靶向肠肝免疫轴治疗肝硬化

StephenW

Targeting the gut-liver-immune axis to treat cirrhosis

    http://orcid.org/0000-0001-9290-3044Thomas Henry Tranah1, http://orcid.org/0000-0002-8222-4555Lindsey A Edwards1, Bernd Schnabl2, http://orcid.org/0000-0001-6133-4619Debbie Lindsay Shawcross1

Author affiliations

    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

    Correspondence to Professor Debbie Lindsay Shawcross, Institute of Liver Studies and Transplantation, King's College London, London WC2R 2LS, UK; [email protected]

Abstract

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.
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http://dx.doi.org/10.1136/gutjnl-2020-320786

StephenW

靶向肠肝免疫轴治疗肝硬化

    http://orcid.org/0000-0001-9290-3044Thomas Henry Tranah1，http://orcid.org/0000-0002-8222-4555Lindsey A Edwards1，Bernd Schnabl2，http://orcid.org/0000-0001 -6133-4619黛比·林赛·肖克罗斯1

作者单位

    伦敦国王学院，伦敦生命科学学院，免疫学和微生物科学学院，炎症生物学系，肝生物学研究所
    加利福尼亚大学圣地亚哥分校医学系，美国加利福尼亚州圣地亚哥

    与英国伦敦国王学院肝病研究和移植研究所Debbie Lindsay Shawcross教授的通讯，英国WC2R 2LS； [email protected]

抽象

肝硬化性门静脉高压症的特点是发生腹水，脑病，门脉高压性出血和肝肾综合征的代偿失调事件，这些失调事件发生在与肝硬化相关的免疫功能障碍（CAID）的背景下，并定义了发病率和预后。 CAID描述了二分法观察结果，即系统免疫细胞被引发并表现出炎症表型，而未能引起对病原体攻击的强烈反应。细菌感染，包括自发性细菌性腹膜炎，是晚期慢性肝病的常见并发症，可引起静脉曲张出血，肝肾综合征和慢性肝衰竭。它们通常来自肠道来源的生物，并与晚期慢性肝病中共生肠道菌群的营养不良密切相关。

在这里，我们审查了在慢性慢性肝病的背景下发生的肝硬化性肝病，肠屏障功能障碍和宿主-微生物组区室化和黏膜免疫同调缺乏之间的联系。我们讨论已建立的和新兴的治疗策略，旨在恢复小肠肝病，增强肠道屏障功能，改善表征和定义失代偿性肝硬化病程的粘膜和全身免疫缺陷。
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http://dx.doi.org/10.1136/gutjnl-2020-320786