13) had a highly significant impact on SVR rates in HCV genotype 1 patients enrolled in a large, randomized, multicenter trial (IDEAL).13 Patients with a homozygous C/C genotype at this locus had significantly higher SVR rates than those who carried the T allele.13 Spontaneous clearance of

acute HCV infection was also shown to be more likely in individuals with the C/C genotype.14 These findings have since been confirmed in several independent analyses in genotype 1 patients,15-17 and evidence is accumulating for a role of IL28B genotype in the response to therapy in patients infected with other HCV genotypes.18-21 Determination of rs12979860 genotype is thus a useful prognostic BGJ398 supplier factor in patients infected with HCV genotype 1 and, with the availability of a commercial test in the U.S., PI3K Inhibitor Library it is now a tool that can be used in routine clinical practice for informing treatment decisions.22

Unfortunately, the rs12979860 genotype does not have a 100% positive predictive value for SVR; indeed, RVR is a better predictor of SVR than IL28B genotype.16, 17 It remains to be determined whether the combination of rs12979860 genotype and early viral kinetics can be used to optimize treatment duration and SVR rates. The database from a recently completed, large, randomized, multicenter trial in which the primary objective was to compare relapse rates in patients randomized to 48 and 72 weeks of treatment provides the opportunity to examine the impact of the rs12979860 genotype on outcomes in HCV genotype 1 and 4 patients undergoing response-guided therapy.12 EVR, early virologic response; GWAS, genome-wide association study; HCV, hepatitis

C virus; RVR, rapid virologic response; SNP, single nucleotide polymorphism; SVR, sustained virologic response. This Austrian multicenter study included treatment-naive chronic hepatitis patients with HCV genotype 1 or 4. All genotype 1 patients were Caucasians; all genotype 4 patients originated from Egypt. The study design and primary results of the study are published elsewhere.3, 12 Briefly, all patients initiated treatment with 180 μg/week peginterferon alpha-2a (PEGASYS, Roche, Basel, Switzerland) and ribavirin 1,000 mg/day (body weight ≤75 medchemexpress kg) or 1,200 mg/day (body weight >75 kg) (COPEGUS, Roche). The duration of treatment was determined on the basis of the on-treatment virologic response at treatment weeks 4 and 12. All patients with undetectable HCV RNA (<50 IU/mL by qualitative polymerase chain reaction [PCR] assay, COBAS AMPLICOR HCV Test, v. 2.0, Roche Diagnostics, Branchburg, NJ) at week 4 (RVR) were treated for 24 weeks (group D). Patients with detectable HCV RNA (≥50 IU/mL) at week 4 and either undetectable HCV RNA or ≥2 log10 drop in HCV RNA at week 12 (early virologic response [EVR]) were randomized to complete a total of 48 weeks (group A) or 72 weeks (group B) of treatment.