Department of Biomedicine, University of Basel, Switzerland; University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland.
Laboratory of Hepatology, Department of Chronic Diseases, Metabolism and aging (CHROMETA), University of Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospital Gasthuisberg, Leuven, Belgium.
J Hepatol. 2020 Jul;73(1):186-201. doi: 10.1016/j.jhep.2020.03.027. Epub 2020 Mar 30.
Cirrhosis is a multisystemic disease wherein inflammatory responses originating from advanced liver disease and its sequelae affect distant compartments. Patients with cirrhosis are susceptible to bacterial infections, which may precipitate acute decompensation and acute-on-chronic liver failure, both of which are associated with high short-term mortality. Innate immune cells are an essential first line of defence against pathogens. Activation of liver macrophages (Kupffer cells) and resident mastocytes generate proinflammatory and vaso-permeating mediators that induce accumulation of neutrophils, lymphocytes, eosinophils and monocytes in the liver, and promote tissue damage. During cirrhosis progression, damage- and pathogen-associated molecular patterns activate immune cells and promote development of systemic inflammatory responses which may involve different tissues and compartments. The antibacterial function of circulating neutrophils and monocytes is gradually and severely impaired as cirrhosis worsens, contributing to disease progression. The mechanisms underlying impaired antimicrobial responses are complex and incompletely understood. This review focuses on the continuous and distinct perturbations arising in innate immune cells during cirrhosis, including their impact on disease progression, as well as reviewing potential therapeutic targets.
肝硬化是一种多系统疾病，其起源于晚期肝病及其后果的炎症反应会影响到远处的组织。肝硬化患者易发生细菌感染，这可能会导致急性失代偿和慢加急性肝衰竭，这两者都与短期高死亡率相关。先天免疫细胞是抵御病原体的第一道防线。肝脏巨噬细胞（枯否细胞）和固有肥大细胞的激活会产生促炎和血管通透的介质，导致中性粒细胞、淋巴细胞、嗜酸性粒细胞和单核细胞在肝脏内积聚，并促进组织损伤。在肝硬化进展过程中，损伤相关和病原体相关的分子模式会激活免疫细胞，并促进全身炎症反应的发展，这可能涉及不同的组织和部位。随着肝硬化的恶化，循环中性粒细胞和单核细胞的抗菌功能逐渐严重受损，这有助于疾病的进展。导致抗菌反应受损的机制很复杂，目前尚未完全了解。这篇综述重点介绍了肝硬化过程中先天免疫细胞持续且明显的紊乱，包括它们对疾病进展的影响，并回顾了潜在的治疗靶点。
