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Short article: Retreatment of chronic hepatitis C virus infection after unsuccessful therapy with all-oral direct-acting antiviral regimens a real-life experience

Milazzo, Lauraa; Magni, Carlob; Niero, Foscab; Schiavini, Monicab; Lai, Alessiaa; Cento, Valeriac; Binda, Francescaa; Antinori, Spinelloa; Sollima, Salvatorea

European Journal of Gastroenterology & Hepatology: November 2017 - Volume 29 - Issue 11 - p 1231–1234
doi: 10.1097/MEG.0000000000000965
Original Articles: Hepatitis

Objective Few real-life data are available on the retreatment of patients who failed direct-acting antiviral (DAA)-regimens. We reported the outcome of retreatment with approved DAA regimens in a real-life cohort of patients who previously failed an all-oral DAAs combination and we analyzed the association with resistance substitutions (RASs) performed at the time of virological failure.

Aim and methods Next-generation sequencing of the NS3, NS5A, and NS5B regions was performed by Illumina deep sequencing. The sequence reads were analyzed by an in-house pipeline.

Results Of the 16/759 (2%) patients who failed to achieve a sustained virological response at 12 weeks to all-oral DAAs from December 2014 to January 2016, 10 were retreated with licensed DAAs regimens. In all the patients, retreatment was followed by sustained virological response at 12 weeks. Baseline NS3-RASs before retreatment were observed in two patients who failed a sofosbuvir/simeprevir regimen: D168V RAS was detected in a genotype-4 patient, whereas the complex RAS-pattern Q80K, I170V, R155K, D168E was observed in a genotype-1a patient. Only one of the two patients who previously failed ombitasvir, paritaprevir/ritonavir, and dasabuvir underwent RAS analysis at relapse and showed baseline NS5A RAS (M28V) before retreatment.

Conclusion These real-life findings indicated a high efficacy of sofosbuvir+NS5A-inihbitors in retreating NS3-experienced patients and also NS5A-experienced patients by using a 24-week course ribavirin-containing regimen. The relevance of hepatitis C virus resistance testing before retreatment remains to be better defined to guide the choice of the new regimen before retreatment in DAA-experienced patients.

aDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan

bFirst Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan

cDepartment of Experimental Medicine and Surgery, University of Rome ‘Tor Vergata’, Rome, Italy

Correspondence to Laura Milazzo, MD, Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy Tel: +39 023 904 3350; fax: +39 025 031 9758; e-mail:

Received March 2, 2017

Accepted May 24, 2017

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.