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Current Infectious Disease Reports
Erschienen in: Current Infectious Disease Reports 8/2014

01.08.2014 | Transplant and Oncology (M Ison, Section Editor)

The Current State and Future Prospects of Chronic Hepatitis C Virus Infection Treatment

verfasst von: Christopher Moore, Josh Levitsky

Erschienen in: Current Infectious Disease Reports | Ausgabe 8/2014

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Abstract

Hepatitis C virus (HCV) infection is a significant cause of chronic liver disease with substantial long-term sequelae. Until very recently, therapies to cure HCV were hindered by high nonresponse rates and severe side effects. The first-generation protease inhibitor-containing regimens provided superior cure rates for many HCV-infected patients, although their side-effect profile proved to be quite burdensome. We are now witnessing the emergence of therapies with superior cure rates, limited side effects, and broad genotypic activity. Two therapies, sofosbuvir (an NS5b polymerase inhibitor) and simeprevir (a second-generation NS3/4A protease inhibitor), were approved by the Food and Drug Administration in late 2013 for use in a number of HCV populations. This review focuses primarily upon these therapies and the key studies that support their use in practice. Furthermore, representative novel antiviral therapies, in advanced stages of testing, are also reviewed.
Literatur
1.
Alter HJ, Holland PV, Purcell RH. The emerging pattern of post-transfusion hepatitis. Am J Med Sci. 1975;270(2):329–34.PubMedCrossRef
2.
Alter HJ, Purcell RH, Shih JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med. 1989;321(22):1494–500.PubMedCrossRef
3.•
Alter HJ. The road not taken or how I learned to love the liver: a personal perspective on hepatitis history. Hepatology. 2014;59(1):4–12. An interesting history regarding the difficulties in the identification and diagnosis of the Hepatitis C virus.PubMedCrossRef
4.
Walsh JH, Purcell RH, Morrow AG, et al. Posttransfusion hepatitis after open-heart operations. Incidence after the administration of blood from commercial and volunteer donor populations. JAMA. 1970;211(2):261–5.PubMedCrossRef
5.
6.
Terrault N. Liver transplantation in the setting of chronic HCV. Best Pract Res Clin Gastroenterol. 2012;26(4):531–48.PubMedCrossRef
7.
Strassburg CP, Manns MP. Liver transplantation: indications and results. Internist (Berl). 2009;50(5):550–60.CrossRef
8.
9.
Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis. 2011;52(7):889–900.PubMedCrossRef
10.
Dusheiko G, Main J, Thomas H, et al. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study. J Hepatol. 1996;25(5):591–8.PubMedCrossRef
11.
Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989;321(22):1501–6.PubMedCrossRef
12.
Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998;352(9138):1426–32.PubMedCrossRef
13.
McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339(21):1485–92.PubMedCrossRef
14.
Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med. 2000;343(23):1666–72.PubMedCrossRef
15.
Lindsay KL, Trepo C, Heintges T, et al. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology. 2001;34(2):395–403.PubMedCrossRef
16.
Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–65.PubMedCrossRef
17.
Hinrichsen H, Benhamou Y, Wedemeyer H, et al. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology. 2004;127(5):1347–55.PubMedCrossRef
18.
19.
Kwo P, Lawitz EJ, McCone J, et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010;376(9742):705–16.PubMedCrossRef
20.
Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405–16.PubMedCrossRef
21.
Hezode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360(18):1839–50.PubMedCrossRef
22.
Simeprevir (Olysio) for chronic hepatitis C. Med Lett Drugs Ther. 2014;56(1433):1–3.
23.
24.
Traynor K. Sofosbuvir approved for chronic hepatitis C infection. Am J Health Syst Pharm. 2014;71(2):90.
25.
Lawitz E, Gane EJ. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;369(7):678–9.PubMedCrossRef
26.
