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.

The Impact of IL28B Gene Polymorphisms on Drug Responses

“…Do đó, kiểu gen IL28B vẫn có vai trò quan trọng trong việc lựa chọn những bệnh nhân có xác suất đáp ứng cao với điều trị phác đồ kép PEG-IFN + RBV, đặc biệt là ở những quốc gia chưa được phê duyệt sử dụng các DAA hay các quốc gia đang/kém phát triển, chi phí sử dụng các DAA vượt quá khả năng của bệnh nhân [38]. Bảng tóm tắt ảnh hưởng của đa hình gen IL28B tới phác đồ 3 thuốc (PEG-IFN + RBV + DAA) trong điều trị viêm gan C mạn tính được trình bày trong Bảng 4; [ [39][40][41] rs8099917 Kiểu gen TT cho tỷ lệ đạt SVR cao hơn so với kiểu gen TG/GG. Đa hình rs8099917 liên quan đến SVR ở bệnh nhân HCV 1, 3 và 4, không cho thấy mối liên quan ở HCV 2.…”

“…[ [40][41][42] Phác đồ PEG-IFN + RBV+ simprevir rs12979860 Kiểu gen CC có liên quan đến việc tăng đáp ứng điều trị so với kiểu gen CT + TT. [43] rs8099917 Ở bệnh nhân chưa từng điều trị trước đây hoặc tái phát virut, kiểu gen TT cho khả năng dự đoán SVR tốt hơn so với kiểu gen TG/GG.…”

The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort

“…The most favorable treatment outcome was obtained with SNPs, in decreasing order, CC, CT, and TT ( 19 ). Although a specific study was not carried out, there were robust data that showed a better outcome for the patients with CC SNP compared with non-CC also in the PI-triple setting ( 11 , 20 , 21 ).…”

The distribution of IL28B polymorphism (rs12979860) and its effect on the response to treatment in patient with chronic hepatitis C virus in Aydın province

“…Bu çalışmada, Adnan Menderes Üniversitesi Uygulama ve Araştırma Hastanesi'nde takip edilmekte olan kronik HCV hastalarında antiviral tedaviye erken ve kalıcı viral yanıt ile IL-28B (rs12979860) polimorfizmi arasındaki ilişkinin araştırılması amaçlanmıştır. (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) . Bazı çalışmalarda ise, IL28B (rs12979860) genotipi ile KVC gelişimi arasında anlamlı bir ilişki gösterilememiştir (26,27) .…”