Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Blesl, A.
The gut-liver-axis in secondary sclerosing cholangitis after critical illness
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medical University of Graz; 2021. pp. 103
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Blesl Andreas
- Betreuer*innen:
- Hoegenauer Christoph
- Moissl-Eichinger Christine
- Stadlbauer-Köllner Vanessa
- Altmetrics:
- Abstract:
- Background: The rare chronic cholestatic liver disease secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs in patients after long-term intensive care treatment with invasive ventilation and hemodynamic support without prior liver pathology. Aims: We aimed to describe the healthy gut-liver axis and to outline pathological disruptions of this equilibrium in chronic cholestatic liver diseases. We planned to assess the stool microbiome composition, gut permeability, bacterial translocation, and serum bile acid profiles of SC-CIP patients compared to patients after critical illness without liver disease (CIP controls), patients with cirrhosis, and healthy controls within a case-control study. Furthermore, we aimed to evaluate the frequency and characteristics of gastrointestinal bleedings in SC-CIP with a retrospective analysis. Methods: We conducted a narrative review outlining the actual knowledge about the gut-liver axis in chronic cholestatic liver diseases. 16S rDNA was isolated from stool of the four cohorts and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 and lipopolysaccharide-binding protein were determined in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). For the retrospective part concerning gastrointestinal bleedings, patients with diagnosed SC-CIP were identified and compared to a control group of patients with history of intensive care treatment after cardiac surgery, but without development of SC-CIP. Results: With the conducted review, we could demonstrate that the gut-liver axis is altered in chronic cholestatic liver diseases and that observed alterations seem to play a role in the pathogenesis of these diseases. Eighteen SC-CIP patients, 11 CIP controls, 21 cirrhotic patients, and 21 healthy controls were included in the microbiome analysis. The microbiome of SC-CIP patients showed reduced alpha diversity and altered beta diversity compared to healthy controls. A shift towards pathogenic taxa and an oralization of the fecal microbiome was observed. Impaired gut permeability, elevation of biomarkers of bacterial translocation, and an altered serum bile acid profile were further recognized in SC-CIP. CIP controls also showed decreased diversity and a changed taxonomic composition of the microbiome compared to healthy controls. Fifty-three patients with SC-CIP and 19 controls were included in the retrospective study. Frequency of gastrointestinal bleeding was 30% in SC-CIP (16 patients) and 5% in the control group (1 patient) (p=0.03). In SC-CIP, 13 bleedings were reported in the upper gastrointestinal tract. Most common reasons for bleeding were gastroduodenal ulcers. Conclusion: The gut–liver axis is altered in SC-CIP. The liver disease cannot solely be accused to induce these alterations, since there seems to be an additional lasting effect of the long-term intensive care treatment on microbiome composition. Gastrointestinal bleeding is a frequent complication in patients with SC-CIP, but it remains to be determined which factor is responsible for this susceptibility.