title: Increased duration of dual pegylated interferon and ribavirin therapy for genotype 1 hepatitis C post-liver transplantation increases sustained virologic response: a retrospective review.
abstract: OBJECTIVE
  In patients with advanced post-transplant hepatitis C virus (HCV) recurrence, antiviral treatment (AVT) with interferon and ribavirin is indicated to prevent graft failure. The aim of this study was to determine and report Canadian data with respect to the safety, efficacy, and spontaneous virologic response (SVR) predictors of AVT among transplanted patients with HCV recurrence.
  
  
  METHODS
  A retrospective chart review was performed on patients transplanted in London, Ontario and Edmonton, Alberta from 2002 to 2012 who were treated for HCV. Demographic, medical, and treatment information was collected and analyzed.
  
  
  RESULTS
  A total of 85 patients with HCV received pegylated interferon with ribavirin post-liver transplantation and 28 of the 65 patients (43%) with genotype 1 achieved SVR. Of the patients having genotype 1 HCV who achieved SVR, there was a significantly lower stage of fibrosis (1.37 ± 0.88 vs. 1.89 ± 0.96; P = 0.03), increased ribavirin dose (total daily dose 1057 ± 230 vs. 856 ± 399 mg; P = 0.02), increased rapid virologic response (RVR) (6/27 vs. 0/31; P = 0.05), increased early virologic response (EVR) (28/28 vs. 18/35; P = 0.006), and longer duration of therapy (54.7 ± 13.4 weeks vs. 40.2 ± 18.7; P = 0.001). A logistic regression model using gender, age, RVR, EVR, anemia, duration of therapy, viral load, years' post-transplant, and type of organ (donation after cardiac death vs. donation after brain death) significantly predicted SVR (P < 0.001), with duration of therapy having a significant odds ratio of 1.078 (P = 0.007).
  
  
  CONCLUSIONS
  This study identified factors that predict SVR in HCV-positive patients who received dual therapy post-transplantation. Extending therapy from 48 weeks to 72 weeks of dual therapy is associated with increased SVR rates. Future studies examining the role of extended therapy are needed to confirm these findings, since the current study is a retrospective one.
authors.affiliation: Department of Gastroenterology and Hepatology, Western University, London, Canada.
authors.forename: Malcolm M
authors.initials: MM
authors.lastname: Wells
authors.forename: Lee S
authors.initials: LS
authors.lastname: Roth
authors.forename: Paul
authors.initials: P
authors.lastname: Marotta
authors.forename: Mark
authors.initials: M
authors.lastname: Levstik
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mason
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Bain
authors.forename: Natasha
authors.initials: N
authors.lastname: Chandok
authors.forename: Bandar M
authors.initials: BM
authors.lastname: Aljudaibi
mesh_terms: D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D017093:Liver Failure / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012367:RNA, Viral / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
references.citation: Gastroenterology. 2005 Sep;129(3):1031-41
references.pmid: 16143140
references.citation: Liver Transpl. 2012 Dec;18(12):1464-70
references.pmid: 22941516
references.citation: Health Technol Assess. 2004 Oct;8(39):iii-iv, 1-125
references.pmid: 15461877
references.citation: Hepatology. 1998 Sep;28(3):823-30
references.pmid: 9731579
references.citation: Transplantation. 2011 Aug 15;92(3):334-40
references.pmid: 21659948
references.citation: Hepatology. 2003 Nov;38(5):1282-8
references.pmid: 14578868
references.citation: Clin Transplant. 2004 Apr;18(2):166-73
references.pmid: 15016131
references.citation: Acta Med Croatica. 2009 Dec;63(5):451-7
references.pmid: 20198907
references.citation: Best Pract Res Clin Gastroenterol. 2012 Aug;26(4):531-48
references.pmid: 23199510
references.citation: Biochem Biophys Res Commun. 2006 May 12;343(3):879-84
references.pmid: 16564500
references.citation: Gut. 2002 Aug;51(2):248-52
references.pmid: 12117889
references.citation: Liver Transpl. 2010 Nov;16(11):1228-35
references.pmid: 21031537
references.citation: J Gastroenterol. 2003;38(6):567-72
references.pmid: 12825133
references.citation: Transplantation. 2009 Nov 27;88(10):1214-21
references.pmid: 19935376
references.citation: Gastroenterology. 2002 Apr;122(4):889-96
references.pmid: 11910340
references.citation: Liver Transpl. 2009 Jul;15(7):782-9
references.pmid: 19562715
references.citation: Am J Transplant. 2009 Aug;9(8):1707-13
references.pmid: 19538491
references.citation: Transplant Proc. 2005 Mar;37(2):1233-4
references.pmid: 15848679
references.citation: Hepatology. 2002 Jul;36(1):202-10
references.pmid: 12085366
references.citation: Liver Transpl. 2005 May;11(5):479-89
references.pmid: 15838917
references.citation: Antimicrob Agents Chemother. 2006 Sep;50(9):2976-82
references.pmid: 16940091
references.citation: Am J Transplant. 2012 Apr;12(4):984-91
references.pmid: 22225523
references.citation: Gastroenterology. 2008 May;134(6):1764-76
references.pmid: 18471553
references.citation: Transplantation. 2004 Jan 27;77(2):226-31
references.pmid: 14742986
references.citation: J Hepatol. 2001 Nov;35(5):666-78
references.pmid: 11690716
references.citation: J Virol. 2006 May;80(9):4510-20
references.pmid: 16611911
references.citation: Bone Marrow Transplant. 1997 Dec;20(11):993-5
references.pmid: 9422481