Background: Invasive fungal infection (IFI) is associated with high mortality after living donor liver transplant (LDLT). The aim of this study was to identify the risk factors for post-LDLT IFI for early diagnosis and improvement of antifungal treatment outcome. Methods: Risk analysis data were available for all 153 patients who underwent LDLT between January 2005 and April 2012. Results: During the follow-up period (1,553 ± 73 days, range 20–2,946 days), 15 patients (9.8%) developed IFI classified as “proven” (n = 8) and “probable” (= 7) with fungal pathogens including Candida spp. (n = 10), Aspergillus spp. (n = 4), and Trichosporon (n = 2). Of these patients, 7 patients with IFI died despite treatment. The 1-, 3-, and 5-year survival rates were lower in patients with IFI than those without IFI (66.7/59.3/44.4 vs. 90.4/85.7/81.8%, respectively; p = 0.0026). Multivariate analysis identified model for end-stage liver disease score of ≥26 (OR 16.0, p = 0.0012) and post-transplant acute kidney injury (RIFLE criteria I- or F-class; OR 4.87, p = 0.047) as independent risk factors for IFI. Conclusion: Preoperative recipients’ status and postoperative kidney dysfunction can affect an occurrence of post-transplant IFI. These risk factors would be taken into consideration for designation of proper antifungal therapy.

1.
Beck-Sague C, Jarvis WR: Secular trends in the epidemiology of nosocomial fungal -infections in the United States, 1980–1990. National nosocomial infections surveillance system. J Infect Dis 1993; 167: 1247–1251.
2.
Jarvis WR: Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 1995; 20: 1526–1530.
3.
Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, Freifeld A, et al: Invasive fungal infections among organ transplant recipients: results of the transplant-associated infection surveillance network (TRANSNET). Clin Infect Dis 2010; 50: 1101–1111.
4.
Linares L, Garcia-Goez JF, Cervera C, Almela M, Sanclemente G, Cofan F, et al: Early bacteremia after solid organ transplantation. Transplant Proc 2009; 41: 2262–2264.
5.
Hagerty JA, Ortiz J, Reich D, Manzarbeitia C: Fungal infections in solid organ transplant patients. Surg Infect (Larchmt) 2003; 4: 263–271.
6.
Eschenauer GA, Lam SW, Carver PL: Antifungal prophylaxis in liver transplant recipients. Liver Transpl 2009; 15: 842–858.
7.
Arnow PM: Infections following orthotopic liver transplantation. HPB Surg 1991; 3: 221–232; discussion 232–223.
8.
Aikawa N, Sumiyama Y, Kusachi S, Hirasawa H, Oda S, Yamazaki Y: Use of antifungal agents in febrile patients nonresponsive to antibacterial treatment: the current status in surgical and critical care patients in Japan. J Infect Chemother 2002; 8: 237–241.
9.
Suzuki T, Hashimoto T, Nakamura T, Kondo S, Shimizu Y, Nakamura Y, et al: Fungal infection in living related liver transplantation patients. Transplant Proc 2000; 32: 2231–2232.
10.
Silveira FP, Husain S: Fungal infections in solid organ transplantation. Med Mycol 2007; 45: 305–320.
11.
Singh N, Wagener MM, Marino IR, Gayowski T: Trends in invasive fungal infections in liver transplant recipients: correlation with evolution in transplantation practices. Transplantation 2002; 73: 63–67.
12.
Husain S, Tollemar J, Dominguez EA, Baumgarten K, Humar A, Paterson DL, et al: Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study. Transplantation 2003; 75: 2023–2029.
13.
Fortun J, Martin-Davila P, Moreno S, De Vicente E, Nuno J, Candelas A, et al: Risk factors for invasive aspergillosis in liver transplant recipients. Liver Transpl 2002; 8: 1065–1070.
14.
Collins LA, Samore MH, Roberts MS, Luzzati R, Jenkins RL, Lewis WD, et al: Risk factors for invasive fungal infections complicating orthotopic liver transplantation. J Infect Dis 1994; 170: 644–652.
15.
Fung JJ. Fungal infection in liver transplantation. Transpl Infect Dis 2002; 4(suppl 3):18–23.
16.
Kawagishi N, Satoh K, Enomoto Y, Akamatsu Y, Sekiguchi S, Fujimori K, et al: Risk factors and impact of beta-D glucan on invasive fungal infection for the living donor liver transplant recipients. Tohoku J Exp Med 2006; 209: 207–215.
17.
Osawa M, Ito Y, Hirai T, Isozumi R, Takakura S, Fujimoto Y, et al: Risk factors for invasive aspergillosis in living donor liver transplant recipients. Liver Transpl 2007; 13: 566–570.
18.
