Year 2016 / Volume 108 / Number 7
Review
Causes of treatment failure for hepatitis C in the era of direct-acting antiviral therapy

421-430

DOI: 10.17235/reed.2015.3894/2015

Joaquín Cabezas, Susana Llerena, Ángela Puente, Emilio Fábrega, Javier Crespo,

Abstract
Hepatitis C therapy in the era of the newer direct-acting antiviral agents has radically changed our treatment schemes by achieving very high rates of sustained virological response. However, treatment with direct antiviral agents fails in a subgroup of patients. This group of so-called difficult-to-treat individuals is the subject of this paper, which reviews the causes of virological failure, their clinical implications, and some final recommendations.
Share Button
New comment
Comments
No comments for this article
References
1. Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;2444:359-62.
2. Plan Estrategico Nacional frente al VHC 2015 [17/06/2015]. Available from: http://aeeh.es/wp-content/uploads/2015/04/a77478e2a1147600cb9979b5992281cb.pdf.
3. Jensen DM, et al. Safety and efficacy of sofosbuvir-containing regimens for hepatitis C: Real-World experience in a diverse, longitudinal observational cohort. 65th Annual Meeting of the AASLD. 2014;Abstract 45.Hepatology. 2014; 60 (Supp 4):219A
4. Terrault N. Difficult-to-Cure populations with chronic hepatitis C: Vanishing in the DAA era? Hepatology. 2015;62:4-7 DOI: 10.1002/hep.27892
5. Nelson DR, Cooper JN, Lalezari, JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61:1127-35.
6. Foster GR, Pianko S, Cooper C, et al. Sofosbuvir + Peginterferon/Ribavirin for 12 weeks vs Sofosbuvir + Ribavirin for 16 or 24 weeks in genotype 3 HCV infected patients and treatment-experienced cirrhotic patients with genotype 2 HCV: The BOSON study. J Hepatol 2015;62(Supp2):S259.
7. Saxena V NL, Pauly M, et al. . Safety and Efficacy of Simeprevir/Sofosbuvir in Hepatitis C Infected Patients with Compensated and Decompensated Cirrhosis: A Matched Analysis. J Hepatol. 2015;62 (Supp 2):S669-S70.
8. Smith DB, Bukh J, Kuiken C, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59:318-27.
9. Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology. 2014;146:1176-92.
10. Benedet M, Adachi D, Wong A, et al. . The need for a sequencing-based assay to supplement the Abbott m2000 RealTime HCV Genotype II assay: a 1 year analysis. J Clin Virol. 2014;60:301-4.
11. Quer J, Gregori, J, Rodriguez-Frias F, et al. High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods. J Clin Microbiol. 2015;53:219-26.
12. Ceccherini Silberstein F, Di Maio VC, Aragri M, et al. Hepatitis C Virus Gene Sequencing as a Tool for Precise Genotyping in the Era of New Direct Antiviral Agents. Hepatology. 2015.In press.
13. Liu CH, Liang CC, Liu, CJ, et al. Comparison of Abbott RealTime HCV Genotype II with Versant Line Probe Assay 2.0 for Hepatitis C Virus Genotyping. J Clin Microbiol. 2015;53:1754-7.
14. Morel V, Fournier C, Francois C, et al. Genetic recombination of the hepatitis C virus: clinical implications. J Viral Hepat. 2011;18:77-83.
15. Hedskog C, Doehle B, Chodavarapu K, et al. Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin. Hepatology. 2015;61:471-80.
16. Sarrazin C, Kieffer TL, Bartels D, et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology. 2007;132:1767-77.
17. Wyles DL, Gutierrez JA. Importance of HCV genotype 1 subtypes for drug resistance and response to therapy. J Viral Hepat.. 2014;21:229-40. DOI: 10.1111/jvh.12230
18. Bartels DJ, Zhou Y, Zhang EZ, et al. Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3.4A protease inhibitors in treatment-naive subjects. J Infect Dis. 2008;198:800-7.
19. Cabezas J, Menéndez S, Puente A, et al. Polimorfismos del Q80K en un región del Norte de España. Gastroenterol Hepatol. 2015;38.
20. Wang C, Sun JH, O'Boyle DR, et al. Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir. Antimicrob Agents Chemother. 2013;57:2054-65.
21. Svarovskaia ES, Dvory-Sobol H, Parkin N, et al. Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. Clin Infect Dis. 2014;59:1666-74.
22. Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368:34-44.
23. Zeuzem S, Buggisch P, Agarwal K, et al. The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C. Hepatology. 2012;55:749-58.
24. Bartels DJ, Sullivan JC, Zhang EZ, et al. Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment. J Virol. 2013;87:1544-53.
25. Donaldson EF, Harrington PR, O'Rear JJ, Naeger LK. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology. 2015;61:56-65.
26. Pawlotsky JM. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology. 2011;53:1742-51.
27. Pawlotsky JM. Is hepatitis virus resistance to antiviral drugs a threat? Gastroenterology. 2012;142:1369-72. DOI: 10.1053/j.gastro.2011.12.060
28. Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology. 2010;138:447-62.
