Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy.
Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy; Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA; Section of Digestive Diseases, VA Connecticut Healthcare System, West Haven, CT, USA.
J Hepatol. 2018 May;68(5):949-958. doi: 10.1016/j.jhep.2017.12.027. Epub 2018 Jan 10.
BACKGROUND & AIMS: The main stages of cirrhosis (compensated and decompensated) have been sub-staged based on clinical, endoscopic, and portal pressure (determined by the hepatic venous pressure gradient [HVPG]) features. Vasodilation leading to a hyperdynamic circulatory state is central in the development of a late decompensated stage, with inflammation currently considered a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation (by C-reactive protein [CRP]) among the different sub-stages of cirrhosis and to investigate their interrelationship and prognostic relevance.
A single center, prospective cohort of patients with cirrhosis undergoing per protocol hepatic and right-heart catheterization and CRP measurement, were classified into recently defined prognostic stages (PS) of compensated (PS1: HVPG ≥6 mmHg but <10 mmHg; PS2: HVPG ≥10 mmHg without gastroesophageal varices; PS3: patients with gastroesophageal varices) and decompensated (PS4: diuretic-responsive ascites; PS5: refractory ascites) disease. Cardiodynamic states based on cardiac index (L/min/m) were created: relatively hypodynamic (<3.2), normodynamic (3.2-4.2) and hyperdynamic (>4.2).
Of 238 patients, 151 were compensated (PS1 = 25; PS2 = 36; PS3 = 90) and 87 were decompensated (PS4 = 48; PS5 = 39). Mean arterial pressure decreased progressively from PS1 to PS5, cardiac index increased progressively from PS1-to-PS4 but decreased in PS5. HVPG, model for end-stage liver disease (MELD), and CRP increased progressively from PS1-to-PS5. Among compensated patients, age, HVPG, relatively hypodynamic/hyperdynamic state and CRP were predictive of decompensation. Among patients with ascites, MELD, relatively hypodynamic/hyperdynamic state, post-capillary pulmonary hypertension, and CRP were independent predictors of death/liver transplant.
Our study demonstrates that, in addition to known parameters, cardiopulmonary hemodynamics and CRP are predictive of relevant outcomes, both in patients with compensated and decompensated cirrhosis.
There are two main stages in cirrhosis, compensated and decompensated, each with a main relevant outcome. In compensated cirrhosis the main relevant outcome is the development of ascites, while in decompensated cirrhosis it is death. Major roles of cardiac dysfunction and systemic inflammation have been hypothesized in the evolution of the disease in decompensated patients. In this study, we have shown that these factors were also involved in the progression from compensated to decompensated stage.
根据临床、内镜和门脉压力(由肝静脉压力梯度[HVPG]确定)特征,对肝硬化(代偿期和失代偿期)的主要阶段进行了亚分期。导致高动力循环状态的血管舒张在晚期失代偿阶段的发展中起着核心作用,炎症目前被认为是关键驱动因素。我们旨在评估肝硬化不同亚分期的肝/全身血液动力学和炎症(通过 C 反应蛋白[CRP]),并研究它们之间的相互关系及其预后相关性。
本研究为单中心前瞻性队列研究,纳入了接受协议规定的肝和右心导管检查以及 CRP 测量的肝硬化患者,根据最近定义的预后分期(PS)进行分组:代偿期(PS1:HVPG≥6mmHg 但<10mmHg;PS2:HVPG≥10mmHg 且无胃食管静脉曲张;PS3:有胃食管静脉曲张的患者)和失代偿期(PS4:利尿剂反应性腹水;PS5:难治性腹水)。根据心指数(L/min/m)创建心动力学状态:相对低动力(<3.2)、正常动力(3.2-4.2)和高动力(>4.2)。
共纳入 238 例患者,其中 151 例为代偿期(PS1=25 例;PS2=36 例;PS3=90 例),87 例为失代偿期(PS4=48 例;PS5=39 例)。从 PS1 到 PS5,平均动脉压逐渐下降,心指数从 PS1 到 PS4 逐渐升高,但在 PS5 下降。HVPG、终末期肝病模型(MELD)和 CRP 从 PS1 到 PS5 逐渐升高。在代偿期患者中,年龄、HVPG、相对低动力/高动力状态和 CRP 是失代偿的预测因素。在腹水患者中,MELD、相对低动力/高动力状态、毛细血管后肺动脉高压和 CRP 是死亡/肝移植的独立预测因素。
本研究表明,除了已知的参数外,心肺血液动力学和 CRP 可预测代偿期和失代偿期肝硬化患者的相关结局。