Inosine triphosphatase (ITPA) single nucleotide polymorphism (SNP

Inosine triphosphatase (ITPA) single nucleotide polymorphism (SNP) rs1127354, causing ITPase deficiency, was found to be associated with protection from RBV-induced

anemia and to decrease the need for RBV dose reduction, but not to be associated with clinical outcome.[22-25] The present study was performed to identify that factors, including interleukin-28B (IL28B) and ITPA genotype, associated with the outcome of extended 72-week treatment in patients with HCV genotype 1 who had LVR to PEG-IFN and RBV. A total of 471 patients were recruited at Osaka City University Hospital between December 2004 and June 2012. The flow of patients through the trial is presented in Figure 1. Sixty-six patients with HCV genotype 1 who were treated with PEG-IFN alpha 2a (Pegasys; Chugai Pharmaceutical Co., Ltd, Tokyo, Japan) or 2b (Pegintron; MSD, Osaka, Japan) and RBV (Rebetol, MSD) combination therapy were enrolled click here in this study. All patients had a viral load of > 105 IU/mL according to COBAS Amplicor HCV Monitor test, version 2.0 (Roche Diagnostics, Branchburg, NJ, USA), or a viral load of > 5 log copies/mL as determined by COBAS TaqMan HCV test (Roche Diagnostics). HCV RNA levels were

investigated before and every 4 weeks after the start of treatment. All patients gave written informed consent to participate in this PCI-32765 in vivo study, in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and according to the process approved by the ethical committee of Osaka City University, Graduate School of Medicine. Only the patients who completed 72-week combination therapy without discontinuation and in whom HCV RNA was detected on week 12 but not on weeks 13–36 were enrolled in this selleck inhibitor study. Exclusion criteria included a history or evidence of a serious chronic or poorly controlled medical or psychiatric condition, infection with human immunodeficiency

virus or hepatitis B virus, and receipt of systemic immunomodulatory or antineoplastic therapy within the previous 6 months. Pregnant or breastfeeding women and partners of pregnant women were also excluded. The following factors were analyzed to determine whether they were related to the efficacy of combination therapy: patient age, gender, pretreatment biochemical parameters, such as neutrophil and platelet counts, hemoglobin concentration, levels of alanine transaminase, creatinine, HCV viral load, histopathological evaluation of hepatitis activity and hepatic fibrosis according to the METAVIR scoring system, total doses of PEG-IFN and RBV, and serum RBV concentration at week 44. The initial dose of PEG-IFN alpha 2a was 180 μg per week, and that of PEG-IFN alpha 2b was 1.5 μg per kg body weight per week. The initial dose of RBV was 400, 600, 800, or 1000 mg/day for patients weighing < 40 kg, 40–60 kg, 60–80 kg, or > 80 kg, respectively.

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