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Risks and Epidemiology of Infections After Liver Transplantation

Chapter

Abstract

Liver transplant recipients have a high risk of infectious complications, compared with recipients of other solid organs, despite the improvement in surgical techniques, shortening of operative times, and the development of novel anti-infective agents in the last decade. A careful examination of risk factors, diligent surveillance for early signs of infection, and prompt intervention are necessary to minimize serious infectious complications, which often contribute to graft loss and death in this population. Future strategies to develop diagnostic assays that are rapid, cost-effective, standardized, and easily performed will improve our abilities to prevent donor-transmitted infections. Ability to assess the immune competence of the recipients and to optimally prescribe appropriate antimicrobial prophylaxis will allow us to prevent infection. Areas such as liver transplant in HIV coinfection and the prevention of recurrence of viral hepatitides after transplantation have made some progress but require further research before the establishment of accepted therapeutic strategies.

Keywords

Liver transplantation Infections Immunosuppression Viral Bacterial Fungal Transmission 

Notes

Acknowledgment.

We would like to acknowledge the help of Dr. E. J. Kwak from University of Pittsburgh Medical Center who assisted in writing the previous edition of this chapter.

References

  1. 1.
    Kusne S, et al. Infections after liver transplantation. An analysis of 101 consecutive cases. Medicine (Baltimore). 1988;67(2):132–43.CrossRefGoogle Scholar
  2. 2.
    Paya CV, et al. Incidence, distribution, and outcome of episodes of infection in 100 orthotopic liver transplantations. Mayo Clin Proc. 1989;64(5):555–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Hadley S, et al. Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression. Transplantation. 1995;59(6):851–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Asensio A, et al. Effect of antibiotic prophylaxis on the risk of surgical site infection in orthotopic liver transplant. Liver Transpl. 2008;14(6):799–805.PubMedCrossRefGoogle Scholar
  5. 5.
    Shepherd RW, et al. Risk factors for rejection and infection in pediatric liver transplantation. Am J Transplant. 2008;8(2):396–403.PubMedCrossRefGoogle Scholar
  6. 6.
    Dummer JS, et al. Early infections in kidney, heart, and liver transplant recipients on cyclosporine. Transplantation. 1983;36(3):259–67.PubMedCrossRefGoogle Scholar
  7. 7.
    Kusne S, et al. Infectious complications after small bowel transplantation in adults: an update. Transplant Proc. 1996;28(5):2761–2.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Horvath J, et al. Infection in the transplanted and native lung after single lung transplantation. Chest. 1993;104(3):681–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Freeman RB, Cohen JT. Transplantation risks and the real world: what does ‘high risk’ really mean? Am J Transplant. 2009;9(1):23–30.PubMedCrossRefGoogle Scholar
  10. 10.
    UNOS/OPTN, Donor National Data.Google Scholar
  11. 11.
    George DL, et al. Bacterial infection as a complication of liver transplantation: epidemiology and risk factors. Rev Infect Dis. 1991;13(3):387–96.PubMedCrossRefGoogle Scholar
  12. 12.
    Dummer S, Kusne S. Liver transplantation and related infections. Semin Respir Infect. 1993;8(3):191–8.PubMedGoogle Scholar
  13. 13.
    Collins LA, et al. Risk factors for invasive fungal infections complicating orthotopic liver transplantation. J Infect Dis. 1994;170(3):644–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Castaldo P, et al. Clinical spectrum of fungal infections after orthotopic liver transplantation. Arch Surg. 1991;126(2):149–56.PubMedCrossRefGoogle Scholar
  15. 15.
    Tollemar J, et al. The incidence and diagnosis of invasive fungal infections in liver transplant recipients. Transplant Proc. 1990;22(1):242–4.PubMedGoogle Scholar
  16. 16.
