363
Views
14
CrossRef citations to date
0
Altmetric
Review

An update on direct antiviral agents for the treatment of hepatitis C

, , , , , , , , & show all
Pages 1729-1741 | Received 14 Feb 2021, Accepted 21 Apr 2021, Published online: 11 May 2021

References

  • World Health Organization. Global hepatitis report, 2017. Available from: http://apps.who.int/iris/bitstream/10665/255016/1/9789241565455-eng.pdf?ua=1 Cited 2021 Jan 12
  • AASLD. Recommendations for testing, managing, and treating hepatitis C available online at: https://www.hcvguidelines.org/[Accessed on 2021 Jan 12.
  • Vermehren J, Park JS, Jacobson IM, et al. Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection. J Hepatol. 2018 November;69(5):1178–1187.
  • Stanciu C, Hepatitis TA. C virus treatment revolution: eastern European story. Hepatitis Monthly. 2015 Jul;15(7):e28969.
  • Pawlotsky JM. Interferon-free hepatitis C virus therapy. Cold Spring Harb Perspect Med. 2020 Nov 2;10(11):a036855.
  • Alazard-Dany N, Denolly S, Boson B, et al. Overview of HCV life cycle with a special focus on current and possible future antiviral targets. Viruses. 2019;11(1):30.
  • Dubuisson J, Cosset FL. Virology and cell biology of the hepatitis C virus life cycle: an update. J Hepatol. 2014;61(1):S3–13.
  • Sharma G, Raheja H, Hepatitis DS. C virus: enslavement of host factors: HOST-HCV INTERACTION. IUBMB Life. 2018;70(1):41–49.
  • Chatterji U, Bobardt M, Tai A, et al. Cyclophilin and NS5A inhibitors, but not other anti-hepatitis C virus (HCV) agents, preclude HCV-mediated formation of double-membrane-vesicle viral factories. Antimicrob Agents Chemother. 2015;59(5):2496–2507.
  • Berger KL, Cooper JD, Heaton NS, et al. Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009;106(18):7577–7582.
  • Lavie M, Dubuisson J. Interplay between hepatitis C virus and lipid metabolism during virus entry and assembly. Biochimie 2017;141:62–69.
  • Pan Q, et al. Telaprevir/boceprevir era: from bench to bed and back. World J Gastroenterol. 2012;18(43):6183–6188.
  • Lawitz E, Jacobson IM, Nelson DR. et al., Development of sofosbuvir for the treatment of hepatitis C virus infection. Ann N Y Acad Sci. 1358(1): 56–67. 2015.
  • El Kassas M, Elbaz T, Hafez E, et al. Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection. Expert Opin Drug Discov. 2017;12(6):635–642.
  • European Association for the Study of the Liver. Electronic address: [email protected], Clinical Practice Guidelines Panel. Chair: EASL governing board representative:, panel members: EASL recommendations on treatment of hepatitis C: final update of the series. J Hepatol. 2020;73(5):1170–1218.
  • Chahine EB, Sucher AJ, Hemstreet BA. Sofosbuvir/velpatasvir: the first pangenotypic direct-acting antiviral combination for hepatitis C. Ann Pharmacother. 2017;51(1):44–53.
  • Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373(27):2599–2607.
  • Danvers MA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. AASLD-IDSA. 2017 Cited 2020 Dec 22; Available from: http://hcvguidelines.org/
  • Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376(22):2134–2146.
  • Jacobson IM, Lawitz E, Gane EJ, et al. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology. 2017;153(1):113–122.
  • FDA approves mavyret for hepatitis C. Silver spring, MD: FDA; 2017. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm570038.htm August 3 [2020 Dec 22
  • COMMISSION IMPLEMENTING DECISION granting marketing authorisation under Regulation (EC) No 726/2004 of the European Parliament and of the Council for “Maviret - glecaprevir/pibrentasvir”, a medicinal product for human use. Brussels, Belgium: European commission; 2017. Available from: http://ec.europa.eu/transparency/regdoc/?fuseaction=list&coteId=3&year=2017&number=5428&language=EN July 26 [Cited 2020 Dec 22.
