title: Multicenter experience using telaprevir or boceprevir with peginterferon and ribavirin to treat hepatitis C genotype 1 after liver transplantation.
abstract: The safety, efficacy, and effect on immunosuppression levels of telaprevir (TVR) or boceprevir (BOC) in combination with peginterferon (PEG-IFN) and ribavirin (RBV) in recipients of liver transplantation (LT) with hepatitis C virus (HCV) genotype 1 have not been defined. We report our 3 centers' preliminary experiences with administering triple antiviral treatment protocols containing PEG-IFN, RBV, and TVR or BOC. Patients with biopsy-proven HCV recurrence (METAVIR grade ≥ 3 and/or stage ≥ 2) received TVR with PEG-IFN/RBV for 12 weeks and then PEG-IFN/RBV for 36 weeks or BOC with PEG-IFN/RBV for 44 weeks after 4 weeks of lead-in PEG-IFN/RBV. Maintenance immunosuppression was changed to cyclosporine whenever possible, and the levels were followed closely. PEG-IFN/RBV dose adjustments were based on patients' tolerance. Sixty patients started triple antiviral treatment, and they were followed for up to 66 weeks (mean = 35 weeks); all were followed at least 12 weeks. Thirty of the 35 patients treated with TVR (86%) achieved undetectable HCV RNA levels after an average of 6 weeks, whereas 12 patients (48%) in the BOC-treated group achieved undetectable HCV RNA levels after a mean of 11 weeks. According to an intention-to-treat analysis, 14 of 21 TVR-treated patients (67%) and 10 of 22 patients who received BOC (45%) achieved undetectable HCV RNA levels at week 24 without viral breakthrough at the last follow-up. Cytopenias complicated both regimens; all patients required dose reductions of PEG-IFN and/or RBV or the administration of hematological growth factors. One death occurred in each group on triple antiviral treatment. In conclusion, TVR or BOC combined with PEG-IFN/RBV achieved on-treatment virological response rates of approximately 50% to 60% in patients with recurrent HCV after LT, but significant side effects were common.
authors.affiliation: Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA. pungpapong.surakit@mayo.edu
authors.forename: Surakit
authors.initials: S
authors.lastname: Pungpapong
authors.forename: Bashar A
authors.initials: BA
authors.lastname: Aqel
authors.forename: Ludi
authors.initials: L
authors.lastname: Koning
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Murphy
authors.forename: Tanisha M
authors.initials: TM
authors.lastname: Henry
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Ryland
authors.forename: Maria L
authors.initials: ML
authors.lastname: Yataco
authors.forename: Raj
authors.initials: R
authors.lastname: Satyanarayana
authors.forename: Barry G
authors.initials: BG
authors.lastname: Rosser
authors.forename: Hugo E
authors.initials: HE
authors.lastname: Vargas
authors.forename: Michael R
authors.initials: MR
authors.lastname: Charlton
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Keaveny
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage*; D017093:Liver Failure / Q000150:complications / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D009842:Oligopeptides; 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