    Wajszczuk CP, et al. Fungal infections in liver transplant recipients. Transplantation. 1985;40(4):347–53.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Lebeau G, et al. Analysis of surgical complications after 397 hepatic transplantations. Surg Gynecol Obstet. 1990;170(4):317–22.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Hau T, Hoffman R, Simmons RL. Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. I. In vivo inhibition of peritoneal leukocytosis. Surgery. 1978;83(2):223–9.PubMedGoogle Scholar
  19. 19.
    Vamvakas EC, Blajchman MA. Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction? Blood. 2001;97(5):1180–95.PubMedCrossRefGoogle Scholar
  20. 20.
    Bubak ME, et al. Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy. Hepatology. 1991;14(6):1063–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Rolles K, et al. Biliary anastomosis after liver transplantation does not benefit from T tube splintage. Transplantation. 1994;57(3):402–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Koivusalo A, et al. Biliary complications in 100 adult liver transplantations: a retrospective clinical study. Transpl Int. 1994;7 Suppl 1:S119–20.PubMedCrossRefGoogle Scholar
  23. 23.
    Jeffrey GP, et al. Management of biliary tract complications following liver transplantation. Aust N Z J Surg. 1999;69(10):717–22.PubMedCrossRefGoogle Scholar
  24. 24.
    Rabkin JM, et al. Hepatic allograft abscess with hepatic arterial thrombosis. Am J Surg. 1998;175(5):354–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Kaplan SB, Zajko AB, Koneru B. Hepatic bilomas due to hepatic artery thrombosis in liver transplant recipients: percutaneous drainage and clinical outcome. Radiology. 1990;174(3 Pt 2):1031–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Tzakis AG, et al. Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era. Transplantation. 1985;40(6):667–71.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Castiglioni B, Daly I, Linden P, et al. Diagnosis and management of liver abscess secondary to vascular complications in adult liver transplant recipients [abstract 62]. In: Program and abstracts of the annual meeting of the infectious diseases society of America; 2001.Google Scholar
  28. 28.
    Tachopoulou OA, et al. Hepatic abscess after liver transplantation: 1990-2000. Transplantation. 2003;75(1):79–83.PubMedCrossRefGoogle Scholar
  29. 29.
    Safdar N, et al. Infected bilomas in liver transplant recipients: clinical features, optimal management, and risk factors for mortality. Clin Infect Dis. 2004;39(4):517–25.PubMedCrossRefGoogle Scholar
  30. 30.
    Samuel D, et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med. 1993;329(25):1842–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Terrault NA, Wright TL, Pereira BJ. Hepatitis C infection in the transplant recipient. Infect Dis Clin North Am. 1995;9(4):943–64.PubMedGoogle Scholar
  32. 32.
    Nieto-Rodriguez JA, et al. Factors associated with the development of candidemia and candidemia-related death among liver transplant recipients. Ann Surg. 1996;223(1):70–6.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Singh N, et al. Predicting bacteremia and bacteremic mortality in liver transplant recipients. Liver Transpl. 2000;6(1):54–61.PubMedGoogle Scholar
  34. 34.
    Brandhagen DJ, et al. Iron overload in cirrhosis-HFE genotypes and outcome after liver transplantation. Hepatology. 2000;31(2):456–60.PubMedCrossRefGoogle Scholar
  35. 35.
    Alexander J, et al. Association of hepatic iron overload with invasive fungal infection in liver transplant recipients. Liver Transpl. 2006;12(12):1799–804.PubMedCrossRefGoogle Scholar
  36. 36.
    Kusne S, et al. Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation. J Infect Dis. 1992;166(6):1379–83.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Cavusoglu C, et al. Mycobacterium tuberculosis infection and laboratory diagnosis in solid-organ transplant recipients. Clin Transplant. 2002;16(4):257–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Jha V, Chugh KS. Posttransplant infections in the tropical countries. Artif Organs. 2002;26(9):770–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Nierenberg NE, et al. Pretransplant lymphopenia is a novel prognostic factor in cytomegalovirus and noncytomegalovirus invasive infections after liver transplantation. Liver Transpl. 2014;20(12):1497–507.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Tzakis AG, et al. Transplantation in HIV+ patients. Transplantation. 1990;49(2):354–8.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Bouscarat F, et al. An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1. Clin Infect Dis. 1994;19(5):854–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Gow PJ, Pillay D, Mutimer D. Solid organ transplantation in patients with HIV infection. Transplantation. 2001;72(2):177–81.PubMedCrossRefGoogle Scholar
  43. 43.
