系统性炎症反应介导慢加急性肝衰竭的研究进展

Advances in Research on the Role of Systemic Inflammatory in Mediating Acute-on-Chronic Liver Failure

摘要: 慢加急性肝衰竭(ACLF)指慢性肝病急剧恶化并出现功能障碍，是一种伴有肝内外器官衰竭、短期预后不佳的严重临床综合征。虽然目前发病机制尚未完全阐明，但可以明确系统性炎症反应与ACLF的起病和进展具有密切的关联。细菌感染、过量的酒精摄入以及嗜肝病毒活动可以释放病原相关分子模式和/或损伤相关分子模式激活炎症反应，损害重要脏器功能，诱导ACLF发生。疾病晚期由于炎症反应持续存在，先天性免疫细胞功能受抑难以抵御再发感染，病死率进一步升高。同时反应产生的炎性介质还将阻碍肝脏修复、改变血流动力学及线粒体功能加剧器官损伤。白介素22、间充质干细胞等新现的治疗方式可以改善炎症反应、降低感染风险、延缓病情进展，为部分患者后续接受肝移植治疗争取更多时间。针对系统性炎症作用于ACLF的诸多环节还有待进一步研究，开发更加有效的抗炎治疗手段也将提高患者生存率并缓解疾病负担。

Abstract: Acute-on-chronic liver failure (ACLF) is delineated as a rapid exacerbation of chronic hepatic disorders, culminating in functional impairment and is identified as a grave clinical syndrome characterized by both hepatic and extrahepatic organ failures, concomitant with a dismal short-term prognosis. The pathogenesis of ACLF, albeit not entirely elucidated, has been unequivocally associated with systemic inflammatory playing a pivotal role in its initiation and progression. The release of pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPs) triggered by bacterial infections, excessive alcohol consumption, and active hepatotropic viral infections activates inflammatory responses. This, in turn, inflicts damage upon major organs function, precipitating the onset of ACLF. In the advanced stages of the disease, the protracted presence of inflammatory responses leads to a suppression of innate immune cell functions, thereby impairing the host’s defense against recurrent infections and further escalating mortality rates. Concurrently, the inflammatory mediators impede hepatic regeneration, modify hemodynamics, and deteriorate mitochondrial function, thus exacerbating organ damage. Emerging therapeutic interventions, such as the administration of interleukin-22 and the employment of mesenchymal stem cells, have shown promise in ameliorating the inflammatory response, diminishing infection risks, and retarding disease progression, thereby extending the temporal window for potential liver transplantation in a subset of patients. The intricate involvement of systemic inflammation in the multifaceted progression of ACLF necessitates further investigation, with the aim of developing more efficacious anti-inflammatory therapeutic modalities to enhance patient survival rates and alleviate disease burden.