title: High post-transplant virological response in hepatitis C virus infected patients treated with pretransplant protease inhibitor-based triple therapy.
abstract: OBJECTIVE
  Prevention of recurrent hepatitis C virus (HCV) following liver transplant (LT) with pre-LT antiviral therapy is limited by poor tolerability and efficacy. We aimed to evaluate the safety and efficacy of NS3/4A protease inhibitor (PI)-based triple therapy in patients awaiting LT.
  
  
  METHODS
  Consecutive patients treated with triple therapy pre-LT from two centers were prospectively enrolled in an observational cohort. Overall 12 week sustained virological response (SVR12) was the primary outcome. Pre- and post-LT (pTVR) virological response rates and safety were secondary outcomes.
  
  
  RESULTS
  Twenty-nine patients (mean age 57.9, 79% male, 66% prior non-responders) were treated with telaprevir (93%) or boceprevir-based (7%) triple therapy for a median (range) of 27 (3-50) weeks, including a pegylated-interferon and ribavirin lead-in in 18%. Median (range) MELD at treatment was 8 (6-16), 39% had hepatocellular carcinoma and all patients were Child-Turcotte-Pugh class A (62%) or B (38%). Twelve patients underwent LT, 75% with undetectable viral load. The overall SVR12 rate was 52%, including pre-LT SVR12 of 41% in patients who completed treatment and follow-up on the wait list and pTVR12 of 67% among transplanted patients. The pTVR12 rate was 89% among those patients with undetectable viral load at LT. Serious adverse events occurred in nine (31%) patients including one (3%) on-treatment death and eight (28%) hospitalizations.
  
  
  CONCLUSIONS
  Overall SVR12 and pTVR12 rates are high among patients treated with PI-based triple therapy while awaiting LT, even in this difficult to treat population. However, caution is needed as early discontinuation and serious adverse events are common.
authors.affiliation: Division of Digestive and Liver Diseases, Center for Liver Disease and Transplantation, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Verna
authors.forename: Kirti
authors.initials: K
authors.lastname: Shetty
authors.forename: Thresiamma
authors.initials: T
authors.lastname: Lukose
authors.forename: Nicole
authors.initials: N
authors.lastname: Terry
authors.forename: Kimiknu
authors.initials: K
authors.lastname: Mentore
authors.forename: Sonja K
authors.initials: SK
authors.lastname: Olsen
authors.forename: Alyson N
authors.initials: AN
authors.lastname: Fox
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Dove
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
mesh_terms: D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D019562:Viral Load
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: Hepatitis C; liver transplant; protease inhibitor; treatment