title: Hepatitis C in non-hepatic solid organ transplant candidates and recipients: A new horizon.
abstract: Hepatitis C virus (HCV) infection is estimated to affect 130-150 million people globally which corresponds to 2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to non-hepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon (IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals (DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant (LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.
authors.affiliation: Sara Belga, Karen Elizabeth Doucette, Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Belga
authors.affiliation: Sara Belga, Karen Elizabeth Doucette, Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Karen Elizabeth
authors.initials: KE
authors.lastname: Doucette
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D046148:Donor Selection; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents
keywords: Antiviral agents; Chronic; Heart transplantation; Hepatitis C; Kidney failure; Kidney transplantation; Liver transplantation; Lung transplantation
references.citation: N Engl J Med. 2014 May 15;370(20):1879-88
references.pmid: 24720702
references.citation: J Gastroenterol Hepatol. 2011 Feb;26(2):228-39
references.pmid: 21261711
references.citation: J Infect Dis. 2000 Mar;181(3):852-8
references.pmid: 10720504
references.citation: Hepatology. 2015 Jul;62(1):79-86
references.pmid: 25846144
references.citation: N Engl J Med. 2014 Apr 17;370(16):1560-1
references.pmid: 24738674
references.citation: Transplant Proc. 2003 Aug;35(5):1745-7
references.pmid: 12962779
references.citation: N Engl J Med. 2014 Apr 17;370(16):1483-93
references.pmid: 24725238
references.citation: Transplant Proc. 2000 Nov;32(7):1940-3
references.pmid: 11120011
references.citation: Annu Int Conf IEEE Eng Med Biol Soc. 2014;2014:298-301
references.pmid: 25569956
references.citation: Transpl Int. 2015 Nov;28(11):1345-9
references.pmid: 26073850
references.citation: J Heart Lung Transplant. 2000 Apr;19(4):350-4
references.pmid: 10775815
references.citation: Transplantation. 2013 Mar 27;95(6):779-86
references.pmid: 23172130
references.citation: Clin Liver Dis. 2006 Nov;10(4):901-17
references.pmid: 17164124
references.citation: Am J Transplant. 2010 May;10(5):1238-46
references.pmid: 20353475
references.citation: Am J Kidney Dis. 2006 Feb;47(2):309-16
references.pmid: 16431260
references.citation: J Hepatol. 2013 Jun;58(6):1096-103
references.pmid: 23428875
references.citation: Iran J Kidney Dis. 2010 Jul;4(3):181-94
references.pmid: 20622305
references.citation: Am J Transplant. 2015 May;15(5):1313-22
references.pmid: 25708713
references.citation: Transplant Proc. 2010 Sep;42(7):2436-46
references.pmid: 20832522
references.citation: Transpl Int. 2009 Dec;22(12):1117-31
references.pmid: 19656350
references.citation: J Clin Virol. 2013 Feb;56(2):146-9
references.pmid: 23149155
references.citation: N Engl J Med. 1992 Sep 24;327(13):910-5
references.pmid: 1325035
references.citation: J Heart Lung Transplant. 1999 May;18(5):456-9
references.pmid: 10363690
references.citation: Transplantation. 2010 Dec 15;90(11):1165-71
references.pmid: 20861806
references.citation: Int J Nephrol. 2011;2011:593291
references.pmid: 21755059
references.citation: Lancet Infect Dis. 2015 Apr;15(4):397-404
references.pmid: 25773757
references.citation: Clin Transplant. 2002 Aug;16(4):243-51
references.pmid: 12099979
references.citation: J Hepatol. 2014 Feb;60(2):298-305
references.pmid: 24060854
references.citation: N Engl J Med. 2014 May 22;370(21):1993-2001
references.pmid: 24795201
references.citation: Eur Rev Med Pharmacol Sci. 2014;18(21):3174-82
references.pmid: 25487925
references.citation: J Heart Lung Transplant. 2007 May;26(5):466-71
references.pmid: 17449415
references.citation: J Heart Lung Transplant. 2001 Feb;20(2):224
references.pmid: 11250420
references.citation: Transplantation. 2002 Aug 27;74(4):427-37
references.pmid: 12352899
references.citation: Clin Microbiol Infect. 2011 Feb;17(2):107-15
references.pmid: 21091831
references.citation: Transplantation. 1996 Feb 15;61(3):378-81
references.pmid: 8610344
references.citation: Gastroenterology. 2000 Oct;119(4):1064-74
references.pmid: 11040193
references.citation: Transplant Proc. 2010 Jun;42(5):1784-7
references.pmid: 20620523
references.citation: J Viral Hepat. 2008 Aug;15(8):600-6
references.pmid: 18444984
references.citation: Transplant Proc. 2011 Apr;43(3):850-2
references.pmid: 21486613
references.citation: J Hepatol. 1995 Mar;22(3):272-7
references.pmid: 7608477
references.citation: Semin Dial. 2005 Jan-Feb;18(1):52-61
references.pmid: 15663766
references.citation: Nat Rev Nephrol. 2015 Mar;11(3):172-82
references.pmid: 25643666
references.citation: Am J Transplant. 2005 Jan;5(1):139-44
references.pmid: 15636622
references.citation: Transplant Proc. 2012 May;44(4):890-3
references.pmid: 22564576
references.citation: Liver Transpl Surg. 1999 Jul;5(4):294-300
references.pmid: 10388502