Ohkubo T, Sugawara Y, Takayama T, Kokudo N, Makuuchi M: The risk factors of fungal infection in living-donor liver transplantations. J Hepatobiliary Pancreat Sci 2012; 19: 382–388.
19.
Li C, Wen TF, Mi K, Wang C, Yan LN, Li B: Analysis of infections in the first 3-month after living donor liver transplantation. World J Gastroenterol 2012; 18: 1975–1980.
20.
Kamath PS, Kim WR: The model for end-stage liver disease (MELD). Hepatology 2007; 45: 797–805.
21.
Bellomo R, Kellum JA, Ronco C: Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria. Intensive Care Med 2007; 33: 409–413.
22.
Utsumi M, Umeda Y, Sadamori H, Nagasaka T, Takaki A, Matsuda H, et al: Risk factors for acute renal injury in living donor liver transplantation: evaluation of the RIFLE criteria. Transpl Int 2013; 26: 842–852.
23.
Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al: Clinical practice guidelines for the management of candidiasis: 2009 update by the infectious diseases society of America. Clin Infect Dis 2009; 48: 503–535.
24.
Fungal infections. Am J Transplant 2004; 4(suppl 10):110–134.
25.
Playford EG, Webster AC, Sorrell TC, Craig JC: Systematic review and meta-analysis of antifungal agents for preventing fungal infections in liver transplant recipients. Eur J Clin Microbiol Infect Dis 2006; 25: 549–561.
26.
Sun HY, Cacciarelli TV, Singh N: Micafungin versus amphotericin B lipid complex for the prevention of invasive fungal infections in high-risk liver transplant recipients. Transplantation 2013; 96: 573–578.
27.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al: Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the National institute of allergy and infectious diseases mycoses study group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821.
28.
Bradburn MJ, Clark TG, Love SB, Altman DG: Survival analysis Part III: multivariate data analysis – choosing a model and assessing its adequacy and fit. Br J Cancer 2003; 89: 605–611.
29.
Bellier C, Bert F, Durand F, Retout S, Belghiti J, Mentre F, et al: Risk factors for Enterobacteriaceae bacteremia after liver transplantation. Transpl Int 2008; 21: 755–763.
30.
Selzner M, Kashfi A, Cattral MS, Selzner N, McGilvray ID, Greig PD, et al: Live donor liver transplantation in high MELD score recipients. Ann Surg 2010; 251: 153–157.
31.
Saliba F, Delvart V, Ichai P, Kassis N, Botterel F, Mihaila L, et al: Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era. Clin Transplant 2013; 27:E454–E461.
32.
Lichtenstern C, Hochreiter M, Zehnter VD, Brenner T, Hofer S, Mieth M, et al: Pretransplant model for end stage liver disease score predicts posttransplant incidence of fungal infections after liver transplantation. Mycoses 2013; 56: 350–357.
33.
Karchmer AW, Samore MH, Hadley S, Collins LA, Jenkins RL, Lewis WD: Fungal infections complicating orthotopic liver transplantation. Trans Am Clin Climatol Assoc 1995; 106: 38–47; discussion 47–48.
34.
Fortun J, Martin-Davila P, Montejo M, -Munoz P, Cisneros JM, Ramos A, et al: Prophylaxis with caspofungin for invasive fungal infections in high-risk liver transplant recipients. Transplantation 2009; 87: 424–435.
35.
Kishino S, Ohno K, Shimamura T, Furukawatodo H: Optimal prophylactic dosage and disposition of micafungin in living donor liver recipients. Clin Transplant 2004; 18: 676–680.
36.
Saliba F, Dupont B: Renal impairment and amphotericin B formulations in patients with invasive fungal infections. Med Mycol 2008; 46: 97–112.
37.
Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A: A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC collaborative study group. Clin Infect Dis 2000; 31: 1155–1163.
38.
Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, et al: Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007; 369: 1519–1527.
39.
Persat F, Ranque S, Derouin F, Michel-Nguyen A, Picot S, Sulahian A: Contribution of the (1–>3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 2008; 46: 1009–1013.
40.
Presterl E, Parschalk B, Bauer E, Lassnigg A, Hajdu S, Graninger W: Invasive fungal infections and (1,3)-beta-D-glucan serum concentrations in long-term intensive care patients. Int J Infect Dis 2009; 13: 707–712.
41.
Yamanouchi K, Takatsuki M, Hidaka M, Soyama A, Kanematsu T, Eguchi S: Significance of serum β-D-glucan levels in recipients of living donor liver transplantation. J Hepatobiliary Pancreat Sci 2011; 18: 432–435.
42.
Usami M, Ohata A, Horiuchi T, Nagasawa K, Wakabayashi T, Tanaka S: Positive (1–>3)-beta-D-glucan in blood components and release of (1–>3)-beta-D-glucan from depth-type membrane filters for blood processing. Transfusion 2002; 42: 1189–1195.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.