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Virology Journal
Published in: Virology Journal 1/2018

Open Access 01-12-2018 | Review

Treatment of hepatitis C virus genotype 4 in the DAA era

Authors: Antonio Di Biagio, Lucia Taramasso, Giovanni Cenderello

Published in: Virology Journal | Issue 1/2018

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Abstract

The recently approved interferon-free DAA (direct antiviral agents) regimens have shown not only to be effective in terms of sustained virological response (SVR) rates (> 90%) but also well tolerated in most hepatitis C virus (HCV) infected patients. Nevertheless HCV genotypes are different and only a small percentage of trials consider genotype 4 (GT4), which was associated with lower rates of SVR compared with other genotypes before the arrival of the DAA’s. In this review, we discuss the efficacy of DAA therapy in GT4 HCV infection with specific reference to more recent studies, including those conducted in a ‘field-practice’ scenario. Overall, DAA-based regimens appear more effective also in the poorly-explored setting of patients with HCV GT4 infection. Despite an overall limited number of patients was evaluated, favorable results are being derived from studies on ombitasvir/paritaprevir/ritonavir, sofosbuvir and velpatasvir, whether or not in association with voxilaprevir, and with the new combined therapy glecaprevir + pibentasvir.
Literature
1.
Arias A, Aguilera A, Soriano V, Benítez-Gutiérrez L, Lledó G, Navarro D, Treviño A, Otero E, Peña JM, Cuervas-Mons V, de Mendoza C. Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials. Antivir Ther. 2017;22:307–12.CrossRef
2.
Arends JE, Kracht PA, Hoepelman AI. European study Group for Viral Hepatitis (ESGVH)2. Performance of hepatitis C virus (HCV) direct-acting antivirals in clinical trials and daily practice. Clin Microbiol Infect. 2016;22:846–52.CrossRef
3.
Majumdar A, Kitson MT, Roberts SK. Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis. Aliment Pharmacol Ther. 2016;43:1276–92.CrossRef
4.
Hathorn E, Elsharkawy AM. Management of hepatitis C genotype 4 in the directly acting antivirals era. BMJ Open Gastroenterol. 2016;3:e000112.CrossRef
5.
Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61(Suppl 1):45–57.CrossRef
6.
Abd Elrazek AE, Bilasy SE, Elbanna AE, Elsherif AE. Prior to the oral therapy, what do we know about HCV-4 in Egypt: a randomized survey of prevalence and risks using data mining computed analysis. Medicine (Baltimore). 2014;93:e204.CrossRef
7.
D'Arminio Monforte A, Cozzi-Lepri A, Ceccherini-Silberstein F, De Luca A, Lo Caputo S, Castagna A, Mussini C, Cingolani A, Tavelli A, Shanyinde M, Gori A, Girardi E, Andreoni M, Antinori A. Puoti M; Icona Foundation and HepaIcona Study Group. Access and response to direct antiviral agents (DAA) in HIV-HCV co-infected patients in Italy: Data from the Icona cohort. PLoS One. 2017;12:e0177402.CrossRef
8.
Ruane PJ, Ain D, Stryker R, Meshrekey R, Soliman M, Wolfe PR, et al. Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestry. J of Hepatology. 2015;62:1040–6.CrossRef
9.
Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, JG MH, Agarwal K, Zeuzem S. ASTRAL-1 investigators. Sofosbuvir and Velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599–607.CrossRef
10.
Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M. ASTRAL-4 investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015;373:2618–28.CrossRef
11.