  • Lamb YN. Glecaprevir/pibrentasvir: first global approval. Drugs. 2017;77(16):1797–1804.
  • Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis. J Hepatol. 2017;67(2):263–271.
  • Wyles D, Poordad F, Wang S, et al. Glecaprevir/pibrentasvir for hepatitis C virus genotype 3 patients with cirrhosis and/or prior treatment experience: a partially randomized phase 3 clinical trial. Hepatology. 2017;67(2):514–523.
  • Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2018;16(3):417–426.
  • Zeuzem S, Foster GR, Wang S, et al. Glecaprevir–pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018;378(4):354–369.
  • Forns X, Lee SS, Valdes J, 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, openlabel, multicentre phase 3 trial. Lancet Infect Dis. 2017;17(10):1062–1068.
  • Reau N, Kwo P, Rhee S, et al. MAGELLAN-2: safety and efficacy of glecaprevir/pibrentasvir in liver or renal transplant adults with chronic hepatitis C genotype 1–6 infection. J Hepatol. 2017;66(1):S90–1.
  • A study to evaluate the efficacy and safety of ABT-493/ABT-530 in combination with sofosbuvir and ribavirin in participants with hepatitis C virus who did not respond to treatment in a previous AbbVie clinical study (MAGELLAN-3). Bethesda, MD: NIH; 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02939989 October 20 Cited 2020 Dec 22
  • A study to evaluate the efficacy and safety of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus genotype 1–6 infection and renal impairment (Expedition-5). Bethesda, MD: NIH; 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT03069365?term=expedition5&cond=hcv&rank=1. March 3 Cited 2020 Dec 22
  • World Health Organization. Progress report on access to hepatitis C treatment. focus on overcoming barriers in low and middle income countries, march 2018. geneva, Switzerland: world health organization. (WHO/CDS/HIV/184) Licence: CC BY-NC-SA 30 IGO. 2018;
  • Ven N Van De N, Fortunak J, Simmons B, et al. Minimum target prices for production of direct acting antivirals and associated diagnostics to combat hepatitis C virus. Hepatology. 2015;61(4):1174–1182.
  • Emmanuel B, Wilson EM, O’Brien TR, et al. Shortening the duration of therapy for chronic hepatitis C infection. Lancet Gastroenterol Hepatol. 2017;2(11):832–836.
  • Lim JK. Management of hepatitis C in special populations:HIV coinfection, renal disease, and decompensated cirrhosis. Clin Liver Dis. 2020;16(1):29–31.
  • Pol S, Parlati L. Treatment of hepatitis C: the use of the new pangenotypic direct-acting antivirals in “special populations. Liver International. 2018;38((Suppl1)): 28–33.
  • Ghany MG, Morgan TR. AASLD-IDSA hepatitis C guidance panel. hepatitis C guidance 2019 update: American association for the study of liver diseases-infectious diseases society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020;71(2):686–721.
  • Schlabe S, Rockstroh JK. Advances in the treatment of HIV/HCV coinfection in adults. Expert Opin Pharmacother. 2018;19(1):49–64.
  • Pol S, Parlati L, Jadoul M. Hepatitis C virus and the kidney. Nat Rev Nephrol. 2019;15(2):73–86.
  • Susanna N, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1 for the ION-4 investigators. N Engl J Med. 2015;373(8):705–713.
  • Osinusi A, Townsend K, Anita K, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV Co-infection. JAMA. 2015;313(12):1232–1239.
  • Perillo RP. Hepatitis B virus reactivation during direct-acting antiviral treatment of chronic hepatitis C: a hidden danger of an otherwise major success story. Hepatology. 2017;66:4‐6.
  • Gilead Sciences. Harvoni (ledipasvir/sofosbuvir) [package insert]. Foster City, CA: Gilead Sciences; 2019.
