title: Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study.
abstract: OBJECTIVE
  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. ClinicalTrials.gov: NCT01559844.
authors.affiliation: Transplant Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: mcurry@bidmc.harvard.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Liver Unit, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: GI Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Division of Gastroenterology, University of California San Francisco, San Francisco, California.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
authors.affiliation: Center for Liver Diseases and Transplantation, Columbia University, New York, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.affiliation: Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Fenkel
authors.affiliation: Liver Transplantation & Hepatology, Lahey Clinic, Burlington, Massachusetts.
authors.forename: Fredric
authors.initials: F
authors.lastname: Gordon
authors.affiliation: Transplant Hepatology, Baylor University Medical Center, Dallas, Texas.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: O'Leary
authors.affiliation: Liver Transplantation, University of California, San Diego, La Jolla, California.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kuo
authors.affiliation: Liver Diseases, Mount Sinai School of Medicine, New York, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schiano
authors.affiliation: Section of Hepatology, University of Colorado, Denver, Colorado.
authors.forename: Gregory
authors.initials: G
authors.lastname: Everson
authors.affiliation: Center for Liver Disease, University of Miami, Miami, Florida.
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.affiliation: Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri.
authors.forename: Alex
authors.initials: A
authors.lastname: Befeler
authors.affiliation: New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Sammy
authors.initials: S
authors.lastname: Saab
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: G Mani
authors.initials: GM
authors.lastname: Subramanian
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: Jill
authors.initials: J
authors.lastname: Denning
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Lindsay
authors.initials: L
authors.lastname: McNair
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Sarah
authors.initials: S
authors.lastname: Arterburn
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.affiliation: Gastroenterology, Henry Ford Health System, Detroit, Michigan.
authors.forename: Dilip
authors.initials: D
authors.lastname: Moonka
authors.affiliation: Transplant Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000401:mortality / Q000601:surgery* / Q000821:virology; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000401:mortality / Q000601:surgery* / Q000821:virology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load; D014850:Waiting Lists
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir
keywords: Direct-Acting Antiviral Agents; HCV Recurrence; Hepatitis C Virus; Liver Transplantation