Please cite this article in press as: Ghobrial C, et al. Is sofosbuvir/ledipasvir safe for the hearts of children with hepatitis C virus? Dig Liver Dis (2018), https://doi.org/10.1016/j.dld.2018.09.012 ARTICLE IN PRESS G Model YDLD-3870; No. of Pages 5 Digestive and Liver Disease xxx (2018) xxx–xxx Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld Liver, Pancreas and Biliary Tract Is sofosbuvir/ledipasvir safe for the hearts of children with hepatitis C virus? Carolyne Ghobrial a,∗ , Rodina Sobhy b , Engy Mogahed a , Hala Abdullatif a , Hanaa El-Karaksy a a The Pediatric Hepatology Unit, Cairo University, Egypt b Pediatric Cardiology Unit, Pediatrics Department, Cairo University, Egypt a r t i c l e i n f o Article history: Received 26 June 2018 Received in revised form 30 August 2018 Accepted 10 September 2018 Available online xxx Keywords: Bradycardia ECG HCV Sofosbuvir a b s t r a c t Background: Symptomatic bradycardia has been reported in adults treated for chronic hepatitis C using sofosbuvir based regimens. Aim: We studied the cardiac safety of sofosbuvir/ledipasvir in Egyptian children, treated for chronic hepatitis C. Methods: The study included 40 hepatitis C virus infected children and adolescents 12–17 years old, using the combination of sofosbuvir (400 mg)/ledipasvir (90 mg) in a single oral tablet (Harvoni) taken daily for 12 weeks. All subjects underwent a baseline standard 12-lead surface Electrocardiography that was repeated at 4 and 12 weeks of therapy. Electrocardiography parameters (Heart Rate, RR interval, PR interval, QRS, QT interval, corrected QT interval, QT dispersion, JT interval, corrected JT interval, JT dispersion, Tpeak-Tend interval) were compared at the 3 different time points during antiviral therapy. Results: No symptoms related to the cardiovascular system were reported during treatment. There were no cases of symptomatic bradycardia/syncope. Heart rate was noted to be significantly lower and RR and QT intervals were significantly longer in the baseline electrocardiography. Heart rate was significantly lower and RR interval was significantly longer in patients with higher viral load. Conclusion: No adverse cardiovascular events were observed in this group of HCV infected children and adolescents treated with sofosbuvir/ledipasvir. None of the patients developed bradyarrhythmias during treatment. © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction Hepatitis C virus (HCV) infection in Egypt was reported as the highest prevalence in the world [1–3]. The most common HCV genotype in Egypt is genotype 4 (GT4) [4]. Treatment of chronic hepatitis C (CHC) slows disease progression, prevents complica- tions of cirrhosis, reduces the risk of hepatocellular carcinoma and extrahepatic complications of the virus [5]. Combination of pegy- lated interferon (PEG IFN)-2b and ribavirin (RBV) was approved by the Food and Drug Administration (FDA) in December 2008 and by the European Medicines Agency in December 2009 for treatment of children aged 3 years and older [6]. IFN-based regimens have numerous side effects, which have a negative influence on tolera- bility and adherence of patients to treatment [7]. HCV treatment in children using combination of PEG IFN-2b and RBV for 48 weeks ∗ Corresponding author at: 115 Elmanial Street, Cairo, 11451, Egypt. E-mail address: cmiga82@yahoo.com (C. Ghobrial). resulted in a 42.4% sustained virological response 24 weeks after end of treatment (SVR24) with numerous adverse effects including fever in 90% and neutropenia in more than 50% [8]. Since 2015, reports on the use of the direct acting antiviral agents (DAAs), a polymerase inhibitor such as sofosbuvir (SOF), to treat HCV showed high SVR rates [9]. In combination with other nonstructural 5A protein or protease inhibitors (such as ledipasvir [LED]), SOF-based regimens have demonstrated more than 90% SVR in patients with CHC, with much lower rates of serious side effects of less than 5% [10], resulting in good tolerability [11]. The most reported side effects occurring in 10% of patients receiving SOF/LED are headaches and fatigue; while rashes, nau- sea, diarrhea, and insomnia occur less commonly (1%–10%) [10]. Despite no major cardiovascular safety concerns with SOF in sev- eral, large-scale clinical trials [12], some case reports have recently demonstrated its possible role in cardiac bradyarrhythmias, mostly in adult patients on amiodarone; the mechanism of which is yet to be established [13,14]. https://doi.org/10.1016/j.dld.2018.09.012 1590-8658/© 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.