  • Gilead Sciences. Sovaldi (sofosbuvir) [package insert]. Foster City, CA: Gilead Sciences; 2019.
  • AbbVie. Mavyret (glecaprevir/pibrentasvir) [package insert]. North Chicago, IL: AbbVie; 2019.
  • Indolfi G, Fischler B, Gonzalez-Peralta RP, et al., Comparison of recommendations for treatment of chronic hepatitis C virus infection in children and adolescents: a position paper of the federation of international societies of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 70(5): 711–717. 2020.
  • Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149(3):649–659.
  • Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016;16(6):685–697.
  • Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373(27):2618–2628.
  • Flamm S, Lawitz E, Borg B, et al. THU-138-high efficacy and improvement in CPT class with sofosbuvir/velpatasvir plus ribavirin for 12 weeks in patients with CPT C decompensated cirrhosis. J Hepatol. 2019;70(1):e221–2.
  • El-Sherif O, Jiang ZG, Tapper EB, et al. Baseline factors associated with improvements in decompensated cirrhosis after direct-acting antiviral therapy for hepatitis C virus infection. Gastroenterology. 2018;154(8):2111–2121.e8.
  • Van Der Meer AJ, Berenguer M. Reversion of disease manifestations after HCV eradication. J Hepatol. 2016;65(1):S95–108.
  • Young K, Liu B, Bhuket T, et al. Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct-acting antiviral therapies in the United States. J Viral Hepat. 2019;26(3):350–361.
  • Kwong A, Kim WR, Mannalithara A, et al. Decreasing mortality and disease severity in hepatitis C patients awaiting liver transplantation in the United States. Liver Transpl. 2018;24(6):735–743.
  • Crespo G, Trota N, Londoño MC, et al. The efficacy of direct anti-HCV drugs improves early post-liver transplant survival and induces significant changes in waiting list composition. J Hepatol. 2018;69(1):11–17.
  • Belli LS, Perricone G, Adam R, et al. Impact of DAAs on liver transplantation: major effects on the evolution of indications and results. An ELITA study based on the ELTR registry. J Hepatol. 2018;69(4):810–817.
  • Chhatwal J, Samur S, Kues B, et al. Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list. Hepatology Baltim Md. 2017;65(3):777–788.
  • Cortesi PA, Belli LS, Facchetti R, et al. The optimal timing of hepatitis C therapy in liver transplant-eligible patients: cost-effectiveness analysis of new opportunities. J Viral Hepat. 2018;25(7):791–801.
  • Agarwal K, Castells L, Müllhaupt B, et al. Sofosbuvir/velpatasvir for 12 weeks in genotype 1–4 HCV-infected liver transplant recipients. J Hepatol. 2018;69(3):603–607.
  • He S, Lockart I, Alavi M, et al. Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma. Aliment Pharmacol Ther. 2020;51(1):34–52.
  • Beste LA, Green PK, Berry K, et al. Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J Hepatol. 2017;67(1):32–39.
  • Prenner SB, VanWagner LB, Flamm SL, et al. Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals. J Hepatol. 2017;66(6):1173–1181.
  • Sachdeva MChawla YK, Arora SK Immunology of hepatocellular carcinoma. World J Hepatol. 2015;7(17):2080–2090.
  • Konjeti VR, John BV. Interaction between hepatocellular carcinoma and hepatitis C eradication with direct-acting antiviral therapy. Curr Treat Options Gastroenterol. 2018;16(2):203–214.
  • Chung RT, Ghany MG, Kim AY, Hepatitis C guidance 2018. update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67(10):1477–1492.
  • Soria ME, García-Crespo C, Martínez-González B, et al. Amino acid substitutions associated with treatment failure for hepatitis C virus infection. J Clin Microbiol. 2020;58(12):e01985–20.
  • Esposito I, Trinks J, Hepatitis SV. C virus resistance to the new direct-acting antivirals. Expert Opin Drug Metab Toxicol. 2016;12(10):1197–1209.
