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800A AASLD ABSTRACTS HEPATOLOGY, October, 2015 1193 ITPA polymorphisms are predictors of anemia but no contribution to outcomes in chronic hepatitis C patients who treated with interferon plus ribavirin Xiumei Chi 1 , Mo-li Wang 3 , Yu Pan 1 , Jing Jiang 2 , Hongqing Yan 1 , Ruihong Wu 1 , Xiaomei Wang 1 , Junqi Niu 1 ; 1 Hepatology, The first hospital of Jilin University, Changchun, China; 2 Epidemoology, The first hospital of Jilin University, Changchun, China; 3 The fourth hospital of Jilin University, Changchun, China Background and Aims: In a genome-wide association study of patients being treated for chronic hepatitis C (HCV), two single nucleotide polymorphisms (SNPs) within or adjacent to the inosine triphosphatase (ITPA) gene (rs1127354, rs6051702) were shown to protect against ribavirin induced hemolytic anemia during early stages of treatment. We then evaluated these polymorphisms/variants as predictors of anemia or treatment outcomes (SVR) in a large cohort of naive HCV patients who were treated with interferon plus ribavirin. Methods: Genetic material was available from 351 HCV patients. These patients were enrolled in the first hospital of Jilin University who underwent interferon plus ribavirin combination therapy and they had no history of any other interferon-based therapy. rs6051702 in C20orf194, rs1127354 in ITPA and rs8099917 in IL-28B were genotyped and tested for their association with hemoglobin (Hb) reduction during treatment and with treatment outcomes. A stepwise multivariate regression analysis was performed to identify factors associated with outcome of the therapy. Results: The ITPA rs1127354 minor variants were significantly associated with protection against reduction Hb level at week 4 (p=2.65×10 -4 during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.861). rs1127354 was strongly and independently associated with protection from quantitative Hb reduction at week 4. The minor alleles of each variant protected against HB reduction. The ITPase deficiency genotype was associated with lower rates of anemia over the entire treatment period (72 weeks). No association with sustained virological response (SVR) was observed. Conclusion: ITPA polymorphisms influences hemoglobin levels during ribavirin combination therapy. rs1127354 was conrmed to be a useful predictor of ribavirin-induced anemia in HCV patients but not a predictive factor for treatment outcomes. Disclosures: The following authors have nothing to disclose: Xiumei Chi, Mo-li Wang, Yu Pan, Jing Jiang, Hongqing Yan, Ruihong Wu, Xiaomei Wang, Junqi Niu 1194 Cardiac arrhythmia in patients with chronic hepatitis C virus infection treated with sofosbuvir-including regimen Hélène Fontaine 1,2 , Arnaud Lazarus 3,4 , Caroline Pecriaux 5 , François Bagate 3 , Philippe Sultanik 1,2 , Estelle Boueyre 1,2 , Marion Corouge 1,2 , Vincent Mallet 1,2 , Anaïs Vallet-Pichard 1,2 , Philippe Sogni 1,2 , Denis Duboc 3 , Stanislas Pol 1,2 ; 1 Hepatology Unit, Cochin Hospital, Paris, France; 2 Université Paris Descartes, INSERM USM20, Institut Pasteur et Assistance Pubique - Hôpitaux de Paris, Paris, France; 3 Cardiology Unit, Hôpital Cochin, Assistance Publique -Hôpitaux de Paris, Paris, France; 4 Rhythmology Unit, Clinique Ambroise Paré, Neuilly Sur Seine, France; 5 Unité de Pharmacovigilance, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France Introduction: Treatment of chronic hepatitis C virus (HCV) infection has dramatically improved since the advent of direct anti-viral agents, including Sofosbuvir. Sustained virological response, which corresponds to a viral cure, is achievable in more than 90 % of patients. To date, several thousands of patients have been treated with Sofosbuvir-based regimens worldwide. Since their approval in France, oral anti-viral therapies were prescribed for patients with complications, including cirrhosis and life-threatening extra-hepatic manifestations. Methods: We analyzed prospectively