title: Telaprevir- and Boceprevir-based Triple Therapy for Hepatitis C in Liver Transplant Recipients With Advanced Recurrent Disease: A Multicenter Study.
abstract: BACKGROUND
  Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis.
  
  
  METHODS
  The LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety.
  
  
  RESULTS
  Forty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation.
  
  
  CONCLUSIONS
  For LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.
authors.affiliation: 1 Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University, New York, NY. 2 Division of Gastroenterology and Hepatology, University of California, San Francisco, CA. 3 Division of Gastroenterology and Hepatology, University of Colorado, Denver, Aurora, CO. 4 Division of Hepatology and Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 5 Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA. 6 Department of Gastroenterology and Hepatology, Northwestern University, Chicago, IL.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Verna
authors.forename: Varun
authors.initials: V
authors.lastname: Saxena
authors.forename: James R
authors.initials: JR
authors.lastname: Burton
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dodge
authors.forename: Richard T
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Josh
authors.initials: J
authors.lastname: Levitsky
authors.forename: James F
authors.initials: JF
authors.lastname: Trotter
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002779:Cholestasis / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000401:mortality; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000401:mortality / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D009842:Oligopeptides; D012367:RNA, Viral; 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