Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia.
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Front Immunol. 2019 Feb 25;10:293. doi: 10.3389/fimmu.2019.00293. eCollection 2019.
Liver cirrhosis is an increasing health burden and public health concern. Regardless of etiology, patients with cirrhosis are at risk of a range of life-threatening complications, including the development of infections, which are associated with high morbidity and mortality and frequent hospital admissions. The term Cirrhosis-Associated Immune Dysfunction (CAID) refers to a dynamic spectrum of immunological perturbations that develop in patients with cirrhosis, which are intimately linked to the underlying liver disease, and negatively correlated with prognosis. At the two extremes of the CAID spectrum are systemic inflammation, which can exacerbate clinical manifestations of cirrhosis such as hemodynamic derangement and kidney injury; and immunodeficiency, which contributes to the high rate of infection in patients with decompensated cirrhosis. Innate immune cells, in particular monocytes/macrophages and neutrophils, are pivotal effector and target cells in CAID. This review focuses on the pathophysiological mechanisms leading to impaired innate immune function in cirrhosis. Knowledge of the phenotypic manifestation and pathophysiological mechanisms of cirrhosis associated immunosuppression may lead to immune targeted therapies to reduce susceptibility to infection in patients with cirrhosis, and better biomarkers for risk stratification, and assessment of efficacy of novel immunotherapies.
肝硬化是一个日益严重的健康负担和公共卫生问题。无论病因如何，肝硬化患者都有一系列危及生命的并发症的风险，包括感染的发生，这与高发病率和死亡率以及频繁住院有关。术语“肝硬化相关免疫功能障碍（CAID）”是指肝硬化患者中发生的一系列免疫紊乱，与潜在的肝脏疾病密切相关，并与预后呈负相关。在 CAID 谱的两个极端是全身炎症，它可以加重肝硬化的临床表现，如血流动力学紊乱和肾脏损伤；以及免疫缺陷，这导致代偿性肝硬化患者感染率高。先天免疫细胞，特别是单核细胞/巨噬细胞和中性粒细胞，是 CAID 中的关键效应和靶细胞。这篇综述重点介绍了导致肝硬化时固有免疫功能受损的病理生理机制。对肝硬化相关免疫抑制的表型表现和病理生理机制的认识，可能导致针对免疫的治疗方法来降低肝硬化患者感染的易感性，并改善风险分层的生物标志物，以及评估新型免疫疗法的疗效。