    Fung J, et al. Liver transplantation in patients with HIV infection. Liver Transpl. 2004;10(10 Suppl 2):S39–53.PubMedCrossRefGoogle Scholar
  44. 44.
    Stock PG, Roland ME. Evolving clinical strategies for transplantation in the HIV-positive recipient. Transplantation. 2007;84(5):563–71.PubMedCrossRefGoogle Scholar
  45. 45.
    Teicher E, et al. Infectious complications after liver transplantation in human immunodeficiency virus-infected recipients. Transpl Infect Dis. 2015;17(5):662–70.PubMedCrossRefGoogle Scholar
  46. 46.
    Locke JE, et al. Long-term outcomes after liver transplantation among human immunodeficiency virus-infected recipients. Transplantation. 2015;100(1):141–6.CrossRefGoogle Scholar
  47. 47.
    Taylor AL, Watson CJ, Bradley JA. Immunosuppressive agents in solid organ transplantation: mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol. 2005;56(1):23–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transpl Int. 2006;19(9):705–14.PubMedCrossRefGoogle Scholar
  49. 49.
    Kusne S, et al. Infections during a randomized trial comparing cyclosporine to FK 506 immunosuppression in liver transplantation. Transplant Proc. 1992;24(1):429–30.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Paterson DL, et al. Infectious complications occurring in liver transplant recipients receiving mycophenolate mofetil. Transplantation. 1998;66(5):593–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Fisher A, et al. Effect of sirolimus on infection incidence in liver transplant recipients. Liver Transpl. 2004;10(2):193–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Singh N, et al. Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies. J Infect Dis. 1988;158(1):124–31.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Paya CV, et al. Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: a prospective multivariate time-dependent analysis. J Hepatol. 1993;18(2):185–95.PubMedCrossRefGoogle Scholar
  54. 54.
    Swinnen LJ, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med. 1990;323(25):1723–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Peleg AY, et al. Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody. Clin Infect Dis. 2007;44(2):204–12.PubMedCrossRefGoogle Scholar
  56. 56.
    Lumbreras C, et al. Major bacterial infections following liver transplantation: a prospective study. Hepatogastroenterology. 1992;39(4):362–5.PubMedGoogle Scholar
  57. 57.
    Garcia S, et al. Infection and associated risk factors in the immediate postoperative period of pediatric liver transplantation: a study of 176 transplants. Clin Transplant. 1998;12(3):190–7.PubMedGoogle Scholar
  58. 58.
    Ziakas PD, et al. MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies. Am J Transplant. 2014;14(8):1887–94.PubMedCrossRefGoogle Scholar
  59. 59.
    Schweizer ML, et al. Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery. JAMA. 2015;313(21):2162–71.PubMedCrossRefGoogle Scholar
  60. 60.