Gane EJ, Kowdley KV, Pound D, Stedman CA, Davis M, Etzkorn K, Gordon SC, Bernstein D, Everson G, Rodriguez-Torres M, Tsai N, Khalid O, Yang JC, Lu S, Dvory-Sobol H, Stamm LM, Brainard DM, McHutchison JG, Tong M, Chung RT, Beavers K, Poulos JE, Kwo PY, Nguyen MH. Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in patients with hepatitis C virus genotype 2, 3, 4, or 6 infections in an open-label, phase 2 trial. Gastroenterology. 2016;151:902–9.CrossRef
12.
Bourlière M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, Ravendhran N, Vierling JM, Tran TT, Pianko S, Bansal MB, de Lédinghen V, Hyland RH, Stamm LM, Dvory-Sobol H, Svarovskaia E, Zhang J, Huang KC, Subramanian GM, Brainard DM, McHutchison JG, Verna EC, Buggisch P, Landis CS, Younes ZH, Curry MP, Strasser SI, Schiff ER, Reddy KR, Manns MP, Kowdley KV, Zeuzem S. POLARIS-1 and POLARIS-4 Investigators. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017;376:2134–46.CrossRef
13.
Colombo M, Aghemo A, Liu H, Zhang J, Dvory-Sobol H, Hyland R, Yun C, Massetto B, Brainard DM, McHutchison JG, Bourlière M, Peck-Radosavljevic M, Manns M, Pol S. Treatment with Ledipasvir-Sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection: a randomized trial. Ann Intern Med. 2017;166:109–17.CrossRef
14.
Kohli A, Kapoor R, Sims Z, Nelson A, Sidharthan S, Lam B, Silk R, Kotb C, Gross C, Teferi G, Sugarman K, Pang PS, Osinusi A, Polis MA, Rustgi V, Masur H, Kottilil S. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-Centre, open-label phase 2a cohort study. Lancet Infect Dis. 2015;15:1049–54.CrossRef
15.
Buti M, Calleja JL, Lens S, Diago M, Ortega E, Crespo J, Planas R, Romero-Gómez M, Rodríguez FG, Pascasio JM, Fevery B, Kurland D, Corbett C, Kalmeijer R, Jessner W. Simeprevir in combination with sofosbuvir in treatment-naïve and –experienced patients with hepatitis C virus genotype 4 infection: a phase III, open-label, single-arm study (PLUTO). Aliment Pharmacol Ther. 2017;45:468–75.CrossRef
16.
El Raziky M, Gamil M, Ashour MK, Sameea EA, Doss W, Hamada Y, Van Dooren G, DeMasi R, Keim S, Lonjon-Domanec I, Hammad R, Hashim MS, Hassany M, Waked I. Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naïve and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis. J Viral Hepat. 2017;24:102–10.CrossRef
17.
Kwo P, Gane EJ, Peng CY, Pearlman B, Vierling JM, Serfaty L, Buti M, Shafran S, Stryszak P, Lin L, Gress J, Black S, Dutko FJ, Robertson M, Wahl J, Lupinacci L, Barr E, Haber B. Effectiveness of Elbasvir and Grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Gastroenterology. 2017;152:164–75.CrossRef
18.
Hézode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, Marcellin P, Hall C, Schnell G, Pilot-Matias T, Mobashery N, Redman R, Vilchez RA, Pol S. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet. 2015;385:2502–9.CrossRef
19.
Waked I, Shiha G, Qaqish RB, Esmat G, Yosry A, et al. Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATHE-II): a multicentre, phase 3, partly randomised open label trial. Lancet Gastroenterol Hepatol. 2016;1:36–44.CrossRef
20.
Hézode Forns X, Lee SS, Valdes J, Lens S, Ghalib R, Aguilar H, Felizarta F, Hassanein T, Hinrichsen H, Rincon D, Morillas R, Zeuzem S, Horsmans Y, Nelson DR, Yu Y, Krishnan P, Lin CW, Kort JJ, Mensa FJ. 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, multicentre phase 3 trial. Lancet Infect Dis. 2017;17:1062–8.CrossRef
21.
Asselah T, Kowdley KV, Zadeikis N, Wang S, Hassanein T, Horsmans Y, Colombo M, Calinas F, Aguilar H, de Ledinghen V, Mantry PS, Hezode C, Marinho RT, Agarwal K, Nevens F, Elkhashab M, Kort J, Liu R, Ng TI, Krishnan P, Lin CW, Mensa FJ. 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. 2017. https://​doi.​org/​10.​1016/​j.​cgh.​2017.​09.​027 [Epub ahead of print].CrossRef
22.
