Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece.
Med Hypotheses. 2011 Sep;77(3):419-23. doi: 10.1016/j.mehy.2011.05.034. Epub 2011 Jun 23.
Patients with liver cirrhosis are prone to serious complications by almost all systems, leading to high morbidity rates and even death. Although the functional and structural derangement of diverse vital organs developed in the course of advanced liver disease is the result of one entity (cirrhosis) there are various treatment modalities for each system's complications, which are often ineffective. Identification of the link which connects the complications of cirrhosis from diverse systems might lead to a global, simple and more effective treatment approach for patients with cirrhosis. Accumulating evidence from experimental and clinical studies suggests that intestinal barrier dysfunction and subsequent gut-derived endotoxemia represent an important common pathogenetic mechanism in the development of diverse complications of cirrhosis. Intestinal oxidative stress seems to be a pivotal factor of gut barrier dysfunction in cirrhosis through promotion of enterocyte apoptosis, modulation of intestinal tight junctions and impairment of intestinal brush border function. In parallel, oxidative stress plays a fundamental role in the aggravation of liver injury and in the structural and/or functional derangements of diverse organs complicating the course of cirrhosis. Our hypothesis is that antioxidant treatments could prevent in a global way virtually all cirrhosis-related complications acting in two crucial levels in the pathophysiological cascade of events: (a) in a primary level, which is the gut-liver axis by ameliorating gut-derived endotoxemia, through prevention of intestinal oxidative stress and its associated gut barrier dysfunction, concurrently conferring direct antioxidant protection in the liver tissue and (b) in a secondary level, which refers to the diverse organs whose function is affected by liver cirrhosis, by preventing their oxidant-related structural and functional derangements.
肝硬化患者几乎会因所有系统出现严重并发症，导致高发病率甚至死亡。尽管在晚期肝病过程中发生的各种重要器官的功能和结构紊乱是一个实体（肝硬化）的结果，但针对每个系统的并发症有多种治疗方法，这些方法往往无效。确定将肝硬化的各种系统并发症联系起来的环节，可能为肝硬化患者提供一种整体、简单且更有效的治疗方法。来自实验和临床研究的大量证据表明，肠道屏障功能障碍和随后的肠道内毒素血症代表了肝硬化多种并发症发展中的一个重要共同发病机制。肠道氧化应激似乎是肝硬化中肠屏障功能障碍的关键因素，通过促进肠上皮细胞凋亡、调节肠道紧密连接和损害肠刷状缘功能来实现。同时，氧化应激在加重肝损伤以及在肝硬化病程中并发的各种器官的结构和/或功能紊乱中起着根本作用。我们的假设是，抗氧化治疗可以通过在两个关键水平上预防几乎所有与肝硬化相关的并发症，从而达到全面的效果：（a）在初级水平，即通过改善肠道来源的内毒素血症，改善肠道-肝脏轴，通过预防肠道氧化应激及其相关的肠道屏障功能障碍，同时在肝组织中提供直接的抗氧化保护；（b）在二级水平，即通过预防受肝硬化影响的各种器官的氧化相关结构和功能紊乱。
