Sofosbuvir and ribavirin prevent recurrence of hcv infection after liver transplantation: An open-label study

Michael P. Curry, Xavier Forns, Raymond T. Chung, Norah A. Terrault, Robert Brown, Jonathan M. Fenkel, Fredric Gordon, Jacqueline O'Leary, Alexander Kuo, Thomas Schiano, Gregory Everson, Eugene R Schiff, Alex Befeler, Edward Gane, Sammy Saab, John G. McHutchison, G. Mani Subramanian, William T. Symonds, Jill Denning, Lindsay McNairSarah Arterburn, Evguenia Svarovskaia, Dilip Moonka, Nezam Afdhal

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence.

Original languageEnglish
Pages (from-to)100-107.e1
JournalGastroenterology
Volume148
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Ribavirin
Hepacivirus
Liver Transplantation
Recurrence
Transplantation
Infection
RNA
Sofosbuvir
Transplants
Hepatic Artery
Virus Diseases
Interferons
Antiviral Agents
Fatigue
Headache
Anemia
Hepatocellular Carcinoma
Thrombosis
Fibrosis
Genotype

Keywords

  • Direct-Acting Antiviral Agents
  • HCV Recurrence
  • Hepatitis C Virus
  • Liver Transplantation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Curry, M. P., Forns, X., Chung, R. T., Terrault, N. A., Brown, R., Fenkel, J. M., ... Afdhal, N. (2015). Sofosbuvir and ribavirin prevent recurrence of hcv infection after liver transplantation: An open-label study. Gastroenterology, 148(1), 100-107.e1. https://doi.org/10.1053/j.gastro.2014.09.023

Sofosbuvir and ribavirin prevent recurrence of hcv infection after liver transplantation : An open-label study. / Curry, Michael P.; Forns, Xavier; Chung, Raymond T.; Terrault, Norah A.; Brown, Robert; Fenkel, Jonathan M.; Gordon, Fredric; O'Leary, Jacqueline; Kuo, Alexander; Schiano, Thomas; Everson, Gregory; Schiff, Eugene R; Befeler, Alex; Gane, Edward; Saab, Sammy; McHutchison, John G.; Subramanian, G. Mani; Symonds, William T.; Denning, Jill; McNair, Lindsay; Arterburn, Sarah; Svarovskaia, Evguenia; Moonka, Dilip; Afdhal, Nezam.

In: Gastroenterology, Vol. 148, No. 1, 01.01.2015, p. 100-107.e1.

Research output: Contribution to journalArticle

Curry, MP, Forns, X, Chung, RT, Terrault, NA, Brown, R, Fenkel, JM, Gordon, F, O'Leary, J, Kuo, A, Schiano, T, Everson, G, Schiff, ER, Befeler, A, Gane, E, Saab, S, McHutchison, JG, Subramanian, GM, Symonds, WT, Denning, J, McNair, L, Arterburn, S, Svarovskaia, E, Moonka, D & Afdhal, N 2015, 'Sofosbuvir and ribavirin prevent recurrence of hcv infection after liver transplantation: An open-label study', Gastroenterology, vol. 148, no. 1, pp. 100-107.e1. https://doi.org/10.1053/j.gastro.2014.09.023
Curry, Michael P. ; Forns, Xavier ; Chung, Raymond T. ; Terrault, Norah A. ; Brown, Robert ; Fenkel, Jonathan M. ; Gordon, Fredric ; O'Leary, Jacqueline ; Kuo, Alexander ; Schiano, Thomas ; Everson, Gregory ; Schiff, Eugene R ; Befeler, Alex ; Gane, Edward ; Saab, Sammy ; McHutchison, John G. ; Subramanian, G. Mani ; Symonds, William T. ; Denning, Jill ; McNair, Lindsay ; Arterburn, Sarah ; Svarovskaia, Evguenia ; Moonka, Dilip ; Afdhal, Nezam. / Sofosbuvir and ribavirin prevent recurrence of hcv infection after liver transplantation : An open-label study. In: Gastroenterology. 2015 ; Vol. 148, No. 1. pp. 100-107.e1.
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T2 - An open-label study

AU - Curry, Michael P.

AU - Forns, Xavier

AU - Chung, Raymond T.

AU - Terrault, Norah A.

AU - Brown, Robert

AU - Fenkel, Jonathan M.

AU - Gordon, Fredric

AU - O'Leary, Jacqueline

AU - Kuo, Alexander

AU - Schiano, Thomas

AU - Everson, Gregory

AU - Schiff, Eugene R

AU - Befeler, Alex

AU - Gane, Edward

AU - Saab, Sammy

AU - McHutchison, John G.

AU - Subramanian, G. Mani

AU - Symonds, William T.

AU - Denning, Jill

AU - McNair, Lindsay

AU - Arterburn, Sarah

AU - Svarovskaia, Evguenia

AU - Moonka, Dilip

AU - Afdhal, Nezam

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N2 - BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence.

AB - BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence.

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KW - HCV Recurrence

KW - Hepatitis C Virus

KW - Liver Transplantation

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