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Treatment of DAA-Experienced Patients with Chronic Hepatitis C

  • Hepatitis C (A Aronsohn and H Vargas, Section Editors)
  • Published:
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Abstract

Purpose of Review

The development of interferon-free direct-acting antiviral (DAA) regimens for the treatment of chronic hepatitis C (HCV) has significantly improved rates of sustained virologic response (SVR), shortened treatment duration, and improved drug tolerability across genotypes. While SVR rates now exceed 95% among treatment-naïve patients, there are a growing number of patients who have experienced DAA treatment failure and represent an emerging clinical challenge. This review discusses recent data on sofosbuvir/velpatasvir/voxilaprevir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir for the treatment of DAA-experienced patients, as well as updated American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines.

Recent Findings

Data from phase 3 randomized clinical trials show that retreatment of DAA failures is successful in > 90% of patients using the above three regimens. The preferred retreatment regimen is dependent on HCV genotype, possible drug-drug interactions, prior treatment experience, and host factors such as the presence of cirrhosis and renal failure. Sofosbuvir/velpatasvir is a reasonable option for DAA-experienced genotype 1b and genotype 2 patients, but has been shown to be inferior to sofosbuvir/velpatasvir/voxilaprevir in genotype 1a and genotype 3 patients. Glecaprevir/pibrentasvir is a very attractive option for treatment of DAA-experienced genotype 1 and 2 patients, but it is not approved for treatment of DAA-experienced patients with genotype 3, and data is lacking to support its use in DAA treatment-experienced patients with genotypes 4–6.

Summary

The potency and high barrier to resistance of newer DAA regimens create an opportunity to cure most people with chronic hepatitis C, regardless of prior treatment failures. It is now possible to consider elimination of hepatitis C; the remaining barriers are the cost of therapy and access to care.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Naggie S, Muir AJ. Oral combination therapies for hepatitis C virus infection: successes, challenges, and unmet needs. Annu Rev Med. 2017;68:345–58.

    Article  CAS  PubMed  Google Scholar 

  2. Wyles D, Mangia A, Cheng W, Shafran S, Schwabe C, Ouyang W, et al. Long-term persistence of HCV NS5A resistance associated substitutions after treatment with the HCV NS5A inhibitor, ledipasvir, without sofosbuvir. Antivir Ther. 2017;

  3. Sarrazin C, Dvory-Sobol H, Svarovskaia ES, Doehle BP, Pang PS, Chuang SM, et al. Prevalence of resistance-associated substitutions in HCV NS5A, NS5B, or NS3 and outcomes of treatment with ledipasvir and sofosbuvir. Gastroenterology. 2016;151:501–12.

    Article  CAS  PubMed  Google Scholar 

  4. •• AASLD/IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. https://www.hcvguidelines.org. Consensus guidelines on the retreatment of hepatitis C, with a review of recent pivotal studies.

  5. Kim, A. 2017 IDWeek abstract 943 Management of first line HCV treatment failures, Oct 6, 2017. San Diego, CA.

  6. Anderson JC, Simonetti J, Fisher DG, Williams J, Yamamura Y, Rodriguez N, et al. Comparsion of different HCV viral load and genotyping assays. J Clin Virol. 2003;28:27–37.

    Article  CAS  PubMed  Google Scholar 

  7. Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142:1293–302.

    Article  PubMed  Google Scholar 

  8. Kohli A, Kattakuzhy S, Sidharthan S, Nelson A, McLaughlin M, Seamon C, et al. Four-week direct-acting antiviral regimens in noncirrhotic patients with hepatitis C virus genotype 1 infection: an open-label, nonrandomized trial. Ann Intern Med. 2015;163:899–907.

    Article  PubMed  Google Scholar 

  9. Brown A, et al. Adherence to pangenotypic glecaprevir/pibrentasvir treatment and SVR12 in HCV-infected patients: an integrated analysis of the phase 2/3 clinical trial program. Abstract 198. AASLD 2017, Washington.

