[29] Dose reductions for hematological

side-effects were based mainly on the information supplied by each drug manufacturer. Grade 2 or higher adverse events, such as malaise, fever, anorexia and light-headedness, resulted in TVR reductions of 750 mg/day, PEG IFN reductions of 10–20 μg/week, and RBV reductions of 200 mg/day as soon as possible, until symptom severity decreased to grade 1 or below. None of the patients received erythropoietin or granulocyte-macrophage colony-stimulating factor during treatment. Patients with grade 1 (several sites or localized see more to one site) or 2 (diffuse skin eruption involving up to 50% of the body surface) dermatological adverse events were managed at the discretion of the physicians at each hospital. TVR was discontinued in patients who experienced a progressive grade 3 dermatological adverse event (rash with the appearance of substantial systemic signs or symptoms or involving >50% of the body surface), but these patients continued to receive PEG IFN-α-2b and RBV, if possible. Hepatitis C virus RNA concentrations were measured using the TaqMan HCV assay (COBAS TaqMan HCV assay; Roche Molecular Diagnostics, Tokyo, Japan) with lower and upper limits of quantification of 15 IU/mL and 6.9 × 107 IU/mL (range, 1.2–7.8 log IU/mL), respectively. HCV genotype

was determined using a HCV Genotype Primer Kit (Institute of Immunology, Tokyo, Japan). Amino acid substitutions in core 70/91 were assayed as described.[30] Previous virological responses to IFN-based therapy included prior relapse, undetectable HCV RNA at the end of treatment but detectable HCV RNA 24 weeks or Gefitinib molecular weight less later and the reappearance of HCV RNA at any time during treatment after a virological response (breakthrough). Patients whose HCV RNA never became undetectable during treatment were defined as non-responders. Rapid virological response (RVR) was defined as undetectable serum HCV RNA at week 4 of treatment. End of treatment response (ETR) was defined as undetectable HCV

RNA at the end of therapy. SVR12 was defined as undetectable HCV RNA 12 weeks after the completion of treatment.[31] All methods of assessing treatment efficacy were defined according to guidelines.[32, 33] Even if treatment was discontinued before the assigned schedule because of side-effects or non-compliance with therapy, patients were considered Resminostat SVR12 if serum HCV RNA was undetectable at 12 weeks of follow up. During follow up, clinical, biochemical and qualitative serum HCV RNA parameters were determined every 1–3 months. Genetic polymorphisms in tagged SNP located near IL28B (rs8099917) were determined by direct sequencing of polymerase chain reaction-amplified DNA. IP-10 was measured in serum samples collected at baseline, prior to initiation of TVR-based triple therapy, using commercially available Quantikine human CXCL10/IP-10 immunoassay kits (R&D Systems, Minneapolis, MN, USA).