the incidence of arrhythmias and conduction disorder in a cohort of patients treated by Sofosbuvir (new antiviral HCV) in our hospital from January 2, 2014 to December, 31, 2014. Results: We observed five cases (1.2 %) of severe arrhythmia, including three cardiac conduction defects, within the first days of Sosfobuvir-based therapy among 415 patients who had been treated in our unit. There were two females and three males. The median age was 58 (50-75) years. Two patients were co-infected with HIV. Arrhythmia relapsed when Sofosbuvir was reintroduced in one patient. Among the 3 conduction disorders, two patients were treated with beta-blocker and another with amiodarone. A pacemaker was implanted in all 3 patients with conduction disorders. The three patients who underwent a pacemaker implantation were not pacemaker-dependent on the controls after stopping antiviral treatments. Conclusion: Sofosbuvir seems to have cardiac toxicity. The mechanisme underlying Sofosbuvir cardiotoxicity has to be determined. A particular attention should be given to patients with a medical history of rhythm or conduction abnormalities, including careful monitoring (e.g., Holter ECG recordings) of cardiac rhythm during the first days of Sofosbuvir therapy. Disclosures: Hélène Fontaine - Board Membership: Gilead, BMS, Janssen, Abbvie; Speaking and Teaching: Gilead, BMS, Janssen, Abbvie, MSD Arnaud Lazarus - Board Membership: Boston Scientific, Medtronic; Consulting: Sorin Group; Employment: Biotronik Anaïs Vallet-Pichard - Independent Contractor: Schering Plough, Gilead, BMS, Roche Philippe Sogni - Board Membership: BMS, Gilead; Consulting: Gilead, Roche, MSD, BMS, Janssen, Mayoli-Spindler Stanislas Pol - Board Membership: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/Research Support: Glaxo Smith Kline, Gilead, Roche, MSD; Speaking and Teaching: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis The following authors have nothing to disclose: Caroline Pecriaux, François Bagate, Philippe Sultanik, Estelle Boueyre, Marion Corouge, Vincent Mallet, Denis Duboc 1195 Utility of acoustic radiation force impulse (ARFI) for predicting treatment response of patients with chronic hepatitis C receiving triple therapy with protease inhibitor plus pegylated interferon and ribavirin Ryoko Yamada 1 , Naoki Hiramatsu 1 , Tsugiko Oze 1 , Ayako Urabe 1 , Yuki Tahata 1 , Naoki Morishita 1 , Takayuki Yakushijin 1 , Yuichi Yoshida 1 , Tomohide Tatsumi 1 , Yasuharu Imai 2 , Tetsuo Takehara 1 ; 1 Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan; 2 Ikeda Municipal Hospital, Ikeda, Japan Background & Aim: With interferon-based therapy, liver fibrosis has been reported to correlate with the virologic response in patients with chronic hepatitis C (CH-C). Acoustic radiation force impulse (ARFI) is known as a non-invasive procedure for assessment of liver fibrosis. In this study, we investigated the utility of ARFI for CH-C patients receiving triple therapy with protease inhibitor (PI) plus pegylated interferon (Peg-IFN) and ribavirin (RBV). Patients & Methods: A total of 105 genotype 1 CH-C patients were enrolled. They started triple therapy (telaprevir/simeprevir, 26/79) between February 2011 and June 2014, following liver biopsy and ARFI assessment. The base-
HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 801A line characteristics were as follows: age, 60.9 ± 10.0 years old; median HCV RNA, 6.6 log IU/mL; platelet count, 15.8 ± 5.1 x10 4 /mm 3 ; ALT, 56.4 ± 42.0 IU/L; Vs value, 1.47 ± 0.46 m/sec; Fibrosis score (F1/2/3/4), 55/18/15/10. Single nucleotide polymorphisms located near the IL28B (rs8099917) gene were determined using a real-time PCR system. Results: Vs values at baseline showed positive correlation with Fibrosis score (p
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1312A AUTHOR INDEX HEPATOLOGY, Octo
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1366A CATEGORY INDEX HEPATOLOGY, Oc
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