references.citation: J Am Soc Nephrol. 2002 Dec;13(12):2974-82
references.pmid: 12444217
references.citation: Am J Transplant. 2014 May;14(5):994-1002
references.pmid: 24730431
references.citation: Am J Transplant. 2005 Jul;5(7):1704-12
references.pmid: 15943629
references.citation: Kidney Int. 2004 Jun;65(6):2335-42
references.pmid: 15149347
references.citation: Am J Transplant. 2004 Dec;4(12):2032-7
references.pmid: 15575906
references.citation: Clin Gastroenterol Hepatol. 2015 Nov;13(11):1993-2001.e1-2
references.pmid: 26044317
references.citation: Clin Liver Dis. 2005 Aug;9(3):487-503, viii
references.pmid: 16023979
references.citation: Transplantation. 2007 Jun 27;83(12):1652-5
references.pmid: 17589352
references.citation: J Heart Lung Transplant. 1999 Jun;18(6):607-10
references.pmid: 10395359
references.citation: J Heart Lung Transplant. 2015 Jan;34(1):1-15
references.pmid: 25085497
references.citation: Hepatology. 2015 Jul;62(1):25-30
references.pmid: 25963890
references.citation: Clin Transplant. 2006 Nov-Dec;20(6):677-83
references.pmid: 17100715
references.citation: N Engl J Med. 2014 Apr 24;370(17):1594-603
references.pmid: 24720703
references.citation: World J Hepatol. 2015 Apr 28;7(6):885-95
references.pmid: 25937865
references.citation: Ann Thorac Surg. 2010 May;89(5):1645-7
references.pmid: 20417802
references.citation: J Hepatol. 1996 Jan;24(1):38-47
references.pmid: 8834023
references.citation: N Engl J Med. 2014 May 22;370(21):1983-92
references.pmid: 24795200
references.citation: Lancet. 1995 Feb 25;345(8948):484-7
references.pmid: 7532254
references.citation: J Am Soc Nephrol. 2011 Jun;22(6):1152-60
references.pmid: 21546575
references.citation: Drugs. 2004;64(5):489-98
references.pmid: 14977386
references.citation: Kidney Int Suppl. 2008 Apr;(109):S1-99
references.pmid: 18382440
references.citation: Transplantation. 2003 Apr 15;75(7):977-82
references.pmid: 12698083
references.citation: Transpl Int. 2009 May;22(5):562-7
references.pmid: 19175562
references.citation: Am J Kidney Dis. 2008 Feb;51(2):263-77
references.pmid: 18215704
references.citation: Hepatology. 2015 Apr;61(4):1127-35
references.pmid: 25614962
references.citation: J Heart Lung Transplant. 2004 Mar;23(3):277-83
references.pmid: 15019636
references.citation: Am J Transplant. 2013 Mar;13 Suppl 4:147-68
references.pmid: 23465008
references.citation: Transplantation. 1991 Oct;52(4):645-50
references.pmid: 1926344
references.citation: J Hepatol. 2015 Jul;63(1):199-236
references.pmid: 25911336
references.citation: Lancet. 2014 Nov 15;384(9956):1756-65
references.pmid: 25078309
references.citation: Hepatology. 1999 Jan;29(1):257-63
references.pmid: 9862875
references.citation: Dig Liver Dis. 2014 Jan;46(1):88-9
references.pmid: 24054768
references.citation: World J Gastroenterol. 2012 Jan 7;18(1):55-63
references.pmid: 22228971
references.citation: Gastroenterology. 2015 Sep;149(3):649-59
references.pmid: 25985734
references.citation: JAMA. 2006 Oct 18;296(15):1843-50
references.pmid: 17047214
references.citation: Am J Kidney Dis. 2004 Apr;43(4):685-9
references.pmid: 15042545
references.citation: J Am Soc Nephrol. 2003 Dec;14(12):3270-7
references.pmid: 14638926
references.citation: Transplantation. 2011 Jun 15;91(11):1293-6
references.pmid: 21516068
references.citation: N Engl J Med. 2013 May 16;368(20):1867-77
references.pmid: 23607593
references.citation: J Hepatol. 2011 Aug;55(2):474-82
references.pmid: 21241754
references.citation: Gastroenterology. 2015 Jan;148(1):100-107.e1
references.pmid: 25261839
references.citation: Clin Transplant. 2004 Oct;18(5):619-23
references.pmid: 15344970
references.citation: Gastroenterology. 2002 Nov;123(5):1494-9
references.pmid: 12404224
references.citation: Transplantation. 1995 Oct 27;60(8):799-805
references.pmid: 7482738
references.citation: N Engl J Med. 2014 May 15;370(20):1889-98
references.pmid: 24725239
references.citation: Hepatology. 2013 Apr;57(4):1333-42
references.pmid: 23172780
references.citation: Transplantation. 1998 Nov 15;66(9):1254-8
references.pmid: 9825826
references.citation: Can J Gastroenterol. 2011 Aug;25(8):445-8
references.pmid: 21912770
references.citation: Liver Transpl. 2009 Feb;15(2):126-35
references.pmid: 19177439
references.citation: Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34
references.pmid: 25585348
references.citation: Transplantation. 1997 Jan 15;63(1):158-60
references.pmid: 9000679
references.citation: Hepatology. 1993 Jan;17(1):5-8
references.pmid: 7678575
references.citation: Expert Opin Drug Metab Toxicol. 2013 Jan;9(1):5-16
references.pmid: 23094639
references.citation: Transplantation. 1998 Aug 27;66(4):471-6
references.pmid: 9734490
references.citation: J Am Soc Nephrol. 2003 Nov;14(11):2908-18
references.pmid: 14569101
references.citation: Transplantation. 2010 Jul 15;90(1):61-7
references.pmid: 20463638
references.citation: Am J Gastroenterol. 2008 Aug;103(8):2123-34
references.pmid: 18796105
references.citation: Transplantation. 1998 Mar 15;65(5):667-70
references.pmid: 9521201