PMID- 28230639
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20211204
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 102
IP  - 2S Suppl 1
DP  - 2018 Feb
TI  - mTOR Inhibition and Clinical Transplantation: Liver.
PG  - S19-S26
LID - 10.1097/TP.0000000000001690 [doi]
AB  - The evidence base concerning use of mammalian target of rapamycin (mTOR) 
      inhibitor therapy after liver transplantation is evolving rapidly, clarifying 
      their benefits and disadvantages in different clinical scenarios. The H2304 trial 
      showed that starting everolimus at 1 month posttransplant, with reduced 
      tacrolimus, achieves a sustained improvement in renal function versus standard 
      tacrolimus-based therapy, with at least equivalent immunosuppressive efficacy. 
      Randomized studies evaluating early discontinuation of calcineurin inhibitor 
      (CNI) therapy after introduction of an mTOR inhibitor consistently demonstrated a 
      substantial improvement in renal function versus standard CNI therapy. However, 
      concomitant mycophenolic acid is advisable to avoid an increase in mild 
      biopsy-proven acute rejection, and induction with an interleukin-2 receptor 
      antagonist may also be helpful. High-quality robust data regarding prevention of 
      posttransplant malignancies under mTOR inhibitors is lacking in liver 
      transplantation, although there are some indications of benefit. In maintenance 
      patients, robust data are limited regarding mTOR inhibitor initiation in response 
      to deteriorating renal function or other indications but late conversion (>1 
      year) appears ineffective. Rates of mTOR inhibitor discontinuation due to adverse 
      events are high, affecting at least a quarter of patients. In conclusion, the 
      evidence base for use of mTOR inhibitors early posttransplant to support CNI 
      reduction now convincingly demonstrates a renal advantage, but adequate 
      adjunctive immunosuppression is essential to preserve efficacy.
FAU - Nashan, Bjorn
AU  - Nashan B
AD  - Department of Hepatobiliary Surgery and Visceral Transplantation, University 
      Medical Center Eppendorf Martinistrasse, Hamburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Calcineurin Inhibitors/therapeutic use
MH  - Drug Therapy, Combination
MH  - Everolimus/*therapeutic use
MH  - Graft Rejection/*prevention & control
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - *Liver Transplantation
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Sirolimus/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Treatment Outcome
EDAT- 2017/02/24 06:00
MHDA- 2018/10/12 06:00
CRDT- 2017/02/24 06:00
PHST- 2017/02/24 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2017/02/24 06:00 [entrez]
AID - 10.1097/TP.0000000000001690 [doi]
PST - ppublish
SO  - Transplantation. 2018 Feb;102(2S Suppl 1):S19-S26. doi: 
      10.1097/TP.0000000000001690.