Microvesicles and Monocytes to Predict Mortality of Patients with Cirrhosis

NCT03837444 | Completed

• 1 other identifier: D20180152
• Study Type: observational
• Target: 335
• Locations: 1 country
• Sites: 5

Brief Summary

Chronic liver diseases related to viral hepatitis, metabolic syndrome or excessive alcohol consumption can evolve towards cirrhosis. Cirrhosis is responsible for 170 000 deaths per year in Europe. Initially asymptomatic and called "compensated" it can become "decompensated" with the developement of acute complications such as infections, ascites or variceal bleeding. The transition from compensated to decompensated cirrhosis is associated with a reduction in survival from 95 to 55% at 1 year. The only curative treatment for cirrhosis is liver transplantation (LT). Liver transplants are allocated according to the severity of the patients. Despite a modest prognostic value (area under the ROC curve = 0.7 to predict the risk of death), graft allocation is based on the MELD (Model for End-Stage Liver Disease) score including INR, bilirubin and serum creatinine. In 2014, 11.5% of registered patients died on the liver transplant waiting list, illustrating the need for biomarkers that predict death and improve MELD-based prediction. Microvesicles are membrane vesicles released in extracellular space during cell activation or apoptosis. Our team showed that circulating levels of hepatocyte microvesicles increase with the severity of cirrhosis and predict survival at 6 months independently of MELD score in a cohort of 242 patients with cirrhosis. Type 1 interferons (IFN-1) are mediators of inflammation, which is excessively activated in cirrhosis. Our team has shown that a gene signature (IFN score) measured in the immune cells of 101 patients with cirrhosis is able to predict 6 month-survival independently of the MELD score. Thus, the investigators hypothesize that a composite score combining the level of circulating hepatocyte microvesicles, the IFN score and the MELD score could improve the prediction of survival in patients with severe cirrhosis. The aim of this study is to compare the prognostic performance for the cumulative incidence of death at 6 months of a composite score including MELD, hepatocyte microvesicle level and IFN score with that of the MELD score alone, in patients with Child B or C cirrhosis, considering liver transplantation as a competitive risk. To address this question, peripheral blood from 335 patients with Child B or C cirrhosis will be obtained and hepatocyte microvesicle levels and IFN score will be measured using ELISA/filtration and Real Time-quantitative PCR.

Conditions

Cirrhosis

Keywords

Cirrhosis; Outcome prognostication; Microvesicle; Monocyte

Outcome Measures

Primary Outcomes (1)

• Compare the prognostic performance for the cumulative incidence of death at 6 months of a composite score including MELD, hepatocyte microvesicle concentration and IFN score to that of the MELD alone, considering LT as a competitive risk

  AUROC of the composite score including MELD, hepatocyte microvesicle and IFN score for predicting the cumulative incidence of death at 6 months (considering liver transplantation (LT) as a competitive risk) compared to the AUROC of the MELD score alone

  6 months

Secondary Outcomes (16)

• Compare the prognostic performance for the cumulative incidence of death at 12 months of a composite MELD-microvesicles-IFN score to that of the MELD alone, considering liver transplantation as a competitive risk

  12 months

• Compare the prognostic performance for the cumulative incidence of death post-LT, of the composite MELD-microvesicles-IFN score to that of the MELD alone, in patients with Child B or C cirrhosis transplanted during the 12 months following the inclusion

  One month post LT

• Compare the prognostic performance for episodes of "Acute on Chronic Liver Failure", of the composite MELD-microvesicles-IFN score to the MELD score alone, considering LT and death as competitive risks at 6 and 12 months

  6 months and 12 months

• Determine whether this composite score improves prediction of the cumulative incidence of death of patients with Child B or C cirrhosis, compared to the MELD score alone, using the continuous version of the Net Reclassification Index (NRI)

  6 months and 12 months

• Compare the prognostic performance for the cumulative incidence of death of a MELD-microvesicles-IFN score to that of the MELD-Na score, considering LT as a competitive event at 6 and 12 months

  6 months and 12 months

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients aged over 18 and under 90 with stable Child B or C cirrhosis

You may qualify if:

• Age between 18 and 90 years
• Child-Pugh B or Child-Pugh C cirrhosis diagnosed on the basis of one or several of the following elements :
• Liver Biopsy
• Liver stiffness\>15kPa measured by Fibroscan
• Combination of clinical, laboratory and imaging criteria characteristic of cirrhosis (association of signs of portal hypertension, liver failure and abnormal liver morphology in a patient with at least one cause of cirrhosis)

You may not qualify if:

• Alcoholic hepatitis in the previous month
• History of porto-systemic shunt or liver transplant
• Primary sclerosing cholangitis
• Primary biliary cirrhosis
• Budd-Chiari Syndrome
• Hepatocellular carcinoma outside the Milan criteria contraindicating transplantation
• Active extrahepatic neoplasia
• HIV or known immune deficiency or immunosuppressive treatment
• Pregnant or breastfeeding woman
• Protected populations: persons under guardianship or curatorship
• Patient not affiliated to social security
• Patient who did not signed consent
• Ongoing participation in an intervention research whose protocol could, according to the literature, modify the release of hepatocyte microvesicles or the IFN score

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (5)

Avicenne Hospital

Bobigny, France

Location

Beaujon hospital

Clichy, France

Location

La Pitié Salpêtrière hospital

Paris, France

Location

De La Fontaine hospital

Saint-Denis, France

Location

Foch hospital

Suresnes, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and RNA

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Emmanuel WEISS, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 12, 2019
• Study Start: June 12, 2019
• Primary Completion: July 5, 2023
• Study Completion: February 29, 2024
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)