Comparative analysis of surrogate markers of intestinal permeability, bacterial translocation, and gut vascular barrier damage in cirrhosis

Background & aims: Portal hypertension, impaired gut barrier function, and pathological bacterial translocation are hallmarks of advanced liver disease, driving the complications of cirrhosis. As measuring gut barrier function is demanding, surrogate markers have been proposed; however, their intercorrelation and applicability across different stages of advanced liver disease, particularly in ACLF, is largely unknown.

Methods: proposed markers of gut barrier dysfunction and bacterial translocation were quantified in sera from 160 patients with cirrhosis across different disease stages of compensated and decompensated cirrhosis, as well as in hepatic and portal vein serum from 20 patients before and after the insertion of a transjugular intrahepatic portosystemic stent (TIPS) using ELISA.

Results: Across all stages of liver disease, the gut vascular barrier marker plasmalemma vesicle protein-1 (PV-1) correlated with the bacterial translocation markers endogenous endotoxin-core IgA antibodies (EndoCAb) and LPS-binding protein (LBP), but not with the intestinal damage markers intestinal fatty acid binding protein (I-FABP) and zonulin-family peptides (ZFP). PV-1 and EndoCAb levels were higher in decompensated cirrhosis patients without a further increase in ACLF. Among the investigated markers, only I-FABP was correlated with the portosystemic pressure gradient, and TIPS insertion significantly reduced portal concentrations within 24h hours. Higher PV-1 levels indicated poor transplant-free survival in univariate and multivariate analyses.

Conclusions: The investigated surrogate markers of bacterial gut barrier dysfunction and bacterial translocation appear to have limited use in advanced stages of cirrhosis and are confounded by hepatic synthesis capacity, portal congestion, and acute-phase responses.

Publication History

Article published online:
20 January 2025