Fungal translocation measured by serum 1,3‐ß‐D‐glucan correlates with severity and outcome of liver cirrhosis—A pilot study

Author:

Egger Matthias12ORCID,Horvath Angela34ORCID,Prüller Florian5ORCID,Fickert Peter3ORCID,Finkelman Malcolm6ORCID,Kriegl Lisa1,Grønbæk Henning78ORCID,Møller Holger Jon9ORCID,Prattes Juergen13ORCID,Krause Robert12ORCID,Hoenigl Martin121011ORCID,Stadlbauer Vanessa234ORCID

Affiliation:

1. Division of Infectious Diseases, Department of Internal Medicine Medical University of Graz Graz Austria

2. Biotechmed‐Graz Graz Austria

3. Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria

4. CBmed Center of Biomarker Research Graz Austria

5. Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz Graz Austria

6. Clinical Development, Associates of Cape Cod, Inc Falmouth Massachusetts USA

7. Department of Hepatology Aarhus University Hospital Aarhus Denmark

8. Department of Gastroenterology Aarhus University Hospital Aarhus Denmark

9. Department of Clinical Biochemistry Aarhus University Hospital Aarhus Denmark

10. Clinical and Translational Fungal‐Working Group University of California San Diego San Diego California USA

11. Division of Infectious Diseases and Global Public Health University of California San Diego San Diego California USA

Abstract

AbstractBackground & AimsOn a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host–pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.MethodsIncluding 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3‐β‐D‐glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.ResultsPatients with cirrhosis Child–Pugh class (CPC)‐B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2–25.2) compared to patients with cirrhosis CPC‐A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon‐gamma‐induced protein). Mortality differed significantly between patients with positive versus negative BDG (log‐rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8–26.3).DiscussionWe observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in‐depth knowledge about (fungal‐)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host–pathogen interactions and potentially introduce points of application for therapeutic interventions.

Funder

Austrian Science Fund

Publisher

Wiley

Subject

Hepatology

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