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Abstract：
BACKGROUND: Tight junction proteins (TJPs) play an important role in gut-barrier dysfunction in cirrhosis and its complications such as acute variceal bleed (AVB). However, the dynamics of TJPs expression after AVB, its relation to bacterial translocation, and impact on clinical outcome is largely unknown.
OBJECTIVE: The aim of this study was to study the expression of TJPs in cirrhosis and assess its dynamic changes in AVB. In addition, the relation of TJP expression to endotoxemia and clinical outcomes was assessed.
METHODS: In this prospective pilot study, 17 patients of cirrhosis with AVB, 59 patients of cirrhosis without AVB (non-AVB cirrhosis), and 20 controls were assessed for claudin-2 and claudin-4 expression in the duodenal biopsy. In the AVB-cirrhosis group, additional biopsies were obtained after 3 weeks. Endotoxemia was assessed by measuring IgG anti-endotoxin antibody levels. Claudin expression was correlated with a 6-month survival.
RESULTS: Claudin-2 expression was downregulated in patients with AVB and non-AVB cirrhosis in villi (P < 0.001 and 0.013) and crypts (P < 0.001 and 0.012), respectively, compared with the controls. Claudin-4 expression was similar in villi (P = 0.079), but lower in crypts (P = 0.007) in patients with cirrhosis. Claudin-2 expression was upregulated on serial biopsies in both villi and crypts (P = 0.003 and 0.001, respectively) in AVB-cirrhosis with postbleed expression comparable with those with non-AVB cirrhosis. IgG anti-endotoxin antibody levels were elevated in cirrhosis with no correlation with claudin-2/4 expression. Claudin-2 expression independently predicted survival at 6 months.
CONCLUSIONS: Both claudin-2 and claudin-4 expression are downregulated in cirrhosis. AVB is associated with dynamic changes in TJPs expression. Gut-barrier dysfunction might predict outcomes independent of bacterial endotoxemia in cirrhosis.
OBJECTIVE: The aim of this study was to study the expression of TJPs in cirrhosis and assess its dynamic changes in AVB. In addition, the relation of TJP expression to endotoxemia and clinical outcomes was assessed.
METHODS: In this prospective pilot study, 17 patients of cirrhosis with AVB, 59 patients of cirrhosis without AVB (non-AVB cirrhosis), and 20 controls were assessed for claudin-2 and claudin-4 expression in the duodenal biopsy. In the AVB-cirrhosis group, additional biopsies were obtained after 3 weeks. Endotoxemia was assessed by measuring IgG anti-endotoxin antibody levels. Claudin expression was correlated with a 6-month survival.
RESULTS: Claudin-2 expression was downregulated in patients with AVB and non-AVB cirrhosis in villi (P < 0.001 and 0.013) and crypts (P < 0.001 and 0.012), respectively, compared with the controls. Claudin-4 expression was similar in villi (P = 0.079), but lower in crypts (P = 0.007) in patients with cirrhosis. Claudin-2 expression was upregulated on serial biopsies in both villi and crypts (P = 0.003 and 0.001, respectively) in AVB-cirrhosis with postbleed expression comparable with those with non-AVB cirrhosis. IgG anti-endotoxin antibody levels were elevated in cirrhosis with no correlation with claudin-2/4 expression. Claudin-2 expression independently predicted survival at 6 months.
CONCLUSIONS: Both claudin-2 and claudin-4 expression are downregulated in cirrhosis. AVB is associated with dynamic changes in TJPs expression. Gut-barrier dysfunction might predict outcomes independent of bacterial endotoxemia in cirrhosis.
摘要：
背景：紧密连接蛋白（TJPs）在肝硬化及其并发症如急性静脉曲张出血（AVB）的肠屏障功能障碍中起重要作用。然而,AVB后TJPs表达的动力学，它与细菌易位的关系，对临床结局的影响在很大程度上是未知的。
目的：本研究的目的是研究TJPs在肝硬化中的表达并评估其在AVB中的动态变化。此外,评估了TJP表达与内毒素血症和临床结局的关系.
方法：在这项前瞻性试点研究中，17例肝硬化合并AVB，59例肝硬化无AVB（非AVB肝硬化），和20个对照组在十二指肠活检中评估了claudin-2和claudin-4的表达。在AVB肝硬化组中，3周后获得额外的活检.通过测量IgG抗内毒素抗体水平来评估内毒素血症。Claudin的表达与6个月的生存期相关。
结果：在AVB和非AVB肝硬化患者的绒毛（P<0.001和0.013）和隐窝（P<0.001和0.012）中，Claudin-2表达下调，分别,与对照组相比。claudin-4在绒毛中的表达相似(P=0.079),但低隐窝（P=0.007）的肝硬化患者。在AVB肝硬化中，绒毛和隐窝的连续活检中Claudin-2表达上调（分别为P=0.003和0.001），出血后表达与非AVB肝硬化相当。肝硬化患者IgG抗内毒素抗体水平升高，与claudin-2/4表达无相关性。Claudin-2表达独立预测6个月时的存活。
结论：claudin-2和claudin-4在肝硬化中表达均下调。AVB与TJPs表达的动态变化相关。肠屏障功能障碍可能预测结果独立于肝硬化的细菌内毒素血症。
目的：本研究的目的是研究TJPs在肝硬化中的表达并评估其在AVB中的动态变化。此外,评估了TJP表达与内毒素血症和临床结局的关系.
方法：在这项前瞻性试点研究中，17例肝硬化合并AVB，59例肝硬化无AVB（非AVB肝硬化），和20个对照组在十二指肠活检中评估了claudin-2和claudin-4的表达。在AVB肝硬化组中，3周后获得额外的活检.通过测量IgG抗内毒素抗体水平来评估内毒素血症。Claudin的表达与6个月的生存期相关。
结果：在AVB和非AVB肝硬化患者的绒毛（P<0.001和0.013）和隐窝（P<0.001和0.012）中，Claudin-2表达下调，分别,与对照组相比。claudin-4在绒毛中的表达相似(P=0.079),但低隐窝（P=0.007）的肝硬化患者。在AVB肝硬化中，绒毛和隐窝的连续活检中Claudin-2表达上调（分别为P=0.003和0.001），出血后表达与非AVB肝硬化相当。肝硬化患者IgG抗内毒素抗体水平升高，与claudin-2/4表达无相关性。Claudin-2表达独立预测6个月时的存活。
结论：claudin-2和claudin-4在肝硬化中表达均下调。AVB与TJPs表达的动态变化相关。肠屏障功能障碍可能预测结果独立于肝硬化的细菌内毒素血症。
