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Review
. 2014 Jan;21(5):152-6.

Cure of hepatitis C virus infection without interferon alfa: scientific basis and current clinical evidence

David L Thomas  1
Affiliations
Review

Cure of hepatitis C virus infection without interferon alfa: scientific basis and current clinical evidence

David L Thomas. Top Antivir Med. 2014 Jan.

Abstract

Cure of hepatitis C virus (HCV) infection is achievable without interferon alfa through the use of new direct-acting antiviral (DAA) drugs. In this era of interferon alfa-sparing therapy, however, interferon alfa sensitivity still matters, even as it turns out, if interferon alfa is not used. Inclusion of ribavirin in the treatment regimen remains a factor in treatment response, as does duration of treatment. HCV genotype and subtype remain relevant considerations in choosing a treatment regimen, and viral resistance may emerge when treatment fails. The potency and barrier to resistance of new DAAs and the use of appropriately designed interferon alfa-sparing combinations can overcome obstacles to cure posed by HCV resistance, interferon alfa resistance, and differences in response based on HCV genotype and subtype. Studies demonstrating the use of new DAAs to overcome these obstacles are discussed. This article summarizes a presentation by David L. Thomas, MD, MPH, at the IAS-USA continuing education program held in New York, New York, in June 2013.

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Conflict of interest statement

Financial Affiliations: Dr Thomas has received grants awarded to his institution from Gilead Sciences, Inc, and Merck & Co, Inc.

Figures

Figure 1.
Figure 1.
Design of a trial evaluating the use of the investigational drugs faldaprevir and deleobuvir, with or without ribavirin, in 362 treatment-naive patients with genotype IL28B (CC or non-CC) and hepatitis C virus (HCV) genotype 1 (subtype 1a or 1b) infection. Thirty-three patients enrolled in the trial had compensated cirrhosis. BID indicates twice daily; QD, once daily; TID, thrice daily. Adapted with permission from Zeuzem et al.
Figure 2.
Figure 2.
Sustained virologic response (SVR) rates, by treatment group, in a trial evaluating the use of the investigational drugs faldaprevir and deleobuvir, with or without ribavirin, in treatment-naive patients with hepatitis C virus (HCV) genotype 1 infection. BID indicates twice daily; QD, once daily; SVR12, SVR 12 weeks after cessation of treatment; TID, thrice daily. Adapted with permission from Zeuzem et al.
Figure 3.
Figure 3.
Sustained virologic response (SVR) rates, by treatment group, in a trial evaluating the use of the investigational drugs faldaprevir and deleobuvir, with or without ribavirin, in treatment-naive patients with genotype IL28B (CC or non-CC) and hepatitis C virus (HCV) genotype 1 (subtype 1a or 1b) infection, stratified by patient genotype (top) and HCV subtype (bottom). BID indicates twice daily; QD, once daily; SVR12, SVR 12 weeks after cessation of treatment; TID, thrice daily. Adapted with permission from Zeuzem et al.
Figure 4.
Figure 4.
Sustained virologic response (SVR) rates, by treatment group, in a trial evaluating the use of the ritonavir-boosted (/r) investigational protease inhibitor ABT-450, the investigational nonstructural protein (NS) 5A (NS5A) inhibitor ABT-267, the investigational nonnucleoside NS5B inhibitor ABT-333, and ribavirin in 438 hepatitis C virus (HCV)-infected, treatment-naive patients and in 133 HCV-infected patients with prior nonresponse to interferon alfa. SVR12 indicates SVR 12 weeks after cessation of treatment; SVR24, SVR 24 weeks after cessation of treatment. Adapted with permission from Kowdley et al.
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References

Additional Suggested Reading

    1. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Eng J Med. 2013;368(20):1878-1887. - PubMed

References

    1. Hoofnagle JH, Mullen KD, Jones DB, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med. 1986;315(25):1575-1578. - PubMed
    1. Zeuzem S, Soriano V, Asselah T, et al. Interferon (IFN)-free combination treatment with the HCV NS3/4A protease inhibitor BI 201335 and the non-nucleoside NS5B inhibitor BI 207127 +/- ribavirin (R): final results of the SOUND-C2 and predictors of response [Abstract 232]. 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) November 9-13, 2012; Boston, Massachusetts.
    1. Zeuzem S, Soriano V, Asselah T, et al. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med. 2013;369(7):630-639. - PubMed
    1. Poordad F, Lawitz E, Kowdley KV, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013;368(1):45-53. - PubMed
    1. Kowdley K, Lawitz E, Poordad F, et al. A 12-week interferon-free treatment regimen with ABT-450/r, ABT-267, ABT-333 and ribavirin achieves SVR12 rates (observed data) of 99% in treatment-naive patients and 93% in prior null responders with HCV genotype 1 infection. 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) November 9-13, 2012; Boston, Massachusetts.

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