Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation

Michael Charlton, Edward Gane, Michael P. Manns, Robert S. Brown, Michael P. Curry, Paul Y. Kwo, Robert J. Fontana, Richard Gilroy, Lewis Teperman, Andrew J. Muir, John G. McHutchison, William T. Symonds, Diana Brainard, Brian Kirby, Hadas Dvory-Sobol, Jill Denning, Sarah Arterburn, Didier Samuel, Xavier Forns, Norah A. Terrault

Research output: Contribution to journalArticle

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Abstract

BACKGROUND & AIMS: Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. METHODS: In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. RESULTS: Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%-82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. CONCLUSIONS: Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection.

Original languageEnglish
Pages (from-to)108-117
Number of pages10
JournalGastroenterology
Volume148
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Ribavirin
Virus Diseases
Hepacivirus
Liver Transplantation
Interferons
Immunosuppressive Agents
Therapeutics
Transplantation
Genotype
Sofosbuvir
Interferon-alpha
Fatigue
Headache
Anemia
Diarrhea
Creatinine
Hemoglobins
Fibrosis
Nucleotides
Confidence Intervals

Keywords

  • Antiviral Agent
  • Clinical Trial
  • DAA
  • NS5B Polymerase Inhibitor

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Charlton, M., Gane, E., Manns, M. P., Brown, R. S., Curry, M. P., Kwo, P. Y., ... Terrault, N. A. (2015). Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology, 148(1), 108-117. https://doi.org/10.1053/j.gastro.2014.10.001

Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. / Charlton, Michael; Gane, Edward; Manns, Michael P.; Brown, Robert S.; Curry, Michael P.; Kwo, Paul Y.; Fontana, Robert J.; Gilroy, Richard; Teperman, Lewis; Muir, Andrew J.; McHutchison, John G.; Symonds, William T.; Brainard, Diana; Kirby, Brian; Dvory-Sobol, Hadas; Denning, Jill; Arterburn, Sarah; Samuel, Didier; Forns, Xavier; Terrault, Norah A.

In: Gastroenterology, Vol. 148, No. 1, 01.01.2015, p. 108-117.

Research output: Contribution to journalArticle

Charlton, M, Gane, E, Manns, MP, Brown, RS, Curry, MP, Kwo, PY, Fontana, RJ, Gilroy, R, Teperman, L, Muir, AJ, McHutchison, JG, Symonds, WT, Brainard, D, Kirby, B, Dvory-Sobol, H, Denning, J, Arterburn, S, Samuel, D, Forns, X & Terrault, NA 2015, 'Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation', Gastroenterology, vol. 148, no. 1, pp. 108-117. https://doi.org/10.1053/j.gastro.2014.10.001
Charlton, Michael ; Gane, Edward ; Manns, Michael P. ; Brown, Robert S. ; Curry, Michael P. ; Kwo, Paul Y. ; Fontana, Robert J. ; Gilroy, Richard ; Teperman, Lewis ; Muir, Andrew J. ; McHutchison, John G. ; Symonds, William T. ; Brainard, Diana ; Kirby, Brian ; Dvory-Sobol, Hadas ; Denning, Jill ; Arterburn, Sarah ; Samuel, Didier ; Forns, Xavier ; Terrault, Norah A. / Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. In: Gastroenterology. 2015 ; Vol. 148, No. 1. pp. 108-117.
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