title: Current strategies for immunosuppression following liver transplantation.
abstract: BACKGROUND
  New strategies for immunosuppression (IS) after liver transplantation (LTx) are in part responsible for the increased patient and graft survival seen over time. With a few basic exceptions-notably the continued use of steroids and calcineurin inhibitors (CNIs)-IS drugs and regimens being used today are different from those used 30 years ago. While graft loss due to acute or chronic rejection has become rare, the side effect burden of IS drugs exerts a significant toll on patients.
  CNIs continue to form the backbone of IS regimens, although their use is hampered by nephrotoxicity and other adverse effects. Consequently, a variety of CNI reduction or withdrawal strategies have formed the basis of clinical trials or entered into clinical practice. These trials have included the use of everolimus, an mTOR inhibitor, and anti-interleukin-2 receptor antibodies. Basiliximab, as well as other lymphocyte nondepleting and depleting agents, have shown benefit in induction regimens.
  
  
  CONCLUSIONS
  Along with steroid reduction or elimination, current strategies for IS after LTx continue to explore novel combinations of agents, with an aim toward striking a balance between diminution of rejection and the need for avoiding adverse effects of the IS drugs. Long-term maintenance strategies are also discussed in this review, as is development of tolerance and antibody-mediated rejection.
authors.affiliation: Department of Internal Medicine IV, University Hospital of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany, daniel_gotthardt@med.uni-heidelberg.de.
authors.forename: Daniel Nils
authors.initials: DN
authors.lastname: Gotthardt
authors.forename: Helge
authors.initials: H
authors.lastname: Bruns
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Weiss
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
mesh_terms: D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation
chemical_list: D007166:Immunosuppressive Agents
references.citation: Cancer Med. 2013 Dec;2(6):862-71
references.pmid: 24403259
references.citation: Liver Transpl. 2013 Jul;19(7):675-89
references.pmid: 23775875
references.citation: JAMA. 2012 Jan 18;307(3):283-93
references.pmid: 22253395
references.citation: Am J Transplant. 2010 Oct;10(10):2313-23
references.pmid: 20840481
references.citation: Cochrane Database Syst Rev. 2012 Mar 14;(3):CD008852
references.pmid: 22419339
references.citation: Liver Transpl. 2003 Dec;9(12):1231-43
references.pmid: 14625822
references.citation: Liver Transpl. 2012 Jul;18(7):786-95
references.pmid: 22237953
references.citation: Transpl Int. 2009 Sep;22(9):892-905
references.pmid: 19453997
references.citation: Liver Transpl. 2011 Dec;17(12):1394-403
references.pmid: 21850690
references.citation: Transplant Proc. 2010 May;42(4):1237-9
references.pmid: 20534270
references.citation: Liver Int. 2013 May;33(5):656-65
references.pmid: 23442173
references.citation: Am J Transplant. 2012 Nov;12(11):3047-60
references.pmid: 22947059
references.citation: PLoS One. 2013 Aug 06;8(8):e71251
references.pmid: 23940730
references.citation: J Hepatol. 2013 Feb;58(2):262-70
references.pmid: 23023010
references.citation: J Hepatol. 2013 Oct;59(4):872-9
references.pmid: 23578883
references.citation: Langenbecks Arch Surg. 2007 Sep;392(5):511-23
references.pmid: 17450373
references.citation: Transpl Int. 2013 Jun;26(6):576-89
references.pmid: 23517251
references.citation: Am J Transplant. 2014 Mar;14(3):701-10
references.pmid: 24502384
references.citation: Transpl Int. 2013 Jul;26(7):673-83
references.pmid: 23651083
references.citation: Am J Transplant. 2012 Nov;12(11):3008-20
references.pmid: 22882750
references.citation: Liver Transpl. 2011 Nov;17 Suppl 3:S66-8