29. Farnik H, Vermehren J, Susser S, et al. Epidemiology of viral resistance in genotype 1 infected patients at approval of IFN-free DAA combination therapy of chronic hepatitis C in Germany. J Hepatol. 2015;62:S616.
30. Cook J, Solberg O, Newton A, et al. Characterization of Naturally Occurring Resistance to HCV NS5A Inhibitors. [CROI Abstract 696] Conference on Retroviruses and Opportunistic Infections. Top Antivir Med 2015;23(e-1):307.
31. Dvory-Sobol HWD, Ouyang W, et al. Long-term persistence of HCV NS5A variants after treatment with NS5Ainhibitor Ledipasvir. J Hepatol 2015;62(Supp 2):S221.
32. Black S, Pak I, Ingravallo P, et al. Resistence analysis of virologic failures in Hepatitis C genotype 1 infected patients treated with Grazoprevir/Elbasvir +/- Ribavirin: The C-Worthy study. J Hepatol 2015;62(Supp 2):S677
33. Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. The prevalence and the effect of HCV NS5A resistence associated variants in subjects with compensated cirrhosis treated with Ledipasvir/Sofosbuvir +/- RBV. J Hepatol 2015;62 (Supp 2):S620
34. Lawitz E, Flamm S, Yang JC, et al. Retreatment of patients who failed 8 or 12 weeks of Ledipasvir/Sofosbuvir- based regimens with Ledipasvir/Sofosbuvir for 24 weeks. J Hepatol. 2015;62 (Supp 2):S192.
35. Fevery B, Thys K, Van Eygen V, et al. Deep Sequencing Analyses of minority baseline polymorphisms and persistence of emerging mutations in HCV senotype 1 infected patients treated with Simeprevir. J Hepatol. 2014;60:S139.
36. Krishnan PTR, Schnell G, et al. Long-term follow-up of treatment-emergent resistence-associated variants in NS3, NS5A and NS5B with Paritaprevir/R-, Ombitasvir-, and Dasabuvir-based regimens. J Hepatol. 2015;62 (Supp 2):S220.
37. Dietz J, Berkowski C, Perner D, et al.Consideration of viral resistence for optimization of direct antiviral therapy of Chronic Hepatitis C. J Hepatol. 2015;62 (Supp 2):S681.
38. AASLD. Recommendations for Testing, Managing, and Treating Hepatitis C 2015 [17/06/2015]. Available from: http://www.hcvguidelines.org/full-report-view.
39. EASL. Recommendations on treatment of Hepatitis C 2015 2015 [17/06/2015]. Available from: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines/detail/recommendations-on-treatment-of-hepatitis-c-2015.
40. AEEH. Documento del II Consenso español sobre tratamiento de la hepatitis C 2015 [17/06/2015]. Available from: http://aeeh.es/wp-content/uploads/2015/04/II-Conferencia-de-consenso-sobre-el-tratamiento-de-la-hepatitis-C-de-la-AEEH.pdf.
41. Serpaggi J, Chaix ML, Batisse D, et al. Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy. Aids. 2006;20:233-40.
42. Thomson EC, Main J. Epidemiology of hepatitis C virus infection in HIV-infected individuals. J Viral Hepat. 2008;15:773-81.
43. Grebely J, Pham ST, Matthews GV, et al. Hepatitis C virus reinfection and superinfection among treated and untreated participants with recent infection. Hepatology. 2012;55:1058-69.
44. Simmons B, Saleem, J, Heath K, et al. Long-term treatment outcomes of patients infected with Hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a Sustained Virological Response. Clin Infect Dis. 2015; 61:730-40.
45. Abdelrahman T, Hughes J, Main J, et al. Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment. Hepatology. 2015;61:88-97.
46. Pham ST, Bull RA, Bennett JM, et al. Frequent multiple hepatitis C virus infections among injection drug users in a prison setting. Hepatology. 2010;52:1564-72.
47. Forton DM, Karayiannis P, Mahmud N, et al. Identification of unique hepatitis C virus quasispecies in the central nervous system and comparative analysis of internal translational efficiency of brain, liver, and serum variants. J Virol. 2004;78:5170-83.
48. McNaughton AL, Thomson EC, Templeton K, et al. Mixed genotype hepatitis C infections and implications for treatment. Hepatology. 2014;59:1209.
49. Soriano V, Vispo E, de Mendoza C, et al. Very late relapse after discontinuation of antiviral therapy for chronic hepatitis C. Antivir Ther. 2013;18:1033-5.
50. Svarovskaia E, Martin R, Chodavarapu Chodavarapu K, Hedskog Hedskog C, Brainard D, Miller MD, et al. HCV reinfection in phase 3 studies of sofosbuvir. J Hepatol. 2015;62 (Supp 2):S222-S3.
51. Wang C, Sun JH, O'Boyle DR, Nower P, Valera L, Roberts S, et al. Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir. Antivir Ther. 2013;57:2054-65.
52. Krishnan P, Tripathi R, Schnell G, et al. Pooled analysis of resistance in patients treated with ombitasvir/ABT-450/r and dasabuvir with or without ribavirin in Phase 2 and Phase 3 clinical trials. Hepatology. 2014;60:1134A.
53. Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. Baseline and post-baseline resistance analyses of Phase 2/3 studies of ledipasvir/sofosbuvir RBV. Hepatology. 2014;60:1128A.
Related articles

