管理失代偿期肝硬化的新视角

StephenW

Novel perspectives in the management of decompensated cirrhosis

    Mauro Bernardi & Paolo Caraceni

Nature Reviews Gastroenterology & Hepatologyvolume 15, pages753–764 (2018) | Download Citation
Abstract

The current approaches to the management of patients with decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. The improved knowledge of the pathophysiological background of advanced cirrhosis, represented by a sustained systemic inflammation strictly linked to a circulatory dysfunction, provides a novel paradigm for the management of these patients, with the ambitious target of modifying the course of the disease by preventing the onset of complications and multiorgan failure; these interventions will eventually improve patients’ quality of life, prolong survival and reduce health-care costs. Besides aetiological treatments, these goals could be achieved by persistently antagonizing key pathophysiological events, such as portal hypertension, abnormal bacterial translocation from the gut, liver damage, systemic inflammation, circulatory dysfunction and altered immunological responses. Interestingly, in addition to strategies based on new therapeutic agents, these targets can be tackled by employing drugs that are already used in patients with cirrhosis for different indications or in other clinical settings, including non-absorbable oral antibiotics, non-selective β-blockers, human albumin and statins. The scope of the present Review includes reporting updated information on the treatments that promise to influence the course of advanced cirrhosis and thus act as disease-modifying agents.
Key points

    The management of decompensated cirrhosis currently addresses the prevention or treatment of specific complications; disease-modifying agents able to modify the course of decompensated cirrhosis still represent an unmet need.

    Removing aetiological factors can halt the progression of chronic liver disease, yet a substantial portion of patients with decompensated cirrhosis do not benefit from even successful aetiological treatments.

    Portal hypertension, abnormal translocation of bacterial products from the gut (‘upstream’ events) and the consequent systemic inflammation and circulatory dysfunction (‘downstream’ events) represent the main targets for mechanistic approaches.

    Transjugular portosystemic shunt and non-selective β-blockers can be seen as upstream treatments, as they lower portal hypertension and might prevent bacterial translocation.

    Bacterial translocation can be antagonized by antibiotic-based and non-antibiotic-based interventions, but the former entail the risk of antibiotic resistance, whereas the efficacy of the latter still needs to be demonstrated.

    Human albumin and statins, which are able to simultaneously target several downstream pathophysiological mechanisms, represent promising disease-modifying agents, as they have proved their efficacy in prospective randomized trials.

StephenW

管理失代偿期肝硬化的新视角

    Mauro Bernardi和Paolo Caraceni

Nature Reviews Gastroenterology＆Hepatologyvolume 15，pages753-764（2018）|下载引文
抽象

目前用于治疗失代偿性肝硬化患者的方法基于旨在预防或治疗该疾病的特定并发症的靶向策略。以与循环功能障碍严格相关的持续全身性炎症为代表的晚期肝硬化的病理生理学背景的改进知识为这些患者的管理提供了新的范例，其雄心勃勃的目标是通过预防发病来改变疾病的进程。并发症和多器官衰竭;这些干预措施最终将改善患者的生活质量，延长生存期并降低医疗保健成本。除了病原学治疗外，这些目标可以通过持续拮抗关键的病理生理事件来实现，例如门静脉高压症，肠道异常细菌移位，肝损伤，全身性炎症，循环功能障碍和改变的免疫反应。有趣的是，除了基于新治疗药物的策略之外，这些目标可以通过使用已经用于肝硬化患者的药物来解决，用于不同的适应症或其他临床环境，包括不可吸收的口服抗生素，非选择性β受体阻滞剂，人白蛋白和他汀类药物。本评价的范围包括报告有关影响晚期肝硬化病程的治疗方法的最新信息，从而充当疾病调节剂。
关键点

    失代偿期肝硬化的管理目前涉及特定并发症的预防或治疗;能够改变失代偿性肝硬化病程的疾病调节剂仍然代表着未满足的需求。

    去除病因可以阻止慢性肝病的进展，但是大部分失代偿性肝硬化患者甚至没有从成功的病因治疗中获益。

    门静脉高压症，肠道细菌产物的异常转移（“上游”事件）以及随后的全身性炎症和循环功能障碍（“下游”事件）代表了机械方法的主要目标。

    经颈静脉门体分流术和非选择性β受体阻滞剂可视为上游治疗，因为它们可降低门静脉高压并可能阻止细菌移位。

    基于抗生素和非抗生素的干预可以拮抗细菌移位，但前者需要抗生素抗性的风险，而后者的功效仍需要证明。

    能够同时靶向几种下游病理生理机制的人白蛋白和他汀类药物代表了有希望的疾病调节剂，因为它们已经在前瞻性随机试验中证明了它们的功效。