NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients

Jüngst, Christoph; Stadlbauer, Vanessa; Reichert, Matthias; Zimmer, Vincent; Weber, Susanne N.; Ofner-Ziegenfuss, Lisa; Voigtländer, Torsten; Spindelböck, W; Fickert, Peter; Kirchner, Gabriele I.; Lankisch, Tim O.; Krawczyk, Marcin

doi:10.1038/s41598-017-06268-y

Cited by 9 publications

(5 citation statements)

References 31 publications

(43 reference statements)

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“…This suggests, that gut barrier dysfunction is a feature of the critical illness and that a "second hit" that yet needs to be defined is necessary to develop SC-CIP. NOD2 polymorphisms, but not polymorphisms in genes associated with cholestatic liver diseases, were more common in SC-CIP [114].…”

Section: Sscmentioning

confidence: 85%

The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl

Stadlbauer

2021

Nutrients

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The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.

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Section: Sscmentioning

confidence: 85%

The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl

Stadlbauer

2021

Nutrients

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“…The pathogenesis of SC-CIP remains widely enigmatic, and several potentially causative factors are of major interest: (i) ischemic injury of the biliary system, (ii) bile cast formation with protein-rich sludge and (iii) impaired innate immunity leading to recurrent biliary infections with bacteria and fungi [ 5 , 6 ]. The disease may cause destruction of the intra- and extra-hepatic biliary system with evolution of strictures leading to biliary-type liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

et al. 2020

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Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut–liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut–liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment.

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“…Etwa die Hälfte benötigte einen PEEP > 10 cm H 2 O [11]. Weitere mögliche Risikofaktoren sind Bauchlage und Adipositas [12], sowie eine Mutation im NOD2-Gen [13]. Pathogenetisch weniger relevant scheinen die Dauer der mechanischen Ventilation, eine Sedierung mit Propofol und/ oder Ketamin, totale parenterale Ernährung oder Antibiotikatherapie.…”

Section: Riskofaktoren Pathomechanismusunclassified

Sekundär sklerosierende Cholangitis bei kritisch Kranken

2019

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ZusammenfassungDie sklerosierende Cholangitis der kritisch Kranken (secondary cholangitis of the critically ill patient: SC-CIP) ist eine relativ neue Entität innerhalb der sekundären Cholangitiden. Sie entwickelt sich in der Folge einer intensivmedizinischen Behandlung mit Beatmung und Katecholamintherapie. Pathophysiologische Grundlage ist eine ischämische oder immunologische Schädigung der intrahepatischen Gallenwege, die sich verselbstständigt und über das Ende der Intensivtherapie hinaus fortbesteht. Klinisch und laborchemisch findet sich zunächst eine akute Cholangitis mit einem Anstieg von CRP, gamma-GT, AP und Bilirubin. Die ERCP zeigt Schäden an den kleinen Gallenwegen mit Kalibersprüngen und biliären Ausgusskonkrementen. Die darauf folgende chronische Phase verläuft oligosymptomatisch. Alle Laborparameter bleiben aber leicht erhöht; in ERCP und MRCP zeigt sich ein fortschreitender Untergang der intrahepatischen Gallenwege. Die Langzeitprognose ist schlecht. Auch unter einer Therapie mit UDCA entwickelt die Mehrzahl der Patienten innerhalb von Monaten bis wenigen Jahren eine Leberzirrhose.

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NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients

Cited by 9 publications

References 31 publications

The Gut-Liver Axis in Cholestatic Liver Diseases

The Gut-Liver Axis in Cholestatic Liver Diseases

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

Sekundär sklerosierende Cholangitis bei kritisch Kranken

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