    Desai D, et al. Carriage of methicillin-resistant Staphylococcus aureus is associated with an increased risk of infection after liver transplantation. Liver Transpl. 2003;9(7):754–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Bert F, et al. Association between nasal carriage of Staphylococcus aureus and infection in liver transplant recipients. Clin Infect Dis. 2000;31(5):1295–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Singh N, et al. Methicillin-resistant Staphylococcus aureus: the other emerging resistant gram-positive coccus among liver transplant recipients. Clin Infect Dis. 2000;30(2):322–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Singh N, et al. Impact of an aggressive infection control strategy on endemic Staphylococcus aureus infection in liver transplant recipients. Infect Control Hosp Epidemiol. 2006;27(2):122–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Bakir M, et al. Epidemiology and clinical consequences of vancomycin-resistant enterococci in liver transplant patients. Transplantation. 2001;72(6):1032–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Singh N, et al. Evolving trends in multiple-antibiotic-resistant bacteria in liver transplant recipients: a longitudinal study of antimicrobial susceptibility patterns. Liver Transpl. 2001;7(1):22–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Linden PK, et al. Differences in outcomes for patients with bacteremia due to vancomycin-resistant Enterococcus faecium or vancomycin-susceptible E. faecium. Clin Infect Dis. 1996;22(4):663–70.PubMedCrossRefGoogle Scholar
  67. 67.
    Pelz RK, et al. Vancomycin-sensitive and vancomycin-resistant enterococcal infections in the ICU: attributable costs and outcomes. Intensive Care Med. 2002;28(6):692–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Herrero IA, Issa NC, Patel R. Nosocomial spread of linezolid-resistant, vancomycin-resistant Enterococcus faecium. N Engl J Med. 2002;346(11):867–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Kalpoe JS, et al. Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients. Liver Transpl. 2012;18(4):468–74.PubMedCrossRefGoogle Scholar
  70. 70.
    Bodro M, et al. Risk factors and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in solid-organ transplant recipients. Transplantation. 2013;96(9):843–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Pereira MR, et al. Risk factors and outcomes of carbapenem-resistant klebsiella pneumoniae infections in liver transplant recipients. Liver Transpl. 2015;21(12):1511–9.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Colonna 2nd JO, et al. Infectious complications in liver transplantation. Arch Surg. 1988;123(3):360–4.PubMedCrossRefGoogle Scholar
  73. 73.
    Schelenz S, French G. An outbreak of multidrug-resistant Pseudomonas aeruginosa infection associated with contamination of bronchoscopes and an endoscope washer-disinfector. J Hosp Infect. 2000;46(1):23–30.PubMedCrossRefGoogle Scholar
  74. 74.
    Stout JE, Yu VL. Legionellosis. N Engl J Med. 1997;337(10):682–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Barbut F, Petit JC. Epidemiology of Clostridium difficile-associated infections. Clin Microbiol Infect. 2001;7(8):405–10.PubMedCrossRefGoogle Scholar
  76. 76.
    McDonald LC, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353(23):2433–41.PubMedCrossRefGoogle Scholar
  77. 77.
    Pant C, et al. Association of Clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: results from the 2009 Nationwide Inpatient Sample database. Transpl Infect Dis. 2012;14(5):540–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Bratzler DW, et al. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004;38(12):1706–15.PubMedCrossRefGoogle Scholar
  79. 79.
    Wiesner RH, et al. Selective bowel decontamination to decrease gram-negative aerobic bacterial and Candida colonization and prevent infection after orthotopic liver transplantation. Transplantation. 1988;45(3):570–4.PubMedCrossRefGoogle Scholar
  80. 80.
    Arnow PM, et al. Randomized controlled trial of selective bowel decontamination for prevention of infections following liver transplantation. Clin Infect Dis. 1996;22(6):997–1003.PubMedCrossRefGoogle Scholar
  81. 81.
    Hjortrup A, et al. Early bacterial and fungal infections in liver transplantation after oral selective bowel decontamination. Transplant Proc. 1997;29(7):3106–10.PubMedCrossRefGoogle Scholar
  82. 82.
    Kuo PC, et al. Selective bowel decontamination in hospitalized patients awaiting liver transplantation. Am J Surg. 1997;174(6):745–8. discussion 749.PubMedCrossRefGoogle Scholar
  83. 83.
    Hellinger WC, et al. A randomized, prospective, double-blinded evaluation of selective bowel decontamination in liver transplantation. Transplantation. 2002;73(12):1904–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Patel R, et al. Risk factors of invasive Candida and non-Candida fungal infections after liver transplantation. Transplantation. 1996;62(7):926–34.PubMedCrossRefGoogle Scholar
  85. 85.
