Liver Diseases
Conditions
Keywords
liver decompensation, extracellular vesicles, hepatocellular carcinoma, cirrhosis
Brief summary
Worldwide, cirrhosis is responsible for 2 million deaths per year. Hepatocellular carcinoma (HCC) accounts for 800,000 of these deaths and is the 3rd leading cause of cancer related death. Cirrhosis affects mainly a working age population, hence its heavy economic burden.While patients with compensated cirrhosis do not have symptoms and have a 10-year life expectancy, decompensation of cirrhosis heralds a dramatic decrease in life expectancy to 2 years. Biomarkers allowing reliable estimation of the risk for decompensation of cirrhosis would allow community-based care, possibly by nurse practitioners, of patients at low risk, while patients had high risk could be managed in secondary and tertiary care centers and included in clinical trials. Because HCC is usually asymptomatic at early stages, when it is still curable, it can easily be missed. Biomarkers allowing stratification of the risk of HCC would allow reinforced surveillance (using magnetic resonance imaging) of high-risk patients, and their inclusion in chemoprevention clinical trials. LIVER-TRACK aims at reliably predicting the outcome of patients with compensated cirrhosis through the development of a Tests for Decompensation and a Test for HCC. This will be achieved through leveraging circulating extracellular vesicles (EVs), an untapped source of biomarkers in liver diseases, as prognostic indicators, and combining them with existing blood biomarkers and single-nucleotide polymorphisms (SNPs). LIVER-TRACK also aims at delivering technologies for EV measurement that are useable in medical practice.
Detailed description
Worldwide, cirrhosis is responsible for 2 million deaths per year. Hepatocellular carcinoma (HCC) accounts for 800,000 of these deaths and is the 3rd leading cause of cancer related death. Cirrhosis affects mainly a working age population, hence its heavy economic burden. While patients with compensated cirrhosis do not have symptoms and have a 10-year life expectancