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Clin Res Hepatol Gastroenterol. 2019 Apr 30. pii: S2210-7401(18)30272-9. doi: 10.1016/j.clinre.2018.11.014. [Epub ahead of print]

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

Author information

1
Department of Gastroenterology and Hepatology, Jiangxi Provincial people's hospital, Nanchang University, No. 152 Aiguo Road, Nanchang, 330006 Jiangxi Province, China.
2
Gastroenterology and Operative Endoscopy Unit, Siena University Hospital, Siena, Italy.
3
Department of Gastroenterology and Hepatology, Jiangxi Provincial people's hospital, Nanchang University, No. 152 Aiguo Road, Nanchang, 330006 Jiangxi Province, China. Electronic address: Hjf5513@126.com.

Abstract

OBJECTIVE:

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

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Claudin-3; D-lactate; Interferon gamma; Intestinal endotoxemia; Liver cirrhosis; Tumor necrosis factor-alpha

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