    George MJ, et al. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med. 1997;103(2):106–13.PubMedCrossRefGoogle Scholar
  86. 86.
    Briegel J, et al. Risk factors for systemic fungal infections in liver transplant recipients. Eur J Clin Microbiol Infect Dis. 1995;14(5):375–82.PubMedCrossRefGoogle Scholar
  87. 87.
    Vilchez RA, Fung J, Kusne S. Cryptococcosis in organ transplant recipients: an overview. Am J Transplant. 2002;2(7):575–80.PubMedCrossRefGoogle Scholar
  88. 88.
    Paya CV. Prevention of fungal and hepatitis virus infections in liver transplantation. Clin Infect Dis. 2001;33 Suppl 1:S47–52.PubMedCrossRefGoogle Scholar
  89. 89.
    Kusne S, et al. Candida carriage in the alimentary tract of liver transplant candidates. Transplantation. 1994;57(3):398–402.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Cohen R, et al. Fungal flora of the normal human small and large intestine. N Engl J Med. 1969;280(12):638–41.PubMedCrossRefGoogle Scholar
  91. 91.
    Kullberg BJ, Oude Lashof AM. Epidemiology of opportunistic invasive mycoses. Eur J Med Res. 2002;7(5):183–91.PubMedGoogle Scholar
  92. 92.
    Husain S, et al. Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study. Transplantation. 2003;75(12):2023–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Eschenauer GA, Nguyen MH, Clancy CJ. Is fluconazole or an echinocandin the agent of choice for candidemia. Ann Pharmacother. 2015;49(9):1068–74.PubMedCrossRefGoogle Scholar
  94. 94.
    Mora-Duarte J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Rex JH, et al. Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30(4):662–78.PubMedCrossRefGoogle Scholar
  96. 96.
    Duchini A, et al. Aspergillosis in liver transplant recipients: successful treatment and improved survival using a multistep approach. South Med J. 2002;95(8):897–9.PubMedGoogle Scholar
  97. 97.
    Linden PK, et al. Invasive aspergillosis in liver transplant recipients: outcome comparison of therapy with amphotericin B lipid complex and a historical cohort treated with conventional amphotericin B. Clin Infect Dis. 2003;37(1):17–25.PubMedCrossRefGoogle Scholar
  98. 98.
    Herbrecht R, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15.PubMedCrossRefGoogle Scholar
  99. 99.
    Walsh TJ, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.PubMedCrossRefGoogle Scholar
  100. 100.
    Siopi M, et al. Optimization of polyene-azole combination therapy against aspergillosis using an in vitro pharmacokinetic-pharmacodynamic model. Antimicrob Agents Chemother. 2015;59(7):3973–83.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Marr KA, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162(2):81–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Fuhren, J, et al. High prevalence of azole resistance in Aspergillus fumigatus isolates from high-risk patients. J Antimicrob Chemother. 2015;70(10):2894–8Google Scholar
  103. 103.
    Miceli MH, Kauffman CA. Isavuconazole: a new broad-spectrum triazole antifungal agent. Clin Infect Dis. 2015;61(10):1558–65.PubMedCrossRefGoogle Scholar
  104. 104.
    Jabbour N, et al. Cryptococcal meningitis after liver transplantation. Transplantation. 1996;61(1):146–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg Infect Dis. 2001;7(3):375–81.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Vilchez RA, et al. The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center. Medicine (Baltimore). 2001;80(5):308–12.CrossRefGoogle Scholar
  107. 107.
    Wu G, et al. Cryptococcal meningitis: an analysis among 5,521 consecutive organ transplant recipients. Transpl Infect Dis. 2002;4(4):183–8.PubMedCrossRefGoogle Scholar
  108. 108.
