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Published on: January 31, 2018
Small Annexin V-Positive Platelet-Derived Microvesicles Affect Prognosis in Cirrhosis: A Longitudinal Study
Delphine Weil1,2, Vincent Di Martino1,2, Guillaume Mourey3
1Service d'Hépatologie, CHU Jean Minjoz, Besançon, France.
Introduction:
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.
Methods:
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.
Results:
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.
Discussion:
Decreased circulating small AV+ PMV levels are associated with significantly lower transplant-free survival in cirrhotic patients independently of MELD score and platelet counts.
Insights
Lower levels of small annexin V-positive platelet-derived microvesicles (AV+ PMVs) in cirrhotic patients indicate a higher risk of death or liver transplant. These findings are independent of MELD score and platelet counts.
Area of Science:
- Hepatology
- Vascular Biology
- Biomarkers
Background:
- Microvesicles (MVs) with procoagulant properties may contribute to cirrhosis complications and mortality.
- Platelet-derived MVs (PMVs) are implicated in liver disease progression.
Purpose of the Study:
- To investigate the association between plasma levels of different microvesicle types and transplant-free survival in cirrhotic patients.
- To evaluate the impact of microvesicles on the Model for End-Stage Liver Disease (MELD) score.
Main Methods:
- Quantified microvesicles (PMVs, endothelial-derived MVs, RBC-derived MVs) using flow cytometry in 90 cirrhotic patients and 10 healthy volunteers.
- Assessed the impact of microvesicle levels on 6-month transplant-free survival using log-rank tests and logistic regression.
Main Results:
- Circulating small annexin V-positive PMV (AV+ PMV) levels were lower in cirrhotic patients and inversely correlated with MELD scores.
- Patients with low baseline small AV+ PMV levels exhibited significantly lower 6-month transplant-free survival (72.6% vs 96.2%).
- Lower small AV+ PMV levels were associated with a 5- to 8-fold increased risk of death or liver transplant, independent of MELD score and other clinical factors.
Conclusions:
- Decreased circulating small AV+ PMV levels are a significant independent predictor of poor transplant-free survival in cirrhotic patients.
- These findings suggest small AV+ PMVs may serve as a prognostic biomarker in cirrhosis management.
