8, 10-12 Chemokines and cytokines are attractive as potential markers for treatment outcome because they are regulators of immunity and inflammation in HCV infection. Many are modulated by exogenous interferon and play critical roles in viral clearance. Responders tend to have a lower baseline activation of

the immune system prior to treatment that is more markedly induced in response to IFN treatment.13-15 Galunisertib Several studies have shown that the non-ELR CXC chemokine interferon-γ–inducible protein-10 (IP-10 or CXCL10) may be a prognostic marker for HCV treatment outcome in genotype 1 infection.15-20 Elevated pretreatment IP-10 levels correlate with

nonresponse to PEG-IFN and ribavirin therapy, although this relationship has not been validated in AA patients. More recently, data have been published on a gene polymorphism (rs12979860) upstream of IL28B that is favorably associated with treatment response to PEG-IFN and ribavirin in both AA and CA patients.21 Regardless of race, carriage of the C allele increases treatment response rates, with CC genotype patients having the highest SVR rates, CT genotype patients having intermediate rates, and TT genotype patients having the lowest rates.21 This favorable genotype is seen more frequently in Caucasian AZD9291 clinical trial patients and likely explains approximately half of the difference

in response between AA and CA of European ancestry. The IL28B gene encodes IFN-λ3, a type III IFN induced by viral infections.22, 23 Although the mechanism underlying the association of IL28B genotype and HCV clearance has not been elucidated, modulation of the innate immune response likely plays a role in controlling this viral infection. IL28B genotyping may provide useful pretreatment stratification of patients for HCV treatment in the future, but it does not completely explain response discrepancies between AA and CA patients. In this study, we measured pretreatment IP-10 levels in serum samples from 272 patients Demeclocycline in the VIRAHEP-C cohort (115 nonresponders and 157 responders). This analysis demonstrated IP-10 to be equally predictive of SVR both in CA and AA patients. We then assessed the combination of pretreatment serum IP-10 levels with IL28B genotype as predictors of response to PEG-IFN and ribavirin in this cohort. AA, African-Americans; AUC, area under the curve; CA, Caucasian Americans; HCV, hepatitis C virus; IP-10, interferon-γ–inducible protein-10; ISG, interferon-stimulating genes; PEG-IFN, peginterferon; ROC, receiver operating characteristic; SVR, sustained virological response; VIRAHEP-C, The Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C.