Skip to main content

Advertisement

Log in

Invasive pulmonary aspergillosis after liver transplantation: lessons from successfully treated cases and review of the literature

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center.

Methods

We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully.

Results

Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized.

Conclusions

Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Paterson DL, Singh N. Invasive aspergillosis in transplant recipients. Medicine. 1999;78(2):123–38.

    Article  CAS  Google Scholar 

  2. Barchiesi F, Mazzocato S, Mazzanti S, Gesuita R, Skrami E, Fiorentini A, et al. Invasive aspergillosis in liver transplant recipients: epidemiology, clinical characteristics, treatment, and outcomes in 116 cases. Liver Transpl. 2015;21(2):204–12.

    Article  Google Scholar 

  3. Hellinger WC, Bonatti H, Yao JD, Alvarez S, Brumble LM, Keating MR, 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.

    Article  Google Scholar 

  4. Husain S, Camargo JF. Invasive Aspergillosis in solid-organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transpl. 2019;33:1–24.

    Article  Google Scholar 

  5. Saliba F, Delvart V, Ichai P, et al. Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era. Clin Transplant. 2013;27(4):e454–61.

    Article  Google Scholar 

  6. Nagao M, Fujimoto Y, Yamamoto M, Matsumura Y, Kaido T, Takakura S, et al. Epidemiology of invasive fungal infections after liver transplantation and the risk factors of late-onset invasive aspergillosis. J Infect Chemother. 2016;22(2):84–9.

    Article  Google Scholar 

  7. 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;13:566–70.

    Article  Google Scholar 

  8. 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;19:382–8.

    Article  Google Scholar 

  9. Pham CD, Reiss E, Hagen F, Meis JF, Lockhart SR. Passive surveillance for azole-resistant Aspergillus fumigatus, United States, 2011–2013. Emerg Infect Dis. 2014;20(9):1498–503.

    Article  CAS  Google Scholar 

  10. Kohno S. The guidelines for management of deep-seated mycoses. Tokyo: Kyowa Kikaku; 2014. p. 173–81.

    Google Scholar 

  11. Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of Aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63:e26–7.

    Article  Google Scholar 

  12. Robinson L, Reed E, Galbraith T, Alonso A, Moulton AL, Fleming WH, et al. Pulmonary resection for invasive Aspergillus infections in immunocompromised patients. J Thorac Cardiovasc Surg. 1995;109(6):1182–97.

    Article  CAS  Google Scholar 

  13. Takeda K, Morioka D, Matsuo K, Endo I, Sekido H, Moroboshi T, et al. A case of successful resection after long-term medical treatment of invasive pulmonary aspergillosis following living donor liver transplantation. Transplant Proc. 2007;39(10):3505–8.

    Article  CAS  Google Scholar 

  14. Mochida S, Takikawa Y, Nakayama N, Oketani M, Naiki T, Yamagishi Y, et al. Diagnostic criteria of acute liver failure: a report by the Intractable Hepato-Biliary Diseases. Study group of Japan. Hepatol Res. 2011;41:805–12.

    Article  Google Scholar 

  15. Sugawara K, Nakayama N, Mochida S. Acute liver failure in Japan: definition, classification, and prediction of the outcome. J Gastroenterol. 2012;47:849–61.

    Article  Google Scholar 

  16. Pauw BD, 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;46:1813–21.

    Article  Google Scholar 

  17. Shinoda M, Tanabe M, Kawachi S, Ono Y, Hayakawa T, Iketani O, et al. Pharmacokinetics of mizoribine in adult living donor liver transplantation. Transplant Proc. 2012;44:1329–35.

    Article  CAS  Google Scholar 

  18. Tanabe M, Kawachi S, Obara H, Shinoda M, Hibi T, Kitagawa Y, et al. Current progress in ABO-incompatible liver transplantation. Eur J Clin Investig. 2010;40:943–9.

    Article  Google Scholar 

  19. Rivosecchi RM, Clancy CJ, Shields RK, Ensor CR, Shullo MA, Falcione BA, et al. Effects of isavuconazole on the plasma concentrations of tacrolimus among solid-organ transplant patients. Antimicrob Agents Chemother. 2017;61(9):e00970-e1017. https://doi.org/10.1128/AAC.00970-17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Groll AH, Desai A, Han D, Howieson C, Kato K, Akhtar S, et al. Pharmacokinetic Assessment of drug-drug interactions of isavuconazole with the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Clin Pharmacol Ther. 2017;6(1):76–85.

    CAS  Google Scholar 

  21. Furtun J, Martin-Davila P, Moreno S, Vicente ED, Nuño J, Candelas A, et al. Risk factors for invasive aspergillosis in liver transplant recipients. Liver Transpl. 2002;8:1065–70.

    Article  Google Scholar 

  22. Umeshita K, Eguchi S, Egawa H, Haga H, Kasahara M, Kokudo N, et al. Liver transplantation in Japan: Registry by the Japanese Liver Transplantation Society. Hepatol Res. 2019;49(9):964–80.

    Article  Google Scholar 

  23. Herbrecht R, Denning D, Patterson T, Bennett JE, Greene RE, Oestmann JW, et al. Voricanozole versus amphotericin B for primary therapy of invasive Aspergillosis. N Engl J Med. 2002;347(6):408–15.

    Article  CAS  Google Scholar 

  24. Resendiz-Sharpe A, Mercier T, Lestrade PPA, van der Beek MT, von dem Borne PA, Cornelissen JJ, et al. Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients. J Antimicrob Chemother. 2019;74(9):2759–66.

    Article  CAS  Google Scholar 

  25. Rudramurthy SM, Paul RA, Chakrabarti A, Mouton JW, Meis JF. Invasive Aspergillosis by Aspergillus flavus: epidemiology, diagnosis, antifungal resistance, and management. J Fungi. 2019;5(55):1–23.

    Google Scholar 

  26. Hashimoto A, Hagiwara D, Watanabe A, Yahiro M, Yikelamu A, Yaguchi T, et al. Drug Sensitivity and resistance mechanism in Aspergillus section Nigri strains from Japan. Antimicrob Agents Chemother. 2017;61(8):1–10.

    Article  Google Scholar 

  27. Tetsuka N, Yaguchi T, Machida H, Ito S, Miyairi I. Invasive pulmonary aspergillosis due to azole-resistant Aspergillus lentulus. Pediatr Int. 2017;59(3):362–3.

    Article  Google Scholar 

  28. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24:1–38.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Dr. Katsuhiko Kamei, Professor of Medical Mycology Research Center, Chiba University in Japan, for his help with the identification of some fungal isolates.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masahiro Shinoda.

Ethics declarations

Conflict of interest

There are some conflicts of interest to declare: Masahiro Shinoda, Eisai Co., Ltd and Taiho pharmaceutical Co., Ltd; Yuko Kitagawa, ONO PHARMACEUTICAL CO., LTD., Bristol-Myers Squibb, Olympus Corporation, AsahiKASEI Co., Ltd., TAIHO PHARMACEUTICAL CO., LTD., CHUGAI PHARMACEUTICAL CO., LTD., Otsuka Pharmaceutical Co., Ltd., TSUMURA & CO., Takeda Pharmaceutical Co., Ltd., MEDICON INC., Yakult Honsha Co., Ltd., EA Pharma Co. Ltd., Eisai Co. Ltd.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 17 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abe, K., Shinoda, M., Uno, S. et al. Invasive pulmonary aspergillosis after liver transplantation: lessons from successfully treated cases and review of the literature. Surg Today 51, 1361–1370 (2021). https://doi.org/10.1007/s00595-021-02263-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-021-02263-z

Keywords

Navigation