Wang ZhaoHan, Wang Aiyao, Gong Zhibin, Biviano Ivano, Liu Hui, Hu Jianfang
Department of Gastroenterology and Hepatology, Jiangxi Provincial people's hospital, Nanchang University, No. 152 Aiguo Road, Nanchang, 330006 Jiangxi Province, China.
Gastroenterology and Operative Endoscopy Unit, Siena University Hospital, Siena, Italy.
Clin Res Hepatol Gastroenterol. 2019 Aug;43(4):410-416. doi: 10.1016/j.clinre.2018.11.014. Epub 2019 Apr 30.
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.
研究肝硬化（LC）患者的肠源性内毒素血症（IETM）、肠道通透性（IP）及细胞因子活性。
招募29例慢性乙型肝炎（CHB）患者、28例代偿期LC患者、33例失代偿期LC患者、24例自发性细菌性腹膜炎（SBP）患者、26例慢加急性肝衰竭（ACLF）患者以及24例合并肝细胞癌（HCC）的失代偿期LC患者。纳入31名健康人作为对照组。检测血浆肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、D-乳酸、内毒素及紧密连接蛋白3水平。采用Pearson相关性检验和方差分析比较数据，P < 0.05为差异有统计学意义。
与对照组相比，所有肝病患者血浆中的TNF-α、紧密连接蛋白3及内毒素水平均显著升高（P < 0.05），尤其是失代偿期LC、SBP、ACLF或HCC患者（P < 0.01）。HCC患者的IFN-γ显著高于其他肝病患者（P < 0.01）。除SBP外，所有肝病患者的血浆D-乳酸均显著降低（P < 0.01）。TNF-α、内毒素及紧密连接蛋白3水平呈正相关（P < 0.01），但IFN-γ与内毒素或紧密连接蛋白3的相关性不显著。血浆D-乳酸水平与TNF-α、内毒素或紧密连接蛋白3水平均无显著相关性。
发现血浆紧密连接蛋白3而非D-乳酸是肝病患者IP的标志物。此类患者血浆TNF-α升高可能损伤肠道屏障，导致IETM，尤其是在终末期LC患者中。
