The design and primary outcomes of the VIRAHEP-C trial have been reported elsewhere.8 Adults who were treatment-naïve, infected with genotype 1, had detectable HCV RNA, and had histological evidence of chronic HCV were eligible to participate. Patients were classified by race as either African American or Caucasian, and by ethnicity as either Hispanic or non-Hispanic, based on self-report. All participants were required to have

been born in the United States. From eight clinical centers across the United States, 401 patients were enrolled and began therapy between July 2002 and December 2003. For the present study, serum samples were acquired from a subset of 272 patients from the total VIRAHEP-C cohort, comprising 157 responders Autophagy activator (104 CA, 53 AA) and 115 nonresponders (34 CA, 81 AA). All specimens analyzed were obtained under Institutional Review Board–approved protocols for which participants

provided written informed consent, including consent for genetic testing. Patients received peginterferon alfa-2a (Pegasys; Roche Pharmaceuticals, Nutley, NJ) 180 μg/week and ribavirin (Copegus; Roche Pharmaceuticals) 1,000-1,200 mg/day for at least 24 weeks. Patients who became HCV RNA–negative by week 24 continued treatment for a total of 48 weeks, whereas patients who remained HCV RNA–positive stopped treatment and were considered nonresponders. The primary endpoint of the trial was SVR, defined as the absence of detectable HCV RNA for at least 24 weeks after stopping therapy. HCV RNA testing was performed at a central laboratory (SeraCare BioServices, Gaithersburg, MD) NVP-BKM120 datasheet using the Cobas Amplicor Assay (sensitivity, 50 IU/mL; Roche Molecular Diagnostics, Alameda, CA). Selected samples were tested for HCV RNA levels using the Cobas Amplicor Monitor Assay and for HCV RNA genotype using Carnitine palmitoyltransferase II the Versant HCV Genotype Assay (Bayer, Tarrytown, NY). All patients had undergone liver biopsy within 18 months of screening, and

the biopsy specimens were assessed by a blinded central pathologist. All biopsies were assessed for severity of hepatitis C by grading the inflammation and staging the fibrosis using Ishak’s modified histological activity index. IP-10 was measured in serum samples collected at baseline, prior to initiation of treatment, using the commercially available Quantikine human CXCL10/IP-10 immunoassay (R&D Systems). All samples were diluted 1:2 and analyzed in duplicate. The linear dynamic range of the IP-10 measurement in this assay was 8-500 pg/mL, with a detection limit at 7.8 pg/mL. Samples with IP-10 concentration above 1,000 pg/mL were diluted 1:5 and reanalyzed. The IL28B polymorphic marker rs12979860 was analyzed using the ABI TaqMan allelic discrimination kit and the ABI7900HT Sequence Detection System (Applied Biosystems) as described by Thomas and colleagues.