1360 PEGYLATED INTERFERON-LAMBDA (PEGIFN-λ) SHOWS SUPERIOR VIRAL RESPONSE WITH IMPROVED SAFETY AND TOLERABILITY VERSUS PEGIFNα-2A IN HCV PATIENTS (Gl/2/3/4): EMERGE PHASE IIB THROUGH WEEK 12

Zeuzem, Stefan; Arora, S.; Bacon, B.; Box, Terry; Charlton, Michael; Diago, M.; Dieterich, Doug; Mur, R. Esteban; Everson, G.; Fallon, Michael J.; Ferenci, Péter; Flisiak, Robert; George, Joseph; Ghalib, R.; Gitlin, Norman; Gładysz, Andrzej; Gordon, S.; Greenbloom, Susan; Hassanein, Tarek; Jacobson, Ira M.; Jeffers, L; Kowdley, Kris V.; Lawitz, E.J.; Lee, S.; Leggett, B.; Lueth, Stefan; Nelson, D.; Pockros, P.; Rodrı́guez-Torres, Maribel; Rustgi, V.; Serfaty, Lawrence; Sherman, Michael Y.; Shiffman, M.; Solà, R.; Sulkowski, Mark S.; Vargas, Hugo E.; Vierling, John M.; Yoffe, Boris; Ishak, Laura; Fontana, David; Xu, Deyi; Lester, J.F.; Gray, Todd; Horga, A; Hillson, Jan; Ramos, Eleanor L.; Lopez-Talavera, J.C.; Muir, A.

doi:10.1016/s0168-8278(11)61362-7

Cited by 40 publications

(31 citation statements)

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“…Interestingly, at different weekly doses of PegIFNk (240 to 120 lg), cEVR rates were 55-56.3% compared to 37.9% with 180 lg of PegIFNa in genotype 1 and 4 patients. The tolerability and safety of PegIFNk were better than with PegIFNa, with less anemia and fewer flu-like symptoms [130]. These findings show that PegIFNk has an antiviral effect against HCV.…”

Section: Il-28b and Future Therapiesmentioning

confidence: 65%

Genomics and HCV infection: Progression of fibrosis and treatment response

Estrabaud

Vidaud

Marcellin

et al. 2012

Journal of Hepatology

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HCV infection is a global health problem that affects 170 million people worldwide. The severity of the disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma (HCC). Recently, the standard of care for genotype 1 patients has greatly improved with the addition of protease inhibitors (telaprevir or boceprevir) to pegylated interferon (PegIFN) and ribavirin (RBV). The prediction of fibrosis progression and the response to antiviral treatment are two major issues in the management of patients with chronic hepatitis C. Differential expression of mRNAs was first analyzed for both progression of fibrosis and treatment response. Specific polymorphisms, associated with either fibrosis or viral response, were identified thanks to major improvements in genome scanning technologies. Since 2009, several independent genome wide association studies (GWAS) have reported an association between genetic polymorphisms within the IL-28B promoter and both natural and treatment-induced clearance in genotype 1 infected patients. These different studies showed the strong association and the importance of IL-28B polymorphisms in the treatment response. Combining the different genetic factors could improve their predictive value and help identify patients at a high risk of progression of fibrosis as well as those with a lower chance of responding to treatment. The aim of this review was to discuss the genomic factors (mRNAs, miRNAs, and SNPs) and HCV infection with clinical implications for either progression of fibrosis or treatment response. Recent findings on the IL-28B polymorphism and its application in clinical practice will also be discussed.

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Section: Il-28b and Future Therapiesmentioning

confidence: 65%

Genomics and HCV infection: Progression of fibrosis and treatment response

Estrabaud

Vidaud

Marcellin

et al. 2012

Journal of Hepatology

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“…Cell culture-adapted HCV JFH1 genotype 2A strain was propagated and infectivity titrated, as previously described previously 39 . For HCV infections, inhibitor-transfected cells were inoculated with virus at a Multiplicity of Infection (MOI) of 1.0 for 3 h and then the media was replaced.…”

Section: Methodsmentioning

confidence: 99%

“…Currently, IFN-λ-based therapy is in phase 3 clinical trials, and results from phase 2 trials have shown it to be as effective as pegIFN-α with fewer adverse effects; this suggests that IFN-λ may be a viable replacement for pegIFN-α 39,40 . myomiR inhibition may also benefit patients on IFN-free DAA regimens by increasing endogenous type III IFN production and type I IFN signaling.…”

mentioning

confidence: 99%

Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling

Jarret

McFarland

Horner

et al. 2016

Nat Med

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Hepatitis C virus (HCV) infects 200 million people globally, and 60–80% of cases persist as a chronic infection that will progress to cirrhosis and liver cancer in 2–10% of patients1–3. We recently demonstrated that HCV induces aberrant expression of two host microRNAs (miRNAs), miR-208b and miR-499a-5p, encoded by myosin genes in infected hepatocytes4. These miRNAs, along with AU-rich-element-mediated decay, suppress IFNL2 and IFNL3, members of the type III interferon (IFN) gene family, to support viral persistence. In this study, we show that miR-208b and miR-499a-5p also dampen type I IFN signaling in HCV-infected hepatocytes by directly down-regulating expression of the type I IFN receptor chain, IFNAR1. Inhibition of these miRNAs by using miRNA inhibitors during HCV infection increased expression of IFNAR1. Additionally, inhibition rescued the antiviral response to exogenous type I IFN, as measured by a marked increase in IFN-stimulated genes and a decrease in HCV load. Treatment of HCV-infected hepatocytes with type I IFN increased expression of myosins over HCV infection alone. Since these miRNAs can suppress type III IFN family members, these data collectively define a novel cross-regulation between type I and III IFNs during HCV infection.

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“…The receptors of interferon lamda are found mainly on hepatocytes. A clinical trial reported a higher RVR rate and significantly lower occurrence of adverse effects including hematologic side effects, flu-like symptoms, and muscular pain compared to peginterferon alpha 292. New DAAs being evaluated in clinical trials include NS3/4A protease inhibitors (asunaprevir, faldaprevir, ABT-450, etc.…”

Section: Treatment Of Genotypes 1 and 4 Chronic Hepatitis Cmentioning

confidence: 99%

KASL clinical practice guidelines: Management of Hepatitis C

2014

Clin Mol Hepatol

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1360 PEGYLATED INTERFERON-LAMBDA (PEGIFN-λ) SHOWS SUPERIOR VIRAL RESPONSE WITH IMPROVED SAFETY AND TOLERABILITY VERSUS PEGIFNα-2A IN HCV PATIENTS (Gl/2/3/4): EMERGE PHASE IIB THROUGH WEEK 12

Cited by 40 publications

References 0 publications

Genomics and HCV infection: Progression of fibrosis and treatment response

Genomics and HCV infection: Progression of fibrosis and treatment response

Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling

KASL clinical practice guidelines: Management of Hepatitis C

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