A Special Meeting Review Edition. Advances in the treatment of hepatitis C virus infection from EASL 2013. The 48th Annual Meeting of the European Association for the Study of the Liver, 24–28 April 2013, Amsterdam. Gastroenterol Hepatol (N.Y.). 2013(6 Suppl 3):1–18.
27.
Witkop B. Paul Ehrlich and his magic bullets – revisited. Proc Am Philos Soc. 1999;143(4):540–57.PubMed
28.
Back D, Else L. The importance of drug-drug interactions in the DAA era. Dig Liver Dis. 2013;45 Suppl 5:S343–8.PubMedCrossRef
29.
Kiser J, Burton J, Everson G. Drug-drug interactions during antiviral therapy for chronic hepatitis C. Nat Rev Gastroenterol Hepatol. 2013;10(10):596–606.PubMedCrossRef
30.
Jacobson I, Dore G, Foster G. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naive patients: efficacy in difficult-to-treat patient sub-populations in the QUEST 1 and 2 phase III trials. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC, 1–5 November 2013; Abstract 1122.
31.
Lawitz E, Forns X, Zeuzem S. Simeprevir (TMC-435) peginterferon/ribavirin for treatment of chronic HCV genotype-1 infection in patients who relapsed after previous interferon based therapy: results from PROMISE, a phase III trial. Digestive Disease Week 2013; Abstract 869.
32.
Zeuzem S, Berg T, Gane E. TMC435 in HCV genotype 1 patients who have failed previous pegylated interferon/ribavirin treatment: final SVR24 results of the ASPIRE trial. Proceedings of the 47th Annual Meeting of the European Association for the Study of the Liver; 18–22 April 2012; Barcelona, Spain. Abstract 2.
33.••
Jacobson I, Ghalib R, Rodriguez-Torres M. SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naive and prior null responder patients: the COSMOS study. Proceedings of the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013); 1–5 November 2013; Washington, DC. Abstract LB-3. Initial results of an important study utilizing both FDA-approved oral therapies together, without ribavirin or pegylated-interferon. Additionally there were strong cure rates in traditionally difficult to treat patients.
34.••
35.
European Association for Study of Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):392–420.CrossRef
36.
37.
Koff RS. Review article: the efficacy and safety of sofosbuvir, a novel, oral nucleotide NS5B polymerase inhibitor, in the treatment of chronic hepatitis C virus infection. Aliment Pharmacol Ther. 2014;39(5):478–87.PubMedCrossRef
38.
39.
Sofosbuvir (Sovaldi) for chronic hepatitis C. Med Lett Drugs Ther. 2014;56(1434):5–6.
40.
Lawitz E, Mangia A, Wyles D. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87.PubMedCrossRef
41.
Gane E, Lawitz E, Rodriguez-Torres M. Phase 3 randomized controlled trial of all-oral treatment with sofosbuvir+ribavirin for 12 weeks compared to 24 weeks of peg+ribavirin in treatment-naive GT2/3 HCV-infected patients (FISSION). Proceedings of the 48th Annual Meeting of the European Association for the Study of the Liver; 24–28 April 2013; Amsterdam. Abstract 5.
42.
Jacobson I, Yoshida E, Sulkowski M. Treatment with sofosbuvir + ribavirin for 12 weeks achieves SVR12 of 78% in GT2/3 interferon-ineligible, -intolerant, or -unwilling patients: results of the phase 3 POSITRON trial. Proceedings of the 48th Annual Meeting of the European Association for the Study of the Liver; 24–28 April 2013; Amsterdam. Abstract 61.
43.
Nelson D, Feld J, Kowdley K. All overall therapy with sofosbuvir + ribavirin for 12 or 16 weeks in treatment experienced GT2/3 HCV-infected patients: results of the phase 3 FUSION trial. Proceedings of the 48th Annual Meeting of the European Association for the Study of the Liver; 24–28 April 2013; Amsterdam. Abstract 6.
44.
Zeuzem S, Dusheiko G, Salupere R. Sofosbuvir + ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial. Proceedings of the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013); 1–5 November 2013; Washington, DC. Abstract 1085.
45.
Sulkowski M, Rodriguez-Torres M, Lalezari J. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1). Proceedings of the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013); 1–5 November 2013; Washington, DC. Abstract 212.
46.
Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.PubMedCrossRef
47.••
