IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C

Asselah, Tarik; Muynck, Simon De; Broët, Philippe; Masliah‐Planchon, Julien; Blanluet, Maud; Bièche, Ivan; Lapalus, Martine; Martinot–Peignoux, Michelle; Lada, Olivier; Estrabaud, Emilie; Zhang, Qian; Ray, Ahmed El; Vidaud, Dominique; Ripault, Marie–Pierre; Boyer, Nathalie; Bédossa, Pierre; Valla, Dominique; Vidaud, Michel; Marcellin, Patrick

doi:10.1016/j.jhep.2011.09.008

Cited by 169 publications

(157 citation statements)

References 28 publications

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“…According, they concluded that IL-28B genotype can't be considered a determinant for the development of advanced liver fibrosis. Similarly, (Asselah et al, 2012) were not able to find any significant relationship between IL28B rs12979860 polymorphism and fibrosis stage or disease severity, though they reported a significant correlation between IL28B rs12979860 polymorphism and treatment. However, some recent studies showed that the IL-28B rs12979860 T/T genotype is an independent predictor of a higher fibrosis staging score compared to the CC or CT genotypes (Agundez et al, 2010;Falleti et al, 2011).…”

Section: Discussionmentioning

confidence: 84%

IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCV

Zekri¹,

Salama²,

Medhat³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

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Section: Discussionmentioning

confidence: 84%

IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCV

Zekri¹,

Salama²,

Medhat³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Even though IL28B has been found to be associated with SVR in some reports concerning genotype 4 as well [33][34][35], it still remains unclear whether the difference in SVR observed between endemic and European studies is related to ethnicity, HCV subtype, the mode of transmission or the IL-28B genotype [1,36]. Furthermore, distribution of IL28B polymorphisms varies between different populations worldwide and could help explain the heterogeneity in response to treatment in different ethnic or racial groups, but this still needs to be confirmed in large epidemiological studies in the Middle East and Europe.…”

Section: Discussionmentioning

confidence: 97%

“…Recently, the identification of interleukin 28B (IL28B) polymorphism has proved to be a significant determinant of HCV response to interferon-based therapies [1,33]. Even though IL28B has been found to be associated with SVR in some reports concerning genotype 4 as well [33][34][35], it still remains unclear whether the difference in SVR observed between endemic and European studies is related to ethnicity, HCV subtype, the mode of transmission or the IL-28B genotype [1,36].…”

Section: Discussionmentioning

confidence: 99%

Genotype 4 Hepatitis C Virus Responds Worse than Genotype 1 to 48-Week Combination Treatment with Pegylated Interferon Alpha Plus Ribavirin: a Greek Multi-Centered Study

Savvidou¹,

Dimitrios²,

Papatheodoridis³

et al. 2014

J Antivir Antiretrovir

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“…There is a major medical need since standard of care remains PegIFN-RBV for 48 weeks with low SVR in ''difficult-to-cure'' patient populations (IFNL3 non CC; patients with cirrhosis, experienced patients, etc.) [6]. We urge for studies in G4 HCV, naïve but also experienced patients.…”

mentioning

confidence: 99%

“…We have to recall obvious evidence: G2 HCV is not G3, and we need separate studies. In past PegIFN/RBV dual therapy, for statistical issues, HCV G1 and G4, and HCV G2 and G3, were respectively pooled [6]. For DAAs, we need an individual study for each genotype.…”

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confidence: 99%

Sofosbuvir-based interferon-free therapy for patients with HCV infection

Asselah

2013

Journal of Hepatology

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Background: The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection. Methods: We provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks. Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment. We report the rate of sustained virologic response 24 weeks after therapy. Results: Of the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks. For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy. Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia. Conclusions: Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences; ClinicalTrials.gov number, NCT01260350). Ó 2013 European Association for the Study of the Liver. Published by Elsevier B.V.For the treatment of HCV infection, several direct-acting antivirals (DAAs), including NS3 protease inhibitors, nucleoside/ nucleotide analogues and non-nucleoside inhibitors of the RNAdependent RNA polymerase, and NS5A inhibitors, are under development [1]. Among them, sofosbuvir is a potent HCV-specific nucleotide analog (chain terminator). It is given orally, once daily, without food effect. So far, no safety signal in preclinical/ clinical studies has been observed with this compound. Sofosbuvir has a high barrier to resistance with no virologic breakthrough to date. It has a pangenotypic antiviral effect, although it might be less efficient in genotype 3 (G3).The ELECTRON study goal was to evaluate the safety and efficacy of sofosbuvir as a backbone of co...

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IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C

Cited by 169 publications

References 28 publications

IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCV

IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCV

Genotype 4 Hepatitis C Virus Responds Worse than Genotype 1 to 48-Week Combination Treatment with Pegylated Interferon Alpha Plus Ribavirin: a Greek Multi-Centered Study

Sofosbuvir-based interferon-free therapy for patients with HCV infection

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