Yakoot M, Abdo AM, Abdel-Rehim S, Helmy S. Response tailored protocol versus the fixed 12 weeks course of dual Sofosbuvir/Daclatasvir treatment in Egyptian patients with chronic hepatitis C Genotype-4 infection: a randomized, open-label. Non-inferiorityTrial EBioMedicine. 2017;21:182–7.CrossRef
23.
El-Khayat H, Fouad Y, Mohamed HI, El-Amin H, Kamal EM, Maher M, Risk A. Sofosbuvir plus daclatasvir with or without ribavirin in 551 patients with hepatitis C-related cirrhosis, genotype 4. Aliment Pharmacol Ther. 2018;47:674–9.CrossRef
24.
Willemse SB, Baak LC, Kuiken SD, van der Sluys VA, Lettinga KD, van der Meer JT, Depla AC, Tuynman H, van Nieuwkerk CM, Schinkel CJ, Kwa D, Reesink HW, van der Valk M. Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life. J Viral Hepat. 2016;23:950–4.CrossRef
25.
Degré D, Sersté T, Lasser L, Delwaide J, Starkel P, Laleman W, Langlet P, Reynaert H, Bourgeois S, Vanwolleghem T, Negrin Dastis S, Gustot T, Geerts A, Van Steenkiste C, de Galocsy C, Lepida A, Orlent H, Moreno C. Sofosbuvir in combination with Simeprevir +/− ribavirin in genotype 4 hepatitis C patients with advanced fibrosis or cirrhosis: a real-world experience from Belgium. PLoS One. 2017;12:e0170933.CrossRef
26.
Asselah T, Moreno C, Sarrazin C, Gschwantler M, Foster GR, Craxí A, Buggisch P, Sanai F, Bicer C, Lenz O, Van Dooren G, Nalpas C, Lonjon-Domanec I, Schlag M, Buti M. Efficacy of a 12-week Simeprevir plus Peginterferon/ribavirin (PR) regimen in treatment-Naïve patients with hepatitis C virus (HCV) genotype 4 (GT4) infection and mild-to-moderate fibrosis displaying early on-treatment Virologic response. PLoS One. 2017;12:e0168713.CrossRef
27.
Ioannou GN, Beste LA, Chang MF, Green PK, Lowy E, Tsui JI, Su F, Berry K. Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/ritonavir/Ombitasvir and Dasabuvir regimens for treatment of patients with hepatitis C in the veterans affairs National Health Care System. Gastroenterology. 2016;151:457–71.CrossRef
28.
Crespo J, Calleja JL, Fernández I, Sacristan B, Ruiz-Antorán B, Ampuero J, Hernández-Conde M, García-Samaniego J, Gea F, Buti M, Cabezas J, Lens S, Morillas RM, Salcines JR, Pascasio JM, Turnes J, Sáez-Royuela F, Arenas J, Rincón D, Prieto M, Jorquera F, Sanchez Ruano JJ, Navascués CA, Molina E, Moya AG, Moreno-Planas JM. Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collaborating Group. Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection. Clin Gastroenterol Hepatol. 2017;15:945–9.CrossRef
29.
Welzel TM, Hinrichsen H, Sarrazin C, Buggisch P, Baumgarten A, Christensen S, Berg T, Mauss S, Teuber G, Stein K, Deterding K, van Bömmel F, Heyne R, John C, Zimmermann T, Lutz T, Schott E, Hettinger J, Kleine H, König B, Hüppe D, Wedemeyer H. Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German hepatitis C registry. J Viral Hepat. 2017;24:840–9.CrossRef
30.
Perelló C, Carrión JA, Ruiz-Antorán B, Crespo J, Turnes J, Llaneras J, Lens S, Delgado M, García-Samaniego J, García-Paredes F, Fernández I, Morillas RM, Rincón D, Porres JC, Prieto M, Lázaro Ríos M, Fernández-Rodríguez C, Hermo JA, Rodríguez M, Herrero JI, Ruiz P, Fernández JR, Macías M, Pascasio JM, Moreno JM, Serra MÁ, Arenas J, Real Y, Jorquera F, Calleja JL. Spanish Collaborative Group for the Study of the Use of Hepatitis C Direct-Acting Drugs. Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1–4 chronic hepatitis C virus infection. J Viral Hepat. 2017;24:226–37.CrossRef
31.
Petta S, Marzioni M, Russo P, Aghemo A, Alberti A, Ascione A, Antinori A, Bruno R, Bruno S, Chirianni A, Gaeta GB, Giannini EG, Merli M, Messina V, Montilla S, Perno CF, Puoti M, Raimondo G, Rendina M, Silberstein FC, Villa E, Zignego AL, Pani L, Craxì A. ABACUS study group; AIFA team. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study. Lancet Gastroenterol Hepatol. 2017;2:427–34.CrossRef
