Zaccherini G, Bernardi M
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Acta Gastroenterol Belg. 2019 Apr-Jun;82(2):301-308.
Low serum albumin is common in cirrhosis and is associated with a reduced survival. Moreover, in this setting, the native isoform of albumin can be severely reduced due to several posttranscriptional changes that impair the non-oncotic properties of the molecule. Due to its oncotic power, albumin acts as a powerful plasma expander. As such, it can antagonize the consequences of effective hypovolemia deriving from the systemic hemodynamics abnormalities that characterize advanced cirrhosis. Indeed, the current established indications to the use of albumin in this context pertain to conditions deriving from an acute drop of effective volemia. Recent advances have shown that the pathophysiological background of decompensated cirrhosis is characterized by a sustained systemic inflammatory and pro-oxidant state deriving by an abnormal bacterial translocation from the gut. These abnormalities ultimately lead to the multiorgan dysfunction. In this cascade of events, long-term albumin administration could act against several pathogenic factors through its non-oncotic properties, thus representing a potential multi-target mechanistic treatment. Over the last year, two randomized clinical trials on this topic were published. The ANSWER Trial demonstrated that the long-term albumin administration in patients with decompensated cirrhosis improves overall survival, reduces the incidence of complications and the need of hospitalizations and ameliorates the quality of life, being cost-effective. The MACHT trial challenged these results, but the differences between the two studies (sample size, baseline severity of cirrhosis, length of follow-up and amount of albumin administered) could explain its variant results, providing the basis for further insights into this matter.
低血清白蛋白在肝硬化中很常见,且与生存率降低有关。此外,在这种情况下,由于多种转录后变化损害了白蛋白分子的非胶体渗透压特性,其天然异构体可能会严重减少。由于其胶体渗透压作用,白蛋白可作为一种强大的血浆扩容剂。因此,它可以对抗晚期肝硬化特征性全身血流动力学异常所导致的有效血容量减少的后果。事实上,目前在这种情况下使用白蛋白的既定指征适用于因有效血容量急性下降而产生的情况。最近的进展表明,失代偿期肝硬化的病理生理背景的特征是肠道细菌异常移位导致持续的全身炎症和促氧化状态。这些异常最终导致多器官功能障碍。在这一系列事件中,长期给予白蛋白可以通过其非胶体渗透压特性对抗多种致病因素,从而代表一种潜在的多靶点机制性治疗方法。在过去一年中,发表了两项关于该主题的随机临床试验。ANSWER试验表明,对失代偿期肝硬化患者长期给予白蛋白可提高总体生存率,降低并发症发生率和住院需求,并改善生活质量,且具有成本效益。MACHT试验对这些结果提出了质疑,但两项研究之间的差异(样本量、肝硬化的基线严重程度、随访时间和白蛋白给药量)可以解释其不同的结果,为进一步深入研究此事提供了依据。