Hepatitis C is an infection caused by the hepatitis C virus that attacks the liver and leads to inflammation. The current standard-of-care regimens include a protease inhibitor — telaprevir or boceprevir — in combination with pegylated interferon and ribavirin. Hepatitis C treatment options on the horizon hold promise for better viral clearance with less toxicity than current regi mens. There are new data about new drugs, both direct-acting antivirals while minimizing intolerable side effects or adverse events. Developed new data from 4 phase 3 trials with the hepatitis C drug sofosbuvir and ribavirin show that a 12-week regimen is effective in treating HCV geno types 1 through 6. In the Annual Scientific Meeting and Postgraduate Course of the American College of Gastroenterology, different research was presented that was drawn from 4 phase 3 studies: NEUTRINO, FISSION, POSITRON and FUSION which enrolled different types of patients, who received Sofosbuvir with Peginterferon Alfa 2a and Ribavirin for 12 or 24 weeks in treatment; for all studies, the primary end point was sustained virologic response at 12 and 24 weeks posttreatment. In all studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. In conclusion, 2 novel direct-acting antiviral agents — sofosbuvir and simeprevir — target various components of the HCV ge nome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interac tions, and similar efficacy in all genotypes.
KeywordsHepatitis CSustained Virologic ResponseIntolerable Side Effects or Adverse EventsSofosbuvir and Simeprevir
Page, K., Morris, M.D., Hahn, J.A., Maher, L. and Prins, M. (2013) Injection Drug Use and Hepatitis C Virus Infection in Young Adult Injectors: Using Evidence to Inform Comprehensive Prevention. Clinical Infectious Diseases, 45, S32-S38.
Ghany, M.G., Nelson, D.R., Strader, D.B., Thomas, D.L. and Seeff, L.B. (2011) American Association for the Study of Liver Diseases. An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatology, 54, 1433-1444. http://dx.doi.org/10.1002/hep.24641 http://www.aasld.org/practiceguidelines/Documents/AASLDUpdateTreatmentGenotype1HCV11113.pdf
Hézode, C., Fontaine, H., Dorival, C., et al. (2013) CUPIC Study Group. Triple Therapy in Treatment-Experienced Patients with HCV-Cirrhosis in a Multicentre Cohort of the French Early Access Programme (ANRS CO20-CUPIC)-NCT01514890. Journal of Hepatology, 49, 434-441. http://dx.doi.org/10.1016/j.jhep.2013.04.035
Sulkowski, M.S., Cooper, C., Hunyady, B., et al. (2011) Management of Adverse Effects of Peg-IFN and Ribavirin Therapy for Hepatitis C. Nature Reviews Gastroenterology & Hepatology, 8, 212-223. http://dx.doi.org/10.1038/nrgastro.2011.21
Heim, M.H. (2013) 25 Years of Interferon-Based Treatment of Chronic Hepatitis C: An Epoch Coming to an End. Nature Reviews Immunology, 13, 535-342. http://dx.doi.org/10.1038/nri3463
Lewis, R. (2013) Hepatitis C: 6 Prevention Strategies That Work. http://www.medscape.com/viewarticle/808539
Ghany, M.G., Strader, D.B., Thomas, D.L. and Seeff, L.B. (2009) Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology, 46, 1335-1374. http://dx.doi.org/10.1002/hep.22759
Greg Fitz, M.D. (2013) Promising New Era in Hepatitis C Treatment. The Liver Meeting: American Association for the Study of Liver Diseases (AASLD), Washington DC, 11 November 2013.
Lawitz, E., Lalezari, J.P. and Hassanein, T. (2013) Sofosbuvir in Combination with Peginterferon Alfa-2a and Ribavirin for Non-Cirrhotic, Treatment-Naive Patients with Genotypes 1, 2, and 3 Hepatitis C Infection: A Randomised, Double-Blind, Phase 2 Trial. The Lancet Infectious Diseases, 13, 401-408. http://dx.doi.org/10.1016/S1473-3099(13)70033-1
Liver Center of Excellence at the Digestive Disease; Institute at the Virginia Mason Medical Center in Seattle, Washington (2013) Hepatitis C Drug Sofosbuvir Still Effective at 24 Weeks. American College of Gastroenterology (ACG) 2013 Annual Scientific Meeting and Postgraduate Course, San Diego, 11-16 October 2013, Abstract 38.
