New approaches for the detection of invasive fungal diseases in patients following liver transplantation—results of an observational clinical pilot study

Langenbeck's Archives of Surgery volume 404, pages309–325(2019)Cite this article

Abstract

Purpose

Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses.

Methods

Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX.

Results

A NGS-based diagnostic approach was shown to be suitable for the early identification of fungal pathogens in patients following LTX. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with an IFD.

Conclusion

Plasma measurements of MR-proADM and IL-17A as well as a NGS-based diagnostic approach were shown to be attractive methodologies to attenuate the weaknesses of routinely used culture-based diagnostic procedures for the determination of an IFD in patients following LTX. However, an additional confirmation within a larger multicenter trial needs to be recommended.

Trial registration

German Clinical Trials Register: DRKS00005480.

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Acknowledgements

We would like to thank Ute Krauser and Karolina Glanz for their excellent technical assistance.

Funding

The study was conducted with the financial support of the Department of Anesthesiology (Heidelberg University Hospital, Germany) and Fraunhofer IGB (Stuttgart, Germany). Furthermore, this study received financial grants from the B. Braun Foundation, Melsungen, as well as the Heidelberg Foundation of Surgery, and was supported by the European Union grant Fungitect. MR-proADM measurements were carried out by BRAHMS GmbH.

Author information

Author notes

  1. Thorsten Brenner and Kai Sohn share senior authorship.

Affiliations

  1. Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Sebastian O. Decker, Albert Krüger, Henryk Wilk, Felix C. F. Schmitt, Florian Uhle, Markus A. Weigand & Thorsten Brenner

  2. Fraunhofer IGB, Nobelstraße 12, 70569, Stuttgart, Germany

    Silke Grumaz, Yevhen Vainshtein & Kai Sohn

  3. Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120, Heidelberg, Germany

    Thomas Bruckner

  4. Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany

    Stefan Zimmermann

  5. Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Arianeb Mehrabi & Markus Mieth

  6. Department of Internal Medicine IV, Heidelberg University Hospital, Im Neunheimer Feld 410, 69120, Heidelberg, Germany

    Karl Heinz Weiss

  7. Department of Anesthesiology, Westpfalzklinikum, Hellmut-Hartert-Straße 1, 67655, Kaiserslautern, Germany

    Stefan Hofer

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Contributions

SOD conceived the study, participated in its design and coordination, and helped in drafting the article. Furthermore, he performed data acquisition, carried out the measurements in the laboratory, and prepared the tables and figures. AK and HW performed data acquisition and were involved in critical revision of the article. FU, FCFS, AM, MM, KHW, MAW, and SH participated in the design of the study and were involved in revising the article. TBru participated in the design of the study and performed the statistical analysis. SZ performed all microbiological analyses and was involved in critical revision of the article. SG, YV, and KS were responsible for NGS-based diagnostics and revised the article critically. TBre conceived the study, participated in its design and coordination, and drafted the article. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kai Sohn or Thorsten Brenner.

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The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Decker, S.O., Krüger, A., Wilk, H. et al. New approaches for the detection of invasive fungal diseases in patients following liver transplantation—results of an observational clinical pilot study. Langenbecks Arch Surg 404, 309–325 (2019). https://doi.org/10.1007/s00423-019-01769-y

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Keywords

  • Candida spp.
  • Aspergillus spp.
  • Next-generation sequencing
  • Interleukin-17A
  • ß-D-glucan
  • Mid-regional proadrenomedullin