title: Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation.
abstract: OBJECTIVE
  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.affiliation: Mayo Clinic, Rochester, Minnesota. Electronic address: michael.charlton@imail.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Charlton
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Columbia University, New York, New York.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Indiana School of Medicine, Indianapolis, Indiana.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
authors.affiliation: University of Michigan, Ann Arbor, Michigan.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Kansas University Medical Center, Kansas City, Kansas.
authors.forename: Richard
authors.initials: R
authors.lastname: Gilroy
authors.affiliation: NYU Medical Center, New York, New York.
authors.forename: Lewis
authors.initials: L
authors.lastname: Teperman
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana
authors.initials: D
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Brian
authors.initials: B
authors.lastname: Kirby
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Hadas
authors.initials: H
authors.lastname: Dvory-Sobol
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Jill
authors.initials: J
authors.lastname: Denning
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Sarah
authors.initials: S
authors.lastname: Arterburn
authors.affiliation: AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, and Université Paris Sud, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: University of California at San Francisco, San Francisco, California.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D009520:New Zealand; D010865:Pilot Projects; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069474:Sofosbuvir; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir
keywords: Antiviral Agent; Clinical Trial; DAA; NS5B Polymerase Inhibitor