    Perfect JR, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291–322.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Centers for Disease, Control and Prevention. Emergence of Cryptococcus gattii—Pacific Northwest, 2004-2010. Morb Mortal Wkly Rep. 2010;59(28):865–8.Google Scholar
  110. 110.
    Forrest GN, et al. Cryptococcus gattii infection in solid organ transplant recipients: description of Oregon outbreak cases. Transpl Infect Dis. 2015;17(3):467–76.PubMedCrossRefGoogle Scholar
  111. 111.
    Lumbreras C, et al. Randomized trial of fluconazole versus nystatin for the prophylaxis of Candida infection following liver transplantation. J Infect Dis. 1996;174(3):583–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Winston DJ, Pakrasi A, Busuttil RW. Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131(10):729–37.PubMedCrossRefGoogle Scholar
  113. 113.
    Tollemar J, et al. Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study. Transplantation. 1995;59(1):45–50.PubMedCrossRefGoogle Scholar
  114. 114.
    Fortun J, et al. Selection of Candida glabrata strains with reduced susceptibility to azoles in four liver transplant patients with invasive candidiasis. Eur J Clin Microbiol Infect Dis. 1997;16(4):314–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Fortun J, et al. Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients. J Antimicrob Chemother. 2003;52(5):813–9.PubMedCrossRefGoogle Scholar
  116. 116.
    Hellinger WC, et al. Risk stratification and targeted antifungal prophylaxis for prevention of aspergillosis and other invasive mold infections after liver transplantation. Liver Transpl. 2005;11(6):656–62.PubMedCrossRefGoogle Scholar
  117. 117.
    Paya CV, et al. Cytomegalovirus hepatitis in liver transplantation: prospective analysis of 93 consecutive orthotopic liver transplantations. J Infect Dis. 1989;160(5):752–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Badley AD, et al. Prognostic significance and risk factors of untreated cytomegalovirus viremia in liver transplant recipients. J Infect Dis. 1996;173(2):446–9.PubMedCrossRefGoogle Scholar
  119. 119.
    Portela D, et al. OKT3 treatment for allograft rejection is a risk factor for cytomegalovirus disease in liver transplantation. J Infect Dis. 1995;171(4):1014–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Dummer JS, et al. The effect of cytomegalovirus and Epstein-Barr virus infection on T lymphocyte subsets in cardiac transplant patients on cyclosporine. Transplantation. 1984;38(4):433–5.PubMedCrossRefGoogle Scholar
  121. 121.
    Maher P, et al. Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ TS-C+ subset. Clin Exp Immunol. 1985;62(3):515–24.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Saliba F, et al. Randomized controlled trial of acyclovir for the prevention of cytomegalovirus infection and disease in liver transplant recipients. Transplant Proc. 1993;25(1 Pt 2):1444–5.PubMedGoogle Scholar
  123. 123.
    Winston DJ, et al. Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients. Lancet. 1995;346(8967):69–74.PubMedCrossRefGoogle Scholar
  124. 124.
    Paya CV, et al. Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial. J Infect Dis. 2002;185(7):854–60.PubMedCrossRefGoogle Scholar
  125. 125.
    Badley AD, et al. Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database. Transplantation. 1997;64(1):66–73.PubMedCrossRefGoogle Scholar
  126. 126.
    Singh N, et al. Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial. Transplantation. 2000;70(5):717–22.PubMedCrossRefGoogle Scholar
  127. 127.
    Green M, et al. Comparison of intravenous ganciclovir followed by oral acyclovir with intravenous ganciclovir alone for prevention of cytomegalovirus and Epstein-Barr virus disease after liver transplantation in children. Clin Infect Dis. 1997;25(6):1344–9.PubMedCrossRefGoogle Scholar
  128. 128.
    Singh N, et al. High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial. Ann Intern Med. 1994;120(5):375–81.PubMedCrossRefGoogle Scholar
  129. 129.
    Gane E, et al. Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected]. Lancet. 1997;350(9093):1729–33.PubMedCrossRefGoogle Scholar
  130. 130.
