Abstract：
Chronic liver disease (CLD) leads to hepatocellular injury that triggers a pro-inflammatory state in several parenchymal and non-parenchymal hepatic cell types ultimately resulting in liver fibrosis, cirrhosis, portal hypertension (PH) and liver failure. Thus, an improved understanding of the inflammasomes - as key molecular drivers of liver injury - supports the development of novel diagnostic or prognostic biomarkers and effective therapeutics. In liver disease, innate immune cells respond to hepatic noxes by activating cell-intrinsic inflammasomes via toll-like receptors (TLRs) and nuclear factor kappa-B (NF-κB) and release of pro-inflammatory cytokines (such as IL-1β, IL-18, TNF-α and IL-6). Subsequently, cells of the adaptive immune system are recruited to fuel hepatic inflammation, and liver parenchymal cells may undergo programmed cell-death mediated by gasdermin D, termed pyroptosis. With liver disease progression, there is a shift towards a type 2 inflammatory response, which promotes tissue repair but also fibrogenesis. Inflammasome activation may also occur at extrahepatic sites, such as the white adipose tissue in metabolic dysfunction-associated steatohepatitis (MASH). In end-stage liver disease, flares of inflammation (e.g., in severe alcohol-related hepatitis) that spark on a dysfunctional immune system, contribute to inflammasome-mediated liver injury and potentially result in organ dysfunctions/failures, as seen in acute-on-chronic liver failure (ACLF). This review provides an overview on current concepts regarding inflammasome activation in liver disease progression and related biomarkers and therapeutic approaches that are being developed for patients with liver disease.
摘要：
慢性肝病（CLD）导致肝细胞损伤，在几种实质和非实质肝细胞类型中引发促炎状态，最终导致肝纤维化，肝硬化,门静脉高压症（PH）和肝功能衰竭。因此，对炎性体-肝损伤的关键分子驱动因素-的进一步理解支持了新型诊断或预后生物标志物和有效治疗方法的开发.在肝脏疾病中，先天免疫细胞通过Toll样受体（TLRs）和核因子κB（NF-κB）激活细胞内的炎性小体并释放促炎细胞因子（例如IL-1β，IL-18、TNF-α和IL-6)。随后，适应性免疫系统的细胞被招募来助长肝脏炎症，肝实质细胞可能经历由gasderminD介导的程序性细胞死亡，称为焦亡。随着肝脏疾病的进展，向2型炎症反应转变，促进组织修复，也促进纤维发生。炎症体激活也可能发生在肝外部位，如代谢功能障碍相关脂肪性肝炎（MASH）的白色脂肪组织。在终末期肝病中，炎症的耀斑(例如，在严重的酒精相关性肝炎中）会激发功能失调的免疫系统，有助于炎症小体介导的肝损伤，并可能导致器官功能障碍/衰竭，如在急性对慢性肝衰竭（ACLF）中所见。这篇综述概述了当前关于肝脏疾病进展中炎性小体激活的概念以及正在为肝病患者开发的相关生物标志物和治疗方法。