Kowdley, K.V., Lawitz, E., Crespo, I., et al. (2013) Sofosbuvir with Pegylated Interferon Alfa-2a and Ribavirin for Treatment-Naive Patients with Hepatitis C Genotype-1 Infection (ATOMIC): An Open-Label, Randomised, Multicentre Phase 2 Trial. Lancet, 381, 2100-2107.
Kowdley, K.V., Lawitz, E., Crespo, I., et al. (2013) Sofosbuvir with Pegylated Interferon Alfa-2a and Ribavirin for Treatment-Naive Patients with Hepatitis C Genotype-1 Infection (ATOMIC): An Open-Label, Randomised, Multicentre Phase 2 Trial. Lancet, 381, 2100-2107. http://dx.doi.org/10.1016/S0140-6736(13)60247-0
Lawitz, E., Mangia, A., Wyles, D., et al. (2013) Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection. The New England Journal of Medicine, 368, 1878-1887. http://dx.doi.org/10.1056/NEJMoa1214853
Lawitz, E., Ghalib, R., Rodriguez-Torres, M., et al. (2013) COSMOS Study: SVR4 Results of a Once Daily Regimen of Simeprevir (TMC435) plus Sofosbuvir (GS-7977) with or without Ribavirin in HCV Genotype 1 Null Responders. Program and Abstracts of the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, 3-6 March 2013, Abstract 155LB.
Jacobson, I.M., Gordon, S.C., Kowdley, K.V., et al. (2013) POSITRON Study; FUSION Study. Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options. The New England Journal of Medicine, 368, 1867-1877. http://dx.doi.org/10.1056/NEJMoa1214854
Poordad, F., Lawitz, E., Kowdley, K.V., et al. (2013) Exploratory Study of Oral Combination Antiviral Therapy for Hepatitis C. The New England Journal of Medicine, 386, 45-53. http://dx.doi.org/10.1056/NEJMoa1208809
Lawitz, E., Poordad, F., Pang, P.S., et al. (2013) Sofosbuvir and Ledipasvir Fixed-Dose Combination with and without Ribavirin in Treatment-Naive and Previously Treated Patients with Genotype 1 Hepatitis C Virus Infection (LONE-STAR): An Open-Label, Randomised, Phase 2 Trial. The Lancet, 383, 515-523.
Lawitz, E.J., Gruener, D., Hill, J.M., et al. (2012) A Phase 1, Randomized, Placebo-Controlled, 3-Day, Dose-Ranging Study of GS-5885, an NS5A Inhibitor, in Patients with Genotype 1 Hepatitis C. Journal of Hepatology, 57, 24-31.
Cheng, G., Peng, B., Corsa, A., et al. (2012) Antiviral Activity and Resistance Profile of the Novel HCV NS5A Inhibitor GS-5885. Journal of Hepatology, 56, S464.
Zeuzem, S., Dusheiko, G.M., Salupere, R., et al. (2013) Sofosbuvir + Ribavirin for 12 or 24 Weeks for Patients with HCV Genotype 2 or 3: The VALENCE Trial. Program and abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract 1085.
Jacobson, I., Ghalib, R.H., Rodriguez-Torres, M., et al. (2013) 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-Naïve and Prior Null Responder Patients: The COSMOS Study. Program and Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract LB-3.
Gane, E.J., Stedman, C.A., Hyland, R.H., et al. (2013) Once Daily Sofosbuvir/Ledipasvir Fixed Dose Combination with or without Ribavirin: The ELECTRON Trial. Program and Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract 21.
Sulkowski, M.S., Rodriguez-Torres, M., Lalezari, J.P., et al. (2013) 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). Program and Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract 212.
Cure, S., Guerra, I. and Dusheiko, G. (2013) Long-Term Outcomes of Sofosbuvir (SOF) for the Treatment of Chronic Hepatitis C Infected (CHC) Patients. Program and Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract 1107.
Charlton, M.R., Gane, E.J., Manns, M.P., et al. (2013) Sofosbuvir and Ribavirin for the Treatment of Established Recurrent Hepatitis C Infection after Liver Transplantation: Preliminary Results of a Prospective, Multicenter Study. Program and Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract LB-2.
Curry, R., Forns, X., Chung, R.T., et al. (2013) Pretransplant Sofosbuvir and Ribavirin to Prevent Recurrence of HCV Infection after Liver Transplantation. Program and Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC, 1-5 November 2013, Abstract 213.
Aronsohn, A., Reau, N. and Jensen, D. (in Press) Preparing for the Uncertain yet Inevitable: Off Label Combinations of Antiviral Agents in HCV. Hepatology.