An interferon-free antiviral regimen for HCV after liver transplantation

Paul Y. Kwo, Parvez S. Mantry, Eoin Coakley, Helen S. Te, Hugo E. Vargas, Robert Brown, Fredric Gordon, Josh Levitsky, Norah A. Terrault, James R. Burton, Wangang Xie, Carolyn Setze, Prajakta Badri, Tami Pilot-Matias, Regis A. Vilchez, Xavier Forns

Research output: Contribution to journalArticle

277 Citations (Scopus)

Abstract

Background: Hepatitis C virus (HCV) infection is the leading indication for liver transplantation worldwide, and interferon-containing regimens are associated with low response rates owing to treatment-limiting toxic effects in immunosuppressed liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection.

Methods: We enrolled 34 liver-transplant recipients with no fibrosis or mild fibrosis, who received ombitasvir-ABT-450/r (at a once-daily dose of 25 mg of ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and subsequent dose modifications for anemia were at the investigator's discretion. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment.

Results: Of the 34 study participants, 33 had a sustained virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95% confidence interval, 85 to 100). The most common adverse events were fatigue, headache, and cough. Five patients (15%) required erythropoietin; no patient required blood transfusion. One patient discontinued the study drugs owing to adverse events after week 18 but had a sustained virologic response. Blood levels of calcineurin inhibitors were monitored, and dosages were modified to maintain therapeutic levels; no episode of graft rejection was observed during the study.

Conclusions: Treatment with the multitargeted regimen of ombitasvir-ABT-450/r and dasabuvir with ribavirin was associated with a low rate of serious adverse events and a high rate of sustained virologic response among liver-transplant recipients with recurrent HCV genotype 1 infection, a historically difficult-to-treat population.

Original languageEnglish (US)
Pages (from-to)2375-2382
Number of pages8
JournalNew England Journal of Medicine
Volume371
Issue number25
DOIs
StatePublished - Dec 18 2014

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Hepacivirus
Liver Transplantation
Interferons
Ribavirin
Antiviral Agents
Ritonavir
Liver
Fibrosis
Genotype
Primary Headache Disorders
Therapeutics
Poisons
Graft Rejection
Virus Diseases
Erythropoietin
Infection
Protease Inhibitors
Blood Transfusion
Fatigue
Anemia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kwo, P. Y., Mantry, P. S., Coakley, E., Te, H. S., Vargas, H. E., Brown, R., ... Forns, X. (2014). An interferon-free antiviral regimen for HCV after liver transplantation. New England Journal of Medicine, 371(25), 2375-2382. https://doi.org/10.1056/NEJMoa1408921

An interferon-free antiviral regimen for HCV after liver transplantation. / Kwo, Paul Y.; Mantry, Parvez S.; Coakley, Eoin; Te, Helen S.; Vargas, Hugo E.; Brown, Robert; Gordon, Fredric; Levitsky, Josh; Terrault, Norah A.; Burton, James R.; Xie, Wangang; Setze, Carolyn; Badri, Prajakta; Pilot-Matias, Tami; Vilchez, Regis A.; Forns, Xavier.

In: New England Journal of Medicine, Vol. 371, No. 25, 18.12.2014, p. 2375-2382.

Research output: Contribution to journalArticle

Kwo, PY, Mantry, PS, Coakley, E, Te, HS, Vargas, HE, Brown, R, Gordon, F, Levitsky, J, Terrault, NA, Burton, JR, Xie, W, Setze, C, Badri, P, Pilot-Matias, T, Vilchez, RA & Forns, X 2014, 'An interferon-free antiviral regimen for HCV after liver transplantation', New England Journal of Medicine, vol. 371, no. 25, pp. 2375-2382. https://doi.org/10.1056/NEJMoa1408921
Kwo PY, Mantry PS, Coakley E, Te HS, Vargas HE, Brown R et al. An interferon-free antiviral regimen for HCV after liver transplantation. New England Journal of Medicine. 2014 Dec 18;371(25):2375-2382. https://doi.org/10.1056/NEJMoa1408921
Kwo, Paul Y. ; Mantry, Parvez S. ; Coakley, Eoin ; Te, Helen S. ; Vargas, Hugo E. ; Brown, Robert ; Gordon, Fredric ; Levitsky, Josh ; Terrault, Norah A. ; Burton, James R. ; Xie, Wangang ; Setze, Carolyn ; Badri, Prajakta ; Pilot-Matias, Tami ; Vilchez, Regis A. ; Forns, Xavier. / An interferon-free antiviral regimen for HCV after liver transplantation. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 25. pp. 2375-2382.
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AU - Kwo, Paul Y.

AU - Mantry, Parvez S.

AU - Coakley, Eoin

AU - Te, Helen S.

AU - Vargas, Hugo E.

AU - Brown, Robert

AU - Gordon, Fredric

AU - Levitsky, Josh

AU - Terrault, Norah A.

AU - Burton, James R.

AU - Xie, Wangang

AU - Setze, Carolyn

AU - Badri, Prajakta

AU - Pilot-Matias, Tami

AU - Vilchez, Regis A.

AU - Forns, Xavier

PY - 2014/12/18

Y1 - 2014/12/18

N2 - Background: Hepatitis C virus (HCV) infection is the leading indication for liver transplantation worldwide, and interferon-containing regimens are associated with low response rates owing to treatment-limiting toxic effects in immunosuppressed liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection.Methods: We enrolled 34 liver-transplant recipients with no fibrosis or mild fibrosis, who received ombitasvir-ABT-450/r (at a once-daily dose of 25 mg of ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and subsequent dose modifications for anemia were at the investigator's discretion. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment.Results: Of the 34 study participants, 33 had a sustained virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95% confidence interval, 85 to 100). The most common adverse events were fatigue, headache, and cough. Five patients (15%) required erythropoietin; no patient required blood transfusion. One patient discontinued the study drugs owing to adverse events after week 18 but had a sustained virologic response. Blood levels of calcineurin inhibitors were monitored, and dosages were modified to maintain therapeutic levels; no episode of graft rejection was observed during the study.Conclusions: Treatment with the multitargeted regimen of ombitasvir-ABT-450/r and dasabuvir with ribavirin was associated with a low rate of serious adverse events and a high rate of sustained virologic response among liver-transplant recipients with recurrent HCV genotype 1 infection, a historically difficult-to-treat population.

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