Service d'Hépatologie, CHU Jean Minjoz, Besançon, France.
EA 4266, Épigénétique des Infections Virales et des Maladies Inflammatoires EPILAB, Univ Bourgogne Franche-Comté, Besançon, France.
Clin Transl Gastroenterol. 2021 Apr 28;12(5):e00333. doi: 10.14309/ctg.0000000000000333.
Microvesicles (MVs) with procoagulant properties may favor liver parenchymal extinction, then cirrhosis-related complications and mortality. In a longitudinal cohort of cirrhotic patients, we measured plasma levels of platelet-derived MVs (PMVs), endothelial-derived MVs, and red blood cell-derived MVs, expressing phosphatidylserine (annexin V-positive [AV+]) or not, and evaluated their impact on Model for End-Stage Liver Disease (MELD) score and transplant-free survival.
MVs were quantified using flow cytometry in plasma from 90 noninfected cirrhotic patients and 10 healthy volunteers matched for age and sex. Impact of plasma microvesicle levels on 6-month transplant-free survival was assessed using log-rank tests and logistic regression.
Microvesicle levels, mostly platelet-derived, were 2.5-fold higher in healthy volunteers compared with cirrhotic patients. Circulating small AV+ PMV levels were lower in cirrhotic patients (P = 0.014) and inversely correlated with MELD scores (R = -0.28; P = 0.0065). During 1-year follow-up, 8 patients died and 7 underwent liver transplantation. In the remaining patients, circulating microvesicle levels did not change significantly. Six-month transplant-free survival was lower in patients with low baseline small AV+ PMV levels (72.6% vs 96.2%; P = 0.0007). In multivariate analyses adjusted for age, ascites, esophageal varices, encephalopathy, clinical decompensation, total platelet counts, MELD score, and/or Child-Pugh C stage, patients with lower small AV+ PMV levels had a significant 5- to 8-fold higher risk of 6-month death or liver transplant. Other PMV levels did not impact on survival.
Decreased circulating small AV+ PMV levels are associated with significantly lower transplant-free survival in cirrhotic patients independently of MELD score and platelet counts.
具有促凝特性的微小囊泡 (MVs) 可能有利于肝实质消失，进而导致肝硬化相关并发症和死亡率。在一项对肝硬化患者的纵向队列研究中，我们测量了血浆中血小板衍生的微小囊泡 (PMVs)、内皮衍生的微小囊泡和表达磷脂酰丝氨酸（ Annexin V 阳性 [AV+]）或不表达的红细胞衍生微小囊泡的水平，并评估了它们对终末期肝病模型评分 (MELD) 和无移植存活率的影响。
使用流式细胞术在 90 名未感染的肝硬化患者和 10 名年龄和性别匹配的健康志愿者的血浆中定量微小囊泡。使用对数秩检验和逻辑回归评估血浆微小囊泡水平对 6 个月无移植存活率的影响。
与肝硬化患者相比，健康志愿者的微小囊泡水平（主要是血小板衍生的）高 2.5 倍。肝硬化患者循环中的小 AV+ PMV 水平较低（P = 0.014），与 MELD 评分呈负相关（R = -0.28；P = 0.0065）。在 1 年的随访期间，有 8 名患者死亡，7 名患者接受了肝移植。在其余患者中，循环中小 AV+ PMV 水平没有明显变化。小 AV+ PMV 水平较低的患者 6 个月无移植存活率较低（72.6%与 96.2%；P = 0.0007）。在调整年龄、腹水、食管静脉曲张、脑病、临床失代偿、总血小板计数、MELD 评分和/或 Child-Pugh C 期后进行的多变量分析中，小 AV+ PMV 水平较低的患者在 6 个月内死亡或肝移植的风险显著增加 5-8 倍。其他 PMV 水平对存活率没有影响。
循环中小 AV+ PMV 水平降低与肝硬化患者的无移植存活率显著降低相关，独立于 MELD 评分和血小板计数。