    Pescovitz MD, et al. Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother. 2000;44(10):2811–5.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Paya C, et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004;4(4):611–20.PubMedCrossRefGoogle Scholar
  132. 132.
    Cytomegalovirus. Am J Transplant. 2004;4 Suppl 10:51–8.Google Scholar
  133. 133.
    Limaye AP, et al. Late-onset cytomegalovirus disease in liver transplant recipients despite antiviral prophylaxis. Transplantation. 2004;78(9):1390–6.PubMedCrossRefGoogle Scholar
  134. 134.
    Singh N, et al. Late onset cytomegalovirus disease in liver transplant recipients: de novo reactivation in recurrent hepatitis C virus hepatitis. Transpl Int. 1998;11(4):308–11.PubMedCrossRefGoogle Scholar
  135. 135.
    Marty FM, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–36.PubMedCrossRefGoogle Scholar
  136. 136.
    Stoelben S, et al. Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a Phase 2a study. Transpl Int. 2014;27(1):77–86.PubMedCrossRefGoogle Scholar
  137. 137.
    Chemaly RF, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781–9.PubMedCrossRefGoogle Scholar
  138. 138.
    Chon WJ, et al. Use of leflunomide in renal transplant recipients with ganciclovir-resistant/refractory cytomegalovirus infection: a case series from the University of Chicago. Case Rep Nephrol Dial. 2015;5(1):96–105.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Winston DJ, et al. Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial. Am J Transplant. 2012;12(11):3021–30.PubMedCrossRefGoogle Scholar
  140. 140.
    Kusne S, et al. Herpes simplex virus hepatitis after solid organ transplantation in adults. J Infect Dis. 1991;163(5):1001–7.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Breinig MK, et al. Epstein-Barr virus, cytomegalovirus, and other viral infections in children after liver transplantation. J Infect Dis. 1987;156(2):273–9.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Gold D, Corey L. Acyclovir prophylaxis for herpes simplex virus infection. Antimicrob Agents Chemother. 1987;31(3):361–7.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Slifkin M, Doron S, Snydman DR. Viral prophylaxis in organ transplant patients. Drugs. 2004;64(24):2763–92.PubMedCrossRefGoogle Scholar
  144. 144.
    Saad RS, et al. Adenovirus hepatitis in the adult allograft liver. Transplantation. 1997;64(10):1483–5.PubMedCrossRefGoogle Scholar
  145. 145.
    Hoffman JA. Adenoviral disease in pediatric solid organ transplant recipients. Pediatr Transplant. 2006;10(1):17–25.PubMedCrossRefGoogle Scholar
  146. 146.
    Michaels MG, et al. Adenovirus infection in pediatric liver transplant recipients. J Infect Dis. 1992;165(1):170–4.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Koneru B, et al. Adenoviral infections in pediatric liver transplant recipients. JAMA. 1987;258(4):489–92.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Engelmann G, et al. Adenovirus infection and treatment with cidofovir in children after liver transplantation. Pediatr Transplant. 2009;13(4):421–8.PubMedCrossRefGoogle Scholar
  149. 149.
    Brumage LK, Wright TL. Treatment for recurrent viral hepatitis after liver transplantation. J Hepatol. 1997;26(2):440–5.PubMedCrossRefGoogle Scholar
  150. 150.
    Todo S, et al. Orthotopic liver transplantation for patients with hepatitis B virus-related liver disease. Hepatology. 1991;13(4):619–26.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Joya-Vazquez PP, et al. Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis. Transplantation. 2002;73(10):1598–602.PubMedCrossRefGoogle Scholar
  152. 152.
    Dodson SF, et al. Infectivity of hepatic allografts with antibodies to hepatitis B virus. Transplantation. 1997;64(11):1582–4.PubMedCrossRefGoogle Scholar
  153. 153.
