PMID- 25214801
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140912
LR  - 20211021
IS  - 1178-7023 (Print)
IS  - 1178-7023 (Electronic)
IS  - 1178-7023 (Linking)
VI  - 7
DP  - 2014
TI  - The role of everolimus in liver transplantation.
PG  - 329-43
LID - 10.2147/CEG.S41780 [doi]
AB  - During the last 5 decades, liver transplantation has witnessed rapid development 
      in terms of both technical and pharmacologic advances. Since their discovery, 
      calcineurin inhibitors (CNIs) have remained the standard of care for 
      immunosuppression therapy in liver transplantation, improving both patient and 
      graft survival. However, adverse events, particularly posttransplant 
      nephrotoxicity, associated with long-term CNI use have necessitated the 
      development of alternate treatment approaches. These include combination therapy 
      with a CNI and the inosine monophosphate dehydrogenase inhibitor mycophenolic 
      acid and use of mammalian target of rapamycin (mTOR) inhibitors. Everolimus, a 
      40-O-(2-hydroxyethyl) derivative of mTOR inhibitor sirolimus, has a distinct 
      pharmacokinetic profile. Several studies have assessed the role of everolimus in 
      liver transplant recipients in combination with CNI reduction or as a CNI 
      withdrawal strategy. The efficacy of everolimus-based immunosuppressive therapy 
      has been demonstrated in both de novo and maintenance liver transplant 
      recipients. A pivotal study in 719 de novo liver transplant recipients formed the 
      basis of the recent approval of everolimus in combination with steroids and 
      reduced-dose tacrolimus in liver transplantation. In this study, everolimus 
      introduced at 30 days posttransplantation in combination with reduced-dose 
      tacrolimus (exposure reduced by 39%) showed comparable efficacy (composite 
      efficacy failure rate of treated biopsy-proven acute rejection, graft loss, or 
      death) and achieved superior renal function as early as month 1 and maintained it 
      over 2 years versus standard exposure tacrolimus. This review provides an 
      overview of the efficacy and safety of everolimus-based regimens in liver 
      transplantation in the de novo and maintenance settings, as well as in special 
      populations such as patients with hepatocellular carcinoma recurrence, hepatitis 
      C virus-positive patients, and pediatric transplant recipients. We also provide 
      an overview of ongoing studies and discuss potential expansion of the role for 
      everolimus in these settings.
FAU - Ganschow, Rainer
AU  - Ganschow R
AD  - Department of Pediatrics, University of Bonn, Bonn, Germany.
FAU - Pollok, Jorg-Matthias
AU  - Pollok JM
AD  - Department of General, Visceral, Thoracic, and Vascular Surgery, University of 
      Bonn, Bonn, Germany.
FAU - Jankofsky, Martin
AU  - Jankofsky M
AD  - Department of Pediatrics, University of Bonn, Bonn, Germany.
FAU - Junge, Guido
AU  - Junge G
AD  - Integrated Hospital Care, Novartis Pharma AG, Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140902
PL  - New Zealand
TA  - Clin Exp Gastroenterol
JT  - Clinical and experimental gastroenterology
JID - 101532800
PMC - PMC4159129
OTO - NOTNLM
OT  - efficacy
OT  - everolimus
OT  - liver transplantation
OT  - mTOR inhibitors
OT  - safety
EDAT- 2014/09/13 06:00
MHDA- 2014/09/13 06:01
PMCR- 2014/09/02
CRDT- 2014/09/13 06:00
PHST- 2014/09/13 06:00 [entrez]
PHST- 2014/09/13 06:00 [pubmed]
PHST- 2014/09/13 06:01 [medline]
PHST- 2014/09/02 00:00 [pmc-release]
AID - ceg-7-329 [pii]
AID - 10.2147/CEG.S41780 [doi]
PST - epublish
SO  - Clin Exp Gastroenterol. 2014 Sep 2;7:329-43. doi: 10.2147/CEG.S41780. eCollection 
      2014.