Albumin in decompensated cirrhosis: new concepts and perspectives
Albumin in decompensated cirrhosis: new concepts and perspectives
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DOI：
10.1136/gutjnl-2019-318843
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发表时间：
2020-06-01
期刊：
影响因子：
24.5
通讯作者：
Arroyo, Vicente
中科院分区：
文献类型：
--
作者：
Bernardi, Mauro;Angeli, Paolo;Arroyo, Vicente
失代偿性肝硬化的病理生理学背景的特点是全身性促炎和促氧化环境，在多器官功能障碍的发展中起着重要作用。这种异常主要是由于来自肠道的细菌和/或细菌产物的全身性传播以及来自患病肝脏的炎症相关分子模式通过激活免疫细胞触发促炎介质的释放。这些过程的恶化是慢加急性肝衰竭发展的基础。促进多器官功能障碍和衰竭的另一机制可能与引起全身细胞能量危机的线粒体氧化磷酸化功能障碍有关。失代偿性肝硬化患者的全身促炎和促氧化状态也是白蛋白分子结构和功能变化的原因，这破坏了其多效性非肿瘤性质，如抗氧化、清除、免疫调节和内皮保护功能。这些异常的知识为机械治疗提供了新的靶点。在这方面，白蛋白的粘附和非粘附特性使其成为一种潜在的多靶点药物。这将扩大白蛋白在失代偿性肝硬化中使用的明确适应症，其主要目的是改善有效血容量或预防其恶化。最近有证据表明，肝硬化和腹水患者长期给予白蛋白可提高生存率、预防并发症、简化腹水管理并减少住院治疗。然而，不同的结果表明，需要进一步研究，旨在确认白蛋白的有益作用，阐明其最佳剂量和给药方案，并确定从长期白蛋白给药中获益最大的患者。
The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.