title: Daily low-dose tacrolimus is a safe and effective immunosuppressive regimen during telaprevir-based triple therapy for hepatitis C virus recurrence after liver transplant.
abstract: BACKGROUND
  Graft loss because of hepatitis C virus recurrence is a serious problem after liver transplantation (LT), and the response to pegylated interferon (PEG-IFN) and ribavirin (RBV) is poor. The significantly better response rates achieved with telaprevir (TVR)-based triple therapy have led to better graft and patient survival rates, but severe drug interactions may limit the usefulness of this therapy for LT patients. We report our single-center experience with a specially developed protocol that involved administering a low daily dose of tacrolimus (TAC) to a cohort of 17 patients with a recurrence of hepatitis C virus genotype 1 after LT.
  
  
  METHODS
  Patients were treated with TVR, PEG-IFN, and RBV for 12 weeks, followed by 12 or 36 weeks of dual therapy with PEG-IFN and RBV. After TVR administration was initiated, the TAC dosage was skipped until trough levels began to decline; it was then administered at a dose of 0.1 mg once or twice daily. Tacrolimus trough levels and laboratory values were closely monitored during the TVR phase.
  
  
  RESULTS
  Deviations in trough levels were avoided, thus preventing any clinically evident renal toxicity related to TAC. In addition, histologic studies performed at the end of therapy showed that no rejection episodes had occurred. All patients tolerated the medication. Sustained virologic response was documented for 10 of 17 patients (58%) 24 weeks after end of treatment.
  
  
  CONCLUSIONS
  In conclusion, substantial dose reduction and daily administration of low doses of TAC compose a safe and efficient immunosuppressive regimen during TVR-based triple therapy.
authors.affiliation: 1 Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany. 2 Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Essen, Germany. 3 Department of Virology, University Hospital Essen, Essen, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Papadopoulos-Köhn
authors.forename: Anne
authors.initials: A
authors.lastname: Achterfeld
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
authors.forename: Jörg
authors.initials: J
authors.lastname: Timm
authors.forename: Christoph
authors.initials: C
authors.lastname: Jochum
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005838:Genotype; D005858:Germany; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007372:Interferons / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir; D007372:Interferons; D016559:Tacrolimus