title: IL28B genotype predicts response to chronic hepatitis C triple therapy with telaprevir or boceprevir in treatment naïve and treatment-experienced patients other than prior partial- and null-responders.
abstract: Single nucleotide polymorphisms (SNPs) in the IL28B gene were shown to have limited utility in predicting response to telaprevir and boceprevir in treatment of chronic HCV infection in clinical trials. Data outside of the clinical trial setting are lacking. We assessed the value of single and combined IL28B SNPs rs12979860 and rs8099917 genotypes in predicting sustained virological response 12 weeks after cessation of triple therapy (SVR12) with telaprevir or boceprevir in a single-centre cohort of treatment-naïve and treatment-experienced patients with genotype 1 HCV mono-infection (n = 105). The overall SVR12 rate was 65.7%. By unadjusted bivariate logistic regression analysis, rs12979860-CC and rs8099917-TT were significantly associated with SVR12 in the subgroup of patients including all naïve patients and all treatment-experienced patients with the exception of partial- and null-responders to previous HCV therapy. The predictive value of rs12979860-CC was stronger than rs8099917-TT and only rs12979860-CC remained significantly predictive of treatment success when the two variants were assessed by adjusted logistic regression analysis in the whole study cohort. In patients presenting the rs12979860-CC variant, the additional determination of rs8099917 genotype had no value. IL28B rs12979860-CC remained significantly associated with SVR12 also in the multivariate analysis including the other baseline characteristics associated to SVR12 in the bivariate analysis (i.e., female gender, HCV genotype 1b, baseline viral load <800,000 IU/mL, advanced liver fibrosis and prior partial- or null-response to HCV therapy). Our study suggests that testing for the IL28B rs12979860 genotype may still be useful in predicting response to triple therapy with boceprevir and telaprevir in naïve patients and treatment-experienced patients other than partial and null-responders.
authors.affiliation: Department of Virology, Royal Free London NHS Foundation Trust, Pond Street, London, NW5 4AP UK.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Calisti
authors.affiliation: Department of Virology, Royal Free London NHS Foundation Trust, Pond Street, London, NW5 4AP UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Tavares
authors.affiliation: Department of Virology, Royal Free London NHS Foundation Trust, Pond Street, London, NW5 4AP UK.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Macartney
authors.affiliation: Department of Virology, Royal Free London NHS Foundation Trust, Pond Street, London, NW5 4AP UK.
authors.forename: Adele
authors.initials: A
authors.lastname: McCormick
authors.affiliation: Department of Virology, Royal Free London NHS Foundation Trust, Pond Street, London, NW5 4AP UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Labbett
authors.affiliation: The UCL Institute for Liver and Digestive Health/Royal Free London NHS Foundation Trust Viral Hepatitis Service, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: The UCL Institute for Liver and Digestive Health/Royal Free London NHS Foundation Trust Viral Hepatitis Service, London, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dusheiko
authors.affiliation: The UCL Institute for Liver and Digestive Health/Royal Free London NHS Foundation Trust Viral Hepatitis Service, London, UK.
authors.forename: William M
authors.initials: WM
authors.lastname: Rosenberg
authors.affiliation: Department of Virology, Royal Free London NHS Foundation Trust, Pond Street, London, NW5 4AP UK.
authors.forename: Tanzina
authors.initials: T
authors.lastname: Haque
keywords: Boceprevir; HCV; Hepatitis C; IL28B; Predictive value; Telaprevir