  10. Terrault NA, Zeuzem S, di Bisceglie AM, Lim JK, Pockros PJ, Frazier LM, et al. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated of sustained virologic response. Gastroenterology. 2016;151(6):1131–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sarrazin C, Isakov V, Svarovskaia ES, Hedskog C, Martin R, Chodavarapu K, et al. Late relapse versus hepatitis C virus reinfection in patients with sustained virologic response after sofosbuvir-based therapies. Clin Infect Dis. 2017;64(1):44–52.

    Article  PubMed  Google Scholar 

  12. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61:77–87.

    Article  PubMed  Google Scholar 

  13. •• Bourliere M, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376:2134–46. The largest and most comprehensive phase 3 study of DAAs for prior DAA failures.

    Article  CAS  PubMed  Google Scholar 

  14. Spach, DH, Kim HN. Treatment of HCV genotype 1. Hepatitis C Online Updated November 15, 2017. https://www.hepatitisc.uw.edu/browse/all/core-concepts.

  15. • Poordad F, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 66(2):389–97. Phase 3 study of glecaprevir and pibrentasvir in prior DAA failures.

  16. Poordad F, et al. MAGELLAN-1, part 2: glecaprevir and pibrentasvir for 12 or 16 weeks in patients with chronic hepatitis C virus genotype 1 or 4 and prior direct-acting antiviral treatment failure. J Hepatol. 66(1):S83–4.

  17. Zeuzem S, Feld J, Wang S. ENDURANCE-1: efficacy and safety of 8- versus 12-week treatment with ABT-493/ABT-530 in patients with chronic HCV genotype 1 infection [Abstract 253]. In 67th Annual Meeting of the American Association for the Study of Liver diseases, November 11–15. 2016.

  18. Forns X, Lee SS, Valdes J, Lens S, Ghalib R, Aguilar H, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5 or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicenter phase 3 trial. Lancet Infect Dis. 2017;17:1062–8.

    Article  CAS  PubMed  Google Scholar 

  19. Osinusi A, et al. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse. Annals Int Med 20014. 2014;161:634–8.

    Article  Google Scholar 

  20. Wyles D, Pockros P, Morelli G, Younes Z, Svarovskaia E, Yang JC, et al. Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens. Hepatology. 2015;61:1793–7.

    Article  CAS  PubMed  Google Scholar 

  21. Spach DH, Kim HN. Treatment of HCV genotype 2. Hepatitis C Online. 2016. https://www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-2/core-concept/all.

  22. Asselah T, Kowdley KV, Zadeikis N, Wang S, Hassanein T, Horsmans Y, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2017;16:417–26. https://doi.org/10.1016/j.cgh.2017.09.027.

    Article  PubMed  Google Scholar 

  23. Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS Jr, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149(3):649–59.

    Article  CAS  PubMed  Google Scholar 

  24. • Wyles D, et al. Hepatology. 2017; https://doi.org/10.1002/hep.29541. A smaller study that only examined patients who had failed sofosbuvir.

  25. Hepatitis C Online. Hepatitis C treatments https://www.hepatitisc.uw.edu/page/treatment/drugs/glecaprevir-pibrentasvir/drug-summary.

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Authors and Affiliations

  1. Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA

    Maria A. Corcorran & John D. Scott

  2. Harborview Medical Center, 325 Ninth Ave, Box 359938, Seattle, WA, 98104, USA

    John D. Scott

Authors
  1. Maria A. Corcorran
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  2. John D. Scott
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Correspondence to John D. Scott.

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Conflict of Interest

Maria A. Corcorran declares no conflicts of interest.

John D. Scott reports personal fees from Novartis, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Hepatitis C

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Corcorran, M.A., Scott, J.D. Treatment of DAA-Experienced Patients with Chronic Hepatitis C. Curr Hepatology Rep 17, 121–129 (2018). https://doi.org/10.1007/s11901-018-0395-9

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