Surrogate Markers of Intestinal Permeability, Bacterial Translocation and Gut-Vascular Barrier Damage Across Stages of Cirrhosis

Background and AimsPortal hypertension, gut barrier dysfunction, and pathological bacterial translocation are hallmarks of cirrhosis driving complications. As measuring gut barrier function is demanding, surrogate markers have been proposed, but their intercorrelation and applicability across different stages of advanced liver disease, particularly in acute-on-chronic liver failure (ACLF), are largely unknown.MethodsProposed 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 from 20 patients in hepatic and portal vein serum before and after the insertion of transjugular intrahepatic portosystemic stent (TIPS) using enzyme-linked immunosorbent assay (ELISA).ResultsAcross all stages of liver disease, the gut-vascular barrier (GVB) marker plasmalemma vesicle protein-1 (PV-1) correlated with bacterial translocation markers endogenous endotoxin-core IgA antibodies (EndoCAb) and LPS-binding protein (LBP) but not with intestinal damage markers intestinal fatty acid binding protein (I-FABP) and zonulin-family peptides (ZFP). PV-1 and EndoCAb were higher in decompensated cirrhosis without further increase in ACLF. Among investigated markers, only I-FABP correlated with the portosystemic pressure gradient, and TIPS insertion significantly reduced portal concentrations within 24 h. Higher PV-1 levels indicated poor transplant-free survival in univariate and multivariable analysis.ConclusionsSurrogate markers of bacterial gut barrier dysfunction and bacterial translocation like ZFP, LBP and EndoCAb appear of limited use in advanced stages of cirrhosis and are confounded by hepatic synthesis capacity, portal congestion and acute phase responses. The prognostic implications of circulating PV-1 in decompensated cirrhosis levels demand further investigation.