Plasma claudin-3 is associated with tumor necrosis factor-alpha-induced intestinal endotoxemia in liver disease

To investigate intestinal endotoxemia (IETM), intestinal permeability (IP) and cytokine activity in patients with liver cirrhosis (LC).

Twenty-nine patients with chronic hepatitis B (CHB), 28 with compensated LC, 33 with decompensated LC, 24 with spontaneous bacterial peritonitis (SBP), 26 with acute-on-chronic liver failure (ACLF), and 24 with decompensated LC complicated by hepatocellular carcinoma (HCC) were recruited. Thirty-one healthy people were included as a control group. Plasma tumor necrosis factor (TNF)-α, interferon (IFN)-γ, D-lactate, endotoxin, and claudin-3 levels were assayed. Data were compared using Pearson correlation testing and analysis of variance, with P < 0.05 considered significant.

TNF-α, claudin-3, and endotoxin levels were significantly increased (P < 0.05) in the plasma of all patients with liver disease compared with that of controls, particularly in patients with decompensated LC, SBP, ACLF, or HCC (P < 0.01). IFN-γ was significantly higher in HCC than in other liver diseases (P < 0.01). Plasma D-lactate was significantly decreased in all liver diseases, except SBP (P < 0.01). TNF-α, endotoxin, and claudin-3 levels were positively correlated (P < 0.01), but correlations of IFN-γ with endotoxin or claudin-3 were not significant. The plasma D-lactate level did not significantly correlate with either TNF-α, endotoxin, or claudin-3 levels.

Plasma claudin-3, but not D-lactate, was found to be a marker of IP in patients with liver diseases. Elevated plasma TNF-α in such patients was likely to have injured the intestinal barrier, leading to IETM, especially in end-stage LC.