    Ghaziani T, et al. Hepatitis B and liver transplantation: molecular and clinical features that influence recurrence and outcome. World J Gastroenterol. 2014;20(39):14142–55.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Terrault NA, et al. Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin. Hepatology. 1996;24(6):1327–33.PubMedCrossRefGoogle Scholar
  155. 155.
    Angus PW. Review: hepatitis B and liver transplantation. J Gastroenterol Hepatol. 1997;12(3):217–23.PubMedCrossRefGoogle Scholar
  156. 156.
    Mutimer D, et al. Lamivudine without HBIg for prevention of graft reinfection by hepatitis B: long-term follow-up. Transplantation. 2000;70(5):809–15.PubMedCrossRefGoogle Scholar
  157. 157.
    Perrillo RP, et al. A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B. Hepatology. 2001;33(2):424–32.PubMedCrossRefGoogle Scholar
  158. 158.
    Marzano A, et al. Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis. J Hepatol. 2001;34(6):903–10.PubMedCrossRefGoogle Scholar
  159. 159.
    Angus PW, Patterson SJ. Liver transplantation for hepatitis B: what is the best hepatitis B immune globulin/antiviral regimen? Liver Transpl. 2008;14 Suppl 2:S15–22.PubMedCrossRefGoogle Scholar
  160. 160.
    Lake JR. Do we really need long-term hepatitis B hyperimmune globulin? What are the alternatives? Liver Transpl. 2008;14 Suppl 2:S23–6.PubMedCrossRefGoogle Scholar
  161. 161.
    Roche B, et al. Rational basis for optimizing short and long-term hepatitis B virus prophylaxis post liver transplantation: role of hepatitis B immune globulin. Transplantation. 2015;99(7):1321–34.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Hussain M, et al. Presence of intrahepatic (total and ccc) HBV DNA is not predictive of HBV recurrence after liver transplantation. Liver Transpl. 2007;13(8):1137–44.PubMedCrossRefGoogle Scholar
  163. 163.
    Wright TL, et al. Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology. 1992;103(1):317–22.PubMedCrossRefGoogle Scholar
  164. 164.
    Bizollon T, et al. Hepatitis C virus recurrence after liver transplantation. Gut. 1999;44(4):575–8.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Samuel D, Feray C. Recurrent hepatitis C after liver transplantation: clinical and therapeutical issues. J Viral Hepat. 2000;7(2):87–92.PubMedCrossRefGoogle Scholar
  166. 166.
    Gane EJ, et al. A longitudinal analysis of hepatitis C virus replication following liver transplantation. Gastroenterology. 1996;110(1):167–77.PubMedCrossRefGoogle Scholar
  167. 167.
    Rosen HR, et al. Cytomegalovirus viremia: risk factor for allograft cirrhosis after liver transplantation for hepatitis C. Transplantation. 1997;64(5):721–6.PubMedCrossRefGoogle Scholar
  168. 168.
    McHutchison JG, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339(21):1485–92.PubMedCrossRefGoogle Scholar
  169. 169.
    Poynard T, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998;352(9138):1426–32.PubMedCrossRefGoogle Scholar
  170. 170.
    Everson GT, et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology. 2005;42(2):255–62.PubMedCrossRefGoogle Scholar
  171. 171.
    Forns X, et al. Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. J Hepatol. 2003;39(3):389–96.PubMedCrossRefGoogle Scholar
  172. 172.
    Pipili C, Cholongitas E. Treatment of chronic hepatitis C in liver transplant candidates and recipients: where do we stand? World J Hepatol. 2015;7(12):1606–16.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Panel AIHG. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54.CrossRefGoogle Scholar
  174. 174.
    European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):392–420.CrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Open Access This chapter is distributed under the terms of the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Department of Infectious DiseasesMayo ClinicPhoenixUSA
  2. 2.Department of Medicine/Infectious DiseasesMayo Clinic in ArizonaPhoenixUSA
  3. 3.Department of SurgeryYale New Haven HospitalNew HavenUSA

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