantation after successful sofosbuvir‐based treatment

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