This suggested that the SVR benefit reflects RBV pharmacokinetics rather than the Hb level per se. This hypothesis was tested in a patient subset (n = 203) in which plasma RBV levels were found to be associated with both Hb reduction and SVR. However RBV levels were not associated with ITPase activity. In a multivariable

logistic regression model including RBV level, the association between nadir Hb and SVR was attenuated. Conclusion: ITPase deficiency protects against RBV-haemolysis, but is not associated with SVR. The association between Hb reduction and SVR is independent of ITPase deficiency. Our data confirm that the relationship between Hb decline and SVR is not mechanistic, but is explained by RBV pharmacokinetics. The data emphasize the importance of adequate RBV exposure during antiviral therapy for HCV. 1 Fellay J. Nature 2010; 464:405; 2 Sievert W. Hepatol 2011; 53:1109; 3 Sulkowski Gastro 2010; 139:1602; Selleck Z VAD FMK 4 Thompson AJ. Gastro 2010; 139:1181 JA HOLMES,1 A MANGIA,2 PJ CLARK,3 DM ISER,1 T NGUYEN,1 SJ BELL,1 M RYAN,1 S BONANZINGA,4 PV DESMOND,1 D PETRUZZELLIS,2 DS BOWDEN,4 AJ THOMPSON1 1St. Vincent’s Hospital, Melbourne, VIC, Australia, 2IRCCS ‘Casa Sollievo della Sofferenza’ Hospital, San Giovanni PD0325901 solubility dmso Rotondo, Italy, 3Princess Alexandra Hospital, Brisbane, QLD, Australia, 4Victorian Infectious Diseases Reference Laboratory, North Melbourne, VIC Australia

Background: Anaemia is a frequent adverse event associated RAS p21 protein activator 1 with protease inhibitor (PI) therapy for HCV, and is additional to that observed with pegylated-interferon (peg-IFN) and ribavirin (RBV). Management may require blood

transfusions (BT) or RBV dose reduction which may compromise efficacy and tolerability of treatment. Identification of patients at highest risk for severe anaemia would be useful. ITPA polymorphisms, predicting ITPase deficiency, have been associated with protection from ribavirin-induced haemolytic anaemia. We evaluated the association between ITPA polymorphisms and anaemia during PI therapy in a real-world multi-centre cohort. Methods: Patients from Australia and Europe who had received at least 4 weeks of PI (Boceprevir or Telaprevir) in combination with weight-based RBV and peg-IFN were included. Anaemia management was at the discretion of the treating clinician. Haemoglobin (Hb) was evaluated at baseline and 4 weeks after the introduction of PI. ITPA variants (rs7270101 and rs1127354) were determined using the TaqMan Allelic Discrimination Kit, and predicted ITPase activity was estimated as previously described†. ITPase activity was then correlated with week 4 Hb reduction (>30 g/L) after PI commencement (PI anaemia). Results: 164 patients were included: median age was 54.6 years, 42% female, 50% received boceprevir PI therapy, and 83% had METAVIR stage F3-4. Median baseline Hb was 151.