Self-reported ethnicity for HCV-1 was 79% Caucasian and 20% Asian, and for HCV-3 was 90% Caucasian and
3% Asian. Overall SVR rates were 50% for HCV-1 and 82% for HCV-3. IFNL4 gt could not be determined in 31 patients on initial testing, and DNA re-extraction and/or concentration was required. For HCV-1, IFNL4 gt frequency was 45%, 43% and 13% for TT/TT, TT/ΔG and ΔG/ΔG, and LD with rs12979860 was very high (D’ 0.98). The TT/TT IFNL4 gt was strongly associated with RVR (TT/TT 46% vs TT/ΔG 11% vs ΔG/ΔG 0%, p < 0.001) Idasanutlin chemical structure and SVR (TT/TT 78% vs TT/ΔG 28% vs ΔG/ΔG 21%, p < 0.001). In HCV-3, IFNL4 gt distribution was 42%, 43% and 15% for TT/TT, TT/ΔG and ΔG/ΔG, respectively, and LD with rs12979860 was high (D' 0.98). Numerically, RVR rates were highest in TT/TT IFNL4 gt and lowest in ΔG/ΔG IFNL4 gt patients (74% vs. 59% vs. 50%, p = 0.085). Similarly, SVR rates were highest in TT/TT patients (90%) and lower in TT/ΔG (77%) and ΔG/ΔG (72%) patients
(p = 0.117), similar to IL28B gt observations. Only 8 patients had discordant IL28B and IFNL4 gts (Table). In these patients, IFNL4 gt more accurately predicted treatment outcome. In a logistic regression model, IFNL4 gt, HCV gt, HCV RNA and ALT were independent predictors of SVR. Conclusions: This is the first independent validation study to confirm the strong association between IFNL4 genotype and PR response in HCV-1. Our data confirms that IFNL4 and IL28B gts are in strong LD. The clinical utility of IFNL4 genotype for predicting SVR was comparable BIBW2992 to that of IL28B genotype. Table: Patients with discordant IFNL4 and IL28B gts Patient no. 1 2 3 4 5 6 7 8 HCV gt 1 1 3 3 3 1 3 1 IL28B gt C/C C/C C/C C/T C/T C/T C/T T/T IFNL4 gt TT/ΔG TT/ΔG TT/ΔG TT/TT TT/TT ΔG/ΔG ΔG/ΔG TT/ΔG SVR No No No Yes Yes No Yes No AJ THOMPSON,1 S ROBERTS,2 S STRASSER,3 S BOLLIPO,4 A SLOSS,5 J WENMAN,6 W
CHENG,7 P ANGUS,8 M LEVY,9 J MITCHELL,2 medchemexpress W SIEVERT,10 B LEGGETT,11 G DORE,12 J GEORGE13 ON BEHALF OF THE ALA CLINICAL RESEARCH NETWORK 1St Vincent’s Hospital Melbourne, 2Alfred Hospital, 3Royal Prince Alfred Hospital, 4John Hunter Hospital, 5Nambour Hospital, 6Coffs Harbour Hospital, 7Royal Perth Hospital, 8Austin Hospital, 9Liverpool Hospital, 10Monash Health, 11Royal Brisbane Hospital, 12St Vincent’s Hospital Sydney, 13Westmead Hospital, Westmead Sydney Introduction: Host IL28B genotype is strongly associated with the outcome of pegylated interferon-α (pegIFN) and ribavirin (RBV) therapy for genotype 1 HCV. IL28B genotype is also strongly associated with spontaneous clearance of HCV. IL28B genotype is associated with pegIFN and RBV treatment response in patients infected with genotype 2/3 HCV as well; this association is strongest in non-RVR patients. As yet, there is no prospective data characterizing IL28B genotype frequency in the Australian genotype 2/3 HCV population.