Tranah Thomas Henry, Edwards Lindsey A, Schnabl Bernd, Shawcross Debbie Lindsay
Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, FoLSM, King's College London, London, UK.
Medicine, University of California San Diego, San Diego, California, USA.
Gut. 2021 May;70(5):982-994. doi: 10.1136/gutjnl-2020-320786. Epub 2020 Oct 15.
Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mucosal immune homoeostasis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies targeted at restoring intestinal eubiosis, augmenting gut barrier function and ameliorating the mucosal and systemic immune deficits that characterise and define the course of decompensated cirrhosis.
肝硬化门静脉高压症的特征是出现腹水、肝性脑病、门静脉高压出血和肝肾综合征等失代偿事件，这些事件发生在肝硬化相关免疫功能障碍（CAID）的背景下，并决定发病率和预后。CAID描述了一种二分法观察结果，即全身免疫细胞被激活并表现出炎症表型，但对病原体挑战却无法产生强有力的反应。包括自发性细菌性腹膜炎在内的细菌感染是晚期慢性肝病的常见并发症，可促使静脉曲张出血、肝肾综合征和慢加急性肝衰竭的发生；它们通常源于肠道来源的微生物，并且与晚期慢性肝病中共生肠道微生物群的生态失调密切相关。在此我们综述晚期慢性肝病中发生的肝硬化生态失调、肠道屏障功能障碍以及宿主-微生物群分隔和黏膜免疫稳态缺陷之间的联系。我们讨论了旨在恢复肠道微生态平衡、增强肠道屏障功能以及改善失代偿期肝硬化病程特征并决定其进程的黏膜和全身免疫缺陷的既定和新兴治疗策略。