  • Itakura J, Kurosaki M, Hasebe C, et al. Complex pattern of resistance-associated substitutions of hepatitis C virus after daclatasvir/asunaprevir treatment failure. PLoS One. 2016;11(10):e0165339. .
  • Zeuzem S, Mizokami M, Pianko S, et al. NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: prevalence and effect on treatment outcome. J Hepatol. 2017;66(5):910–918.
  • Uchida Y, Nakamura S, Kouyama J-I, et al. Significance of NS5B substitutions in genotype 1b hepatitis C virus evaluated by bioinformatics analysis. Scientific Reports. 2018;8(1):8818.
  • Krishnan P, Schnell G, Tripathi R, et al. Analysis of hepatitis C virus genotype 1b resistance variants in Japanese patients treated with paritaprevir-ritonavir and ombitasvir. Antimicrob Agents Chemother. 2015;60(2):1106–1113.
  • Zeuzem S, Serfaty L, Vierling J, et al. The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection. J Gastroenterol. 2018;53(5):679–688.
  • McPhee F, Hernandez D, Zhou N, et al. Pooled analysis of HCV genotype 1 resistance-associated substitutions in NS5A, NS3 and NS5B pre-and post-treatment with 12 weeks of daclatasvir, asunaprevir and beclabuvir. Antivir Ther. 2018;23(1):53–66.
  • Teraoka Y, Uchida T, Imamura M, et al. Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure. J Gen Virol. 2018;99(8):1058–1065.
  • Dietz J, Susser S, Vermehren J, et al. European HCV resistance study group. patterns of resistance associated substitutions in patients with chronic HCV infection following treatment with direct-acting antivirals. Gastroenterology. 2018;154(4):976–988.
  • Harrington PR, Komatsu TE, Deming DJ, et al. Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: regulatory analyses and perspectives. Hepatology. 2018;67(6):2430–2448.
  • Bhatia M, Gupta E. Emerging resistance to directly-acting antiviral therapy in treatment of chronic hepatitis C infection-A brief review of literature. J Family Med Prim Care. 2020;9(2):531–538.
  • Arias A, Aguilera A, Soriano V, et al. Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials. Antivir Ther. 2017;22(4):307–312.
  • Alimirah M, Sadiq O, Gordon SC. Management of direct-acting antiviral failures. Clin Liver Dis (Hoboken). 2020;16(1):25–28.
  • Schulte B, Wübbolding M, Marra F, et al., Frequency of potential drug-drug interactions in the changing field of HCV therapy. Open Forum Infect Dis. 7(2): ofaa040. 2020.
  • Kuo MH, Tseng CW, Lee CH, et al. Drug-drug interactions between direct-acting antivirals and statins in the treatment of chronic hepatitis C. Tzu Chi Med J. 2020;32(4):331–338.
  • Lexi-Comp. Drug-drug interaction. Riverwoods, IL: Lexicomp, Wolters Kluwer Health, Inc; 2019.
  • Liverpool Uo. University of liverpool hepatitis drug interactions website. Available from: https://www.hep-druginteractions.org/. Last accessed on 2021 Jan 6
  • Smolders EJ, Jansen AM, Ter Horst PG, et al. Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations: a 2019 update. Clin Pharmacokinet. 2019;58(10):1237–1263.
  • Bichmann L, Wang YT, Fischer WB. Docking assay of small molecule antivirals to p7 of HCV. Comput Biol Chem. 2014;53:308–317.
  • Luscombe CA, Huang Z, Murray MG, et al. A novel hepatitis C virus p7 ion channel inhibitor, BIT225, inhibits bovine viral diarrhea virus in vitro and shows synergism with recombinant interferon-alpha-2b and nucleoside analogues. Antiviral Res. 2010;86(2):144–153.
  • Pavlovic D, Fischer W, Hussey M, et al. Long alkylchain iminosugars block the HCV p7 ion channel. Adv Exp Med Biol. 2005;564:3–4.
  • Mailly L, Xiao F, Lupberger J, et al. Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nat Biotechnol. 2015;66(5):910–918.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.