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Circulating markers of gut barrier function associated with disease severity in primary sclerosing cholangitis.

Liver Int; 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30269440
BACKGROUND & AIMS: One important hypothesis in primary sclerosing cholangitis (PSC) pathophysiology suggests that bacterial products from an inflamed leaky gut leads to biliary inflammation. We aimed to investigate whether circulating markers of bacterial translocation were associated with survival in a Norwegian PSC cohort.

METHODS:

Serum levels of zonulin, intestinal fatty acid binding protein, soluble CD14 (sCD14), lipopolysaccharide (LPS) and LPS-binding protein (LBP) were measured in 166 PSC patients and 100 healthy controls (HC).

RESULTS:

LBP and sCD14 were elevated in PSC compared with HC (median 13662 vs 12339 ng/mL, P=0.010 and 1657 vs. 1196 ng/mL, P<0.001, respectively). High sCD14 and LBP (values>optimal cut-off using receiver operating characteristics) were associated with reduced liver transplantation-free survival (P<0.001 and P=0.005, respectively). The concentration of sCD14 was higher in patients with hepatobiliary cancer compared to other PSC patients and HC. Zonulin was lower in PSC than controls, but when excluding PSC patients with increased prothrombin time zonulin concentrations were similar in PSC and HC. Concomitant inflammatory bowel disease did not influence the results, while IBD patients without PSC (n=40) had lower concentration of sCD14. In multivariable Cox regression, high sCD14 and high LBP were associated with transplantation-free survival, independent from Mayo risk score (HR 2.26 (95%CI 1.15-4.43), P=0.018 and HR 2.00 (95% CI 1.17-3.43), P=0.011, respectively).

CONCLUSIONS:

PSC patients show increased levels of circulating markers of bacterial translocation. High levels are associated with poor prognosis measured by transplantation-free survival, indicating that ongoing gut leakage could have clinical impact in PSC. This article is protected by copyright. All rights reserved.