High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial)

Chevaliez, Stéphane; Hézode, Christophe; Soulier, Alexandre; Costes, Bruno; Bouvier‐Alias, Magali; Rouanet, Stéphanie; Foucher, Juliette; Bronowicki, Jean–Pierre; Tran, Albert; Rosa, Isabelle; Mathurin, Philippe; Alric, Laurent; Leroy, Vincent; Couzigou, Patrice; Mallat, Ariane; Charafeddine, Mariem; Babany, G; Pawlotsky, Jean‐Michel

doi:10.1053/j.gastro.2011.03.039

Cited by 25 publications

(21 citation statements)

References 23 publications

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“…The rs12979860 polymorphic site distribution difference between the HCV RNA<6×10 5 group and ≥6×10 5 group was compared. C/C frequency in those two groups were 86.7% and 82.8%, respectively, and C/T frequency were 13.3% and 17.2%, the IL-28B genotype distribution had no association with viral load(P=0.830), which was similar with previous results 27, 28. The main focus of this study was the potential clinical applicability of IL-28B genotype.…”

Section: Discussionsupporting

confidence: 88%

IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C

Zhong¹,

Zhang²,

Shi³

et al. 2016

Int. J. Biol. Sci.

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Clinical data on children with chronic hepatitis C (CHC) remain extremely limited. This study investigated sustained virologic response (SVR) to alfa-interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection-acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them were male (65.6%) and 53 were female (34.4%), and they were treated with alfa-interferon at a dose of 1-5 MIU/m2 3 times weekly plus oral RBV (15 mg/kg/day) for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a, 15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with undecided type. There was no significant statistical difference in SVR between male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype 1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT≤40U/L group(96.7% vs 96.8%, p=1.000), AST>40U/L group and AST≤40U/L group(95.9% vs 98.2%, p=0.654) as well as lower baseline viral load group (<6×105 IU/ml) and higher baseline viral load group(≥6×105 IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia, hemoglobin concentration decrease, fever, platelet count decrease and rash were 8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%) individuals developed thyroid autoantibodies. The SVR was higher in patients with IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable for predicting antiviral efficacy in children with CHC. It is inappropriate to take the increase of ALT level as an essential indicator for antiviral treatment in children aged 1-6 years.

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Section: Discussionsupporting

confidence: 88%

IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C

Zhong¹,

Zhang²,

Shi³

et al. 2016

Int. J. Biol. Sci.

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“…Also, it would be interesting to study whether the impairment of antiviral effectiveness and higher occurrence of PK‐related viral rebound in patients with significant fibrosis could be minimized by using higher doses of Peg‐IFN and/or ribavirin. Interestingly, an improvement of the virological response has recently been reported in a population of nonresponders to Peg‐IFN with a high proportion of cirrhosis (45%) retreated with 360 μg/week of Peg‐IFN and/or higher doses of ribavirin [41]. Although this antiviral strategy eventually failed to improve SVR [41], the improvement of the antiviral effectiveness may still be valuable to limit the outgrowth of resistant virus in a tritherapy combination that includes a protease inhibitor.…”

Section: Discussionmentioning

confidence: 99%

The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1–infected patients treated with Peg‐IFN‐alfa‐2a and ribavirin

Guedj

Negro³

et al. 2011

Journal of Viral Hepatitis

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Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1-infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, ≥0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.

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“…Currently, the polymorphism is analyzed mostly by custom-designed TaqMan assays [7-9]. These assays as well as direct sequencing and other assays [10-12] allow for the screening of patient samples.…”

Section: Introductionmentioning

confidence: 99%

A Fast and Cost-Effective Method for Identifying a Polymorphism of Interleukin 28B Related to Hepatitis C

et al. 2013

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Approximately 170 million people are chronic carriers of hepatitis C virus (HCV). Patients with chronic hepatitis C are currently treated with pegylated interferon and ribavirin (PEG-IFN/RBV). A genome-wide association with PEG-IFN/RBV treatment response and a single nucleotide polymorphism (rs12979860) has been identified near the interleukin 28B gene that encodes interferon-λ-3. In this paper, we describe an innovative, fast, and low-cost multiplex polymerase chain reaction with confronting two-pair primers that detects the rs12979860 polymorphism. The assay is internally controlled and does not require the use of restriction endonucleases or special equipment. Moreover, the assay decreases costs, being about 40% cheaper than direct sequencing methods.

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High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial)

Cited by 25 publications

References 23 publications

IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C

IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C

The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1–infected patients treated with Peg‐IFN‐alfa‐2a and ribavirin

A Fast and Cost-Effective Method for Identifying a Polymorphism of Interleukin 28B Related to Hepatitis C

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