32.
Wedemeyer H, Craxí A, Zuckerman E, Dieterich D, Flisiak R, Roberts SK, Pangerl A, Zhang Z, Martinez M, Bao Y, Calleja JL. Real-world effectiveness of Ombitasvir/Paritaprevir/ritonavir ± Dasabuvir ± ribavirin in patients with HCV genotype 1 or 4 infection: a meta-analysis. J Viral Hepat. 2017;24:936–43.CrossRef
33.
Komatsu TE, Boyd S, Sherwat A, Tracy L, Naeger LK, O'Rear JJ, Harrington PR. Regulatory analysis of effects of hepatitis C virus NS5A polymorphisms on efficacy of Elbasvir and Grazoprevir. Gastroenterology. 2017;152:586–97.CrossRef
34.
Maria C, Michael S, Susanne C, Catarina S, Ola W. INF-free sofosbuvir-based treatment of post-transplant hepatitis C relapse – a Swedish real life experience. Scand J Gastroenterol. 2017;52:585–8.CrossRef
35.
36.
Babatin MA, Alghamdi AS, Albenmousa A, Alaseeri A, Aljarodi M, Albiladi H, Alsahafi A, Almugharbal M, Alothmani HS, Sanai FM, Bzeizi KI. Efficacy and safety of Simeprevir or Daclatasvir in combination with Sofosbuvir for the treatment of hepatitis C genotype 4 infection. J Clin Gastroenterol. 2017;52(5):452–7 [Epub ahead of print].CrossRef
37.
Abad S, Vega A, Hernández E, Mérida E, de Sequera P, Albalate M, Macías N, Milla M, López-Gómez JM. Universal sustained viral response to the combination of Ombitasvir/Paritaprevir/ritonavir and Dasabuvir with/without ribavirin in patients on hemodialysis infected with hepatitis C virus genotypes 1 and 4. Am J Nephrol. 2017;45:267–72.CrossRef
38.
Ponziani FR, Siciliano M, Lionetti R, Pasquazzi C, Gianserra L, D'Offizi G, Gasbarrini A, Pompili M. Effectiveness of Paritaprevir/ritonavir/Ombitasvir/Dasabuvir in hemodialysis patients with hepatitis C virus infection and advanced liver fibrosis: case reports. Am J Kidney Dis. 2017;70:297–300.CrossRef
39.
Abdel-Moneim A, Aboud A, Abdel-Gabbar M, Zanaty MI, Ramadan M. A sofosbuvir-based quadruple regimen is highly effective in HCV type 4-infected Egyptian patients with DAA treatment failure. J Hepatol. 2018;68:1313–5.CrossRef
40.
Abdel-Moneim A, Aboud A, Abdel-Gabbar M, Zanaty M, Ramadan M. Retreatment efficacy of Sofosbuvir/Ombitasvir/Paritaprevir/ritonavir + ribavirin for hepatitis C virus genotype 4 patients. Dig Dis Sci. 2018;63(5):1341–7.CrossRef
41.
Abdel-Moneim A, Aboud A, Abdel-Gabaar M, Zanaty MI, Ramadan M. Efficacy and safety of sofosbuvir plus daclatasvir with or without ribavirin: large real-life results of patients with chronic hepatitis C genotype 4. Hepatol Int. 2018;12(4):348–55.CrossRef
42.
Kwo PY, Poordad F, Asatryan A, Wang S, Wyles DL, Hassanein T, Felizarta F, Sulkowski MS, Gane E, Maliakkal B, Overcash JS, Gordon SC, Muir AJ, Aguilar H, Agarwal K, Dore GJ, Lin CW, Liu R, Lovell SS, Ng TI, Kort J, Mensa FJ. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol. 2017;67:263–71.CrossRef
43.
Antaki N, Craxi A, Kamal S, et al. The neglected hepatitis C virus genotypes 4, 5 and 6: an international consensus report. Liver Int. 2010;30:342–55.CrossRef
44.
45.
46.
Manns M, Samuel D, Gane EJ, Mutimer D, Mc Caughan G, Buti M, Prieto M, Calleja JL, Peck-Radosavljevic M, Müllhaupt B, Agarwal K, Angus P, Yoshida EM, Colombo M, Rizzetto M, Dvory-Sobol H, Denning J, Arterburn S, Pang PS, Brainard D, JG MH, Dufour JF, Van Vlierberghe H, van Hoek B. Forns X; SOLAR-2 investigators. 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;16:685–97.CrossRef
Metadata
Title
Treatment of hepatitis C virus genotype 4 in the DAA era
Authors
Antonio Di Biagio
Lucia Taramasso
Giovanni Cenderello
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2018
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-018-1094-4

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