Abstract
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.
Highlights
Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare, often rapidly advancing, cholestatic liver disease observed in patients without known liver disease after long-term treatment in an intensive care unit (ICU)
Eighteen patients with SC-CIP, 11 patients after treatment at an ICU without liver pathologies, 21 patients with alcohol-induced cirrhosis and 21 healthy controls were included in the analysis (SC-CIP: mean age 59 ± 13 years, 13 men, mean body mass index (BMI): 27.2 ± 5.3 kg/m2 ; CIP controls: mean age 54 ± 15 years, 8 men, BMI: 25.5 ± 3.0 kg/m2 ; cirrhosis: mean age 58 ± 9 years, 16 men, BMI 27.3 ± 5.0 kg/m2 ; healthy: mean age 58 ± 7 years, 9 men, mean BMI: 25.3 ± 3.1 kg/m2 )
Our study suggests that this may be a consequence of the intensive care treatment rather than an effect of the liver disease alone, since increased gut permeability could be shown in CIP controls
Summary
Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare, often rapidly advancing, cholestatic liver disease observed in patients without known liver disease after long-term treatment in an intensive care unit (ICU). Long-term ICU treatment with a mean duration of 30 to 40 days precedes the onset of this disease, but in an individual case, development of SC-CIP after only nine days of ICU stay has been reported [1,4]. 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. Some cases may rapidly progress to cirrhosis within months, with the need for liver transplantation as the ultimate treatment option [6]
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