Deep-sequencing study of HCV G4a resistance-associated substitutions in Egyptian patients failing DAA treatment

Abstract

Fatma Amer,1 Monkez M Yousif,2 Noha M Hammad,1 Damir Garcia-Cehic,3,4 Josep Gregori,3–5 Ariadna Rando-Segura,6 Leonardo Nieto-Aponte,6 Juan Ignacio Esteban,3,4 Francisco Rodriguez-Frias,4,6 Josep Quer3,4 1Department of Medical Microbiology and Immunology, Faculty of Medicine, Medical College, Zagazig University, Zagazig, Egypt; 2Internal Medicine Department , Faculty of Medicine, Medical College, Zagazig University, Zagazig, Egypt; 3Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d’Hebron Institut Recerca (VHIR)-Hospital Universitari Vall d’Hebron (HUVH), Barcelona 08035, Spain; 4Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid 28029, Spain; 5Business Development Department, Roche Diagnostics SL, Sant Cugat del Vallès, Barcelona 08174, Spain; 6Liver Pathology Unit, Department of Biochemistry and Microbiology, HUVH, Barcelona 08035, SpainCorrespondence: Josep QuerLiver Unit, Liver Disease Laboratory-Viral Hepatitis, Internal Medicine Department, Vall d’Hebron Institut Recerca (VHIR-HUVH), Barcelona 08035, SpainTel [phone]Email [email protected] AmerMedical Microbiology and Immunology Department, Zagazig Faculty of Medicine, 9A, Road 275, New Maadi, Cairo, Zagazig, EgyptTel [phone]Email [email protected]: To study resistance-associated substitutions using next-generation sequencing in Egyptian hepatitis C virus-infected patients failing direct-acting antiviral treatment.Methods: The current study describes three cases of treatment failure in patients referred to Zagazig Viral Hepatitis Treatment Center (ZVHTC), Sharkia Governorate, Egypt. RAS were identified and characterized using deep sequencing. The first patient had breakthrough while receiving a daclatasvir (DCV)+sofosbuvir (SOF) regimen, patient 2 relapsed after treatment with DCV+SOF+ribavirin (RBV), and patient 3 relapsed after DCV+SOF therapy. A serum sample was collected from each patient at failure and sent to Vall d’Hebron Research Institute at Hospital Universitari Vall d’Hebron in Barcelona (Spain) for deep-sequencing study to identify and characterize the RAS present in the samples.Results: The following were identified: L28M, L30S and L28M+L30S in patient 1, L30R in patient 2, and R155C, D168E, L28M, L30H, L30S, L28M+L30H, and L28M+L30S in patient 3.Conclusion: To the best of our knowledge, this is the first report from Egypt of patients failing DAA-based therapy, describing the associated RAS. This information will be of help to understand the natural history of HCV in Egyptian patients and guide the proper choice of retreatment protocols.Keywords: resistance-associated substitutions, RAS, subtype 4a, treatment failure, Egypt, direct acting antivirals, DAA

Keywords

• resistance-associated substitutions (RAS)
• subtype 4a
• treatment failure
• Egypt
• direct acting antivirals (DAA)