title: Telaprevir-based triple therapy in liver transplant patients with hepatitis C virus: a 12-week pilot study providing safety and efficacy data.
abstract: After liver transplantation (LT), the management of recurrent hepatitis C virus (HCV) infections still remains a major challenge. In HCV genotype 1 patients not undergoing transplantation, the introduction of protease inhibitor (PI)-based regimens has increased the sustained virological response rate significantly. This pilot study investigated both the safety and efficacy of telaprevir (TVR)-based triple therapy in HCV-infected LT patients with a special emphasis on drug-drug interactions between immunosuppressants and PIs. Safety and efficacy data were gathered for 12 weeks for 9 HCV-infected LT patients who were treated with a combination of TVR, pegylated interferon, and ribavirin (RBV) in parallel with immunosuppressive drugs such as tacrolimus (TAC; n = 4), cyclosporine A (CSA; n = 4), and sirolimus (SIR; n = 1). Seven of the transplant patients completed the 12 weeks of triple therapy. At week 4, 4 of the patients were found to be HCV RNA-negative, and importantly, 8 were found to be negative at week 12. During the 12-week course of triple therapy, short-term measurements of immunosuppressant trough levels required individual dose reductions in all patients (CSA, 2.5-fold; SIR, 7-fold; and TAC, 22-fold). Furthermore, two-thirds of the patients exhibited hematological side effects requiring RBV dose reductions, the administration of erythropoietin, or even blood transfusions. In conclusion, this pilot study provides evidence showing that TVR-based triple therapy is effective within the first 4 to 12 weeks in LT patients suffering from HCV genotype 1 recurrence, and it also provides evidence showing that drug-drug interactions between TVR and immunosuppressants can be handled appropriately through the close monitoring of trough levels and adequate dosage adjustments.
authors.affiliation: Department of Gastroenterology, Hepatology, and Infectiology, Medical Clinic, Tübingen, Germany.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Werner
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Egetemeyr
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Nisar P
authors.initials: NP
authors.lastname: Malek
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Berg
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005858:Germany; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b