Michael Charlton1, Edward Gane2, Michael P Manns3, Robert S Brown4, Michael P Curry5, Paul Y Kwo6, Robert J Fontana7, Richard Gilroy8, Lewis Teperman9, Andrew J Muir10, John G McHutchison11, William T Symonds11, Diana Brainard11, Brian Kirby11, Hadas Dvory-Sobol11, Jill Denning11, Sarah Arterburn11, Didier Samuel12, Xavier Forns13, Norah A Terrault14. 1. Mayo Clinic, Rochester, Minnesota. Electronic address: michael.charlton@imail.org. 2. Auckland City Hospital, Auckland, New Zealand. 3. Hannover Medical School, Hannover, Germany. 4. Columbia University, New York, New York. 5. Beth Israel Deaconess Medical Center, Boston, Massachusetts. 6. Indiana School of Medicine, Indianapolis, Indiana. 7. University of Michigan, Ann Arbor, Michigan. 8. Kansas University Medical Center, Kansas City, Kansas. 9. NYU Medical Center, New York, New York. 10. Duke University Medical Center, Durham, North Carolina. 11. Gilead Sciences, Foster City, California. 12. AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, and Université Paris Sud, Villejuif, France. 13. Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain. 14. University of California at San Francisco, San Francisco, California.
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. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.
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. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.
Authors: David Goldberg; Ivo C Ditah; Kia Saeian; Mona Lalehzari; Andrew Aronsohn; Emmanuel C Gorospe; Michael Charlton Journal: Gastroenterology Date: 2017-01-11 Impact factor: 22.682
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Authors: Neal Patel; Kian Bichoupan; Lawrence Ku; Rachana Yalamanchili; Alyson Harty; Donald Gardenier; Michel Ng; David Motamed; Viktoriya Khaitova; Nancy Bach; Charissa Chang; Priya Grewal; Meena Bansal; Ritu Agarwal; Lawrence Liu; Gene Im; Jennifer Leong; Leona Kim-Schluger; Joseph Odin; Jawad Ahmad; Scott Friedman; Douglas Dieterich; Thomas Schiano; Ponni Perumalswami; Andrea Branch Journal: World J Gastroenterol Date: 2016-03-07 Impact factor: 5.742