Curry M, Forns X, Chung R. Pretransplant sofosbuvir and ribavirin to prevent recurrence of HCV infection after liver transplantation. Proceedings of the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013); 1–5 November 2013; Washington, DC. Abstract 213. Important study detailing the efficacy of this therapy administered before liver transplantation in achieving SVR-12 weeks after liver transplantation. Additionally, the study demonstrates important guidance on duration of therapy before liver transplantation and duration of viral negativity before liver transplantation to achieve this SVR.
48.
49.
Sulkowski M, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370(3):211–21.PubMedCrossRef
50.
Dore G, Lawitz E, Hezode C. Daclatasvir combined with peginterferon alfa-2a and ribavirin for 12 or 16 weeks in patients with HCV genotype 2 or 3 infection: COMMAND GT2/3 study. Proceedings of the 48th Annual Meeting of the European Association for the Study of the Liver; 24–28 April 2013; Amsterdam. Abstract 1418.
51.
Kowdley K, Lawitz E, Poordad F, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014;370(3):222–32.PubMedCrossRef
52.
53.
Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383(9916):515–23.PubMedCrossRef
54.••
Gilead. Gilead announces SVR12 rates from three phase 3 studies evaluating a once-daily fixed-dose combination of sofosbuvir ledipasvir for genotype 1 hepatitis C patients. Foster City, CA: Gilead Sciences. http://​www.​gilead.​com/​news/​press-releases/​2013/​12/​gilead-announces-svr12-rates-from-three-phase-3-studies-evaluating-a-oncedaily-fixeddose-combination-of-sofosbuvir-and-ledipasvir-for-genotype-1-hepatitis-c-patients.​ Accessed 13 May 2014. The ION trials were important in demonstrating high SVR rates in a diverse group of genotype 1 patients, including a treatment-experienced cohort. This trial also used a fixed-dose combination of sofosbuvir and daclatasvir, i.e. one pill – a significant achievement in design compared to prior therapies requiring a multitude of pills per day (and injections).
55.
Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707–13.PubMedCrossRef
56.
Charlton M, et al. Sofosbuvir and ribavirin for the treatment of established recurrent hepatitis C infection after liver transplantation: preliminary results of a prospective, multicenter study. Proceedings of the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013); 1–5 November 2013; Washington, DC. Abstract LB-2.
57.
ClinicalTrials.gov. An expanded access phase 2 study of sofosbuvir with ribavirin and with or without pegylated interferon for 24 weeks in subjects who have undergone liver transplantation and who have aggressive, recurrent hepatitis C infection. http://​clinicaltrials.​gov/​ct2/​show/​NCT01779518.​ Accessed 13 May 2014.
58.
Fontana RJ, Hughes EA, Bifano M, et al. Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C. Am J Transplant. 2013;13(6):1601–5.PubMedCrossRef
59.
Fleming KM, Aithal GP, Card TR, West J. The rate of decompensation and clinical progression of disease in people with cirrhosis: a cohort study. Aliment Pharmacol Ther. 2010;32(11–12):1343–50.PubMedCrossRef
60.
Firpi RJ, Clark V, Soldevila-Pico C, et al. The natural history of hepatitis C cirrhosis after liver transplantation. Liver Transpl. 2009;15(9):1063–71.PubMedCrossRef
61.
Werner CR, Egetemeyr DP, Lauer UM, et al. Telaprevir-based triple therapy in liver transplant patients with hepatitis C virus: a 12-week pilot study providing safety and efficacy data. Liver Transpl. 2012;18(12):1464–70.PubMedCrossRef
62.
Coilly A, Roche B, Samuel D. Current management and perspectives for HCV recurrence after liver transplantation. Liver Int. 2013;33 Suppl 1:56–62.PubMedCrossRef
Metadaten
Titel
The Current State and Future Prospects of Chronic Hepatitis C Virus Infection Treatment
verfasst von
Christopher Moore
Josh Levitsky
Publikationsdatum
01.08.2014
Verlag
Springer US
Erschienen in
Current Infectious Disease Reports / Ausgabe 8/2014
Print ISSN: 1523-3847
Elektronische ISSN: 1534-3146
DOI
https://doi.org/10.1007/s11908-014-0413-1

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