references.pmid: 21748844
references.citation: J Am Coll Surg. 2012 Feb;214(2):164-73
references.pmid: 22137824
references.citation: Am J Transplant. 2007 Jun;7(6):1609-15
references.pmid: 17511684
references.citation: Am J Transplant. 2012 Mar;12(3):694-705
references.pmid: 22233522
references.citation: Liver Transpl. 2007 Jan;13(1):46-54
references.pmid: 17154392
references.citation: Am J Transplant. 2013 Jul;13(7):1734-45
references.pmid: 23714399
references.citation: Z Gastroenterol. 2011 Jan;49(1):30-8
references.pmid: 21225535
references.citation: Ann Surg. 2008 Dec;248(6):956-67
references.pmid: 19092340
references.citation: Gut. 2009 Mar;58(3):452-63
references.pmid: 19052024
references.citation: Liver Transpl. 2009 Oct;15(10):1262-9
references.pmid: 19790150
references.citation: Am J Transplant. 2013 May;13(5):1371-2
references.pmid: 23621166
references.citation: Liver Transpl. 2011 Jan;17(1):32-7
references.pmid: 21254342
references.citation: Am J Transplant. 2010 Oct;10(10):2252-62
references.pmid: 20486905
references.citation: Liver Transpl. 2002 Feb;8(2):123-31
references.pmid: 11862588
references.citation: J Hepatol. 2013 Dec;59(6):1223-30
references.pmid: 23933266
references.citation: Liver Transpl. 2007 Jul;13(7):1004-10
references.pmid: 17600361
references.citation: Am J Transplant. 2012 Jul;12(7):1855-65
references.pmid: 22494671
references.citation: Ann Surg. 1968 Sep;168(3):392-415
references.pmid: 4877589
references.citation: Am J Transplant. 2013 Sep;13(9):2384-94
references.pmid: 23915357
references.citation: Transplantation. 2011 Jun 15;91(11):1254-60
references.pmid: 21617588
references.citation: Am J Transplant. 2011 May;11(5):965-76
references.pmid: 21466650
references.citation: Liver Transpl. 2005 Jul;11(7):750-759
references.pmid: 15973716
references.citation: Clin Transplant. 2011 Jul-Aug;25(4):660-9
references.pmid: 21158921
references.citation: Am J Transplant. 2012 Sep;12(9):2526-31
references.pmid: 22681986
references.citation: Liver Transpl. 2013 Sep;19(9):937-44
references.pmid: 23784747
references.citation: Liver Transpl. 2011 Nov;17 Suppl 3:S69-73
references.pmid: 21850680
references.citation: Transpl Int. 2009 Mar;22(3):279-86
references.pmid: 19054383
references.citation: Liver Transpl. 2013 May;19(5):529-33
references.pmid: 23483701
references.citation: Liver Transpl. 2011 Nov;17 Suppl 3:S1-9
references.pmid: 21850697
references.citation: Transplantation. 2010 Dec 27;90(12):1511-5
references.pmid: 21057388
references.citation: Transplantation. 2011 Oct 27;92(8):923-9
references.pmid: 21832958
references.citation: N Engl J Med. 2012 Oct 18;367(16):1483-5
references.pmid: 22992048
references.citation: Gut. 2014 Jun;63(6):1005-13
references.pmid: 24131637
references.citation: Transpl Int. 2011 Jan;24(1):91-9
references.pmid: 20819196
references.citation: Transplantation. 2010 Dec 27;90(12):1562-6
references.pmid: 21048536
references.citation: Ann Surg. 2000 Oct;232(4):490-500
references.pmid: 10998647
references.citation: Hepatology. 2013 Nov;58(5):1824-35
references.pmid: 23532679
references.citation: Liver Transpl. 2011 Aug;17(8):905-13
references.pmid: 21384525
references.citation: Best Pract Res Clin Gastroenterol. 2012 Feb;26(1):73-84
references.pmid: 22482527
references.citation: Am J Transplant. 2012 Oct;12(10):2797-814
references.pmid: 22703529
references.citation: Liver Transpl. 2002 Feb;8(2):132-42
references.pmid: 11862589
references.citation: Am J Transplant. 2007 Jun;7(6):1616-23
references.pmid: 17511685
references.citation: Clin Transplant. 2013 May-Jun;27(3):463-71
references.pmid: 23621629
references.citation: Liver Transpl. 2008 Apr;14(4):512-25
references.pmid: 18383081
references.citation: Am J Transplant. 2007 Feb;7(2):309-19
references.pmid: 17241111