title: A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy.
abstract: OBJECTIVE
  NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited.
  
  
  METHODS
  This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12).
  
  
  RESULTS
  The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p<0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8g/dl and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related.
  
  
  CONCLUSIONS
  The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.
authors.affiliation: University of Colorado, Denver, Aurora, CO, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Burton
authors.affiliation: Baylor University Medical Center, Dallas, TX, United States.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.affiliation: Columbia University, New York, NY, United States.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Verna
authors.affiliation: University of California at San Francisco, San Francisco, CA, United States.
authors.forename: Varun
authors.initials: V
authors.lastname: Saxena
authors.affiliation: University of California at San Francisco, San Francisco, CA, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dodge
authors.affiliation: Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Stravitz
authors.affiliation: Northwestern University, Chicago, IL, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Levitsky
authors.affiliation: Baylor University Medical Center, Dallas, TX, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Trotter
authors.affiliation: University of Colorado, Denver, Aurora, CO, United States.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.affiliation: Columbia University, New York, NY, United States.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.affiliation: University of California at San Francisco, San Francisco, CA, United States. Electronic address: Norah.Terrault@ucsf.edu.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a
keywords: Antiviral therapy; Boceprevir; Interferon; Ribavirin; Telaprevir