Editorial

Cases of liver disease lost in the health system: a call to action

DOI: 10.17235/reed.2021.8316/2021

Original

Active search for hepatitis C patients in primary care

DOI: 10.17235/reed.2021.8067/2021

Original

Hepatitis C in homeless people: reaching a hard-to-reach population

DOI: 10.17235/reed.2021.7737/2020

Editorial

Screening guide for hepatitis C virus infection in Spain

DOI: 10.17235/reed.2020.7728/2020

Special Article

Strategy for the Elimination of Hepatitis C in Cantabria

DOI: 10.17235/reed.2020.7108/2020

Editorial

Reflex testing. A key tool for the elimination of hepatitis C

DOI: 10.17235/reed.2020.7201/2020

Original

Quality of life study in asymptomatic patients with hepatitis C

DOI: 10.17235/reed.2019.6339/2019

Letter

Acute seronegative hepatitis C: two case reports

DOI: 10.17235/reed.2019.5921/2018

Citation tools
Cabezas J, Llerena S, Puente Á, Fábrega E, Crespo J. Causes of treatment failure for hepatitis C in the era of direct-acting antiviral therapy . 3894/2015


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 1167 visits.
This article has been downloaded 236 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 17/06/2015

Accepted: 21/09/2015

Online First: 15/12/2015

Published: 11/07/2016

Article revision time: 91 days

Article Online First time: 181 days

Article editing time: 390 days


Share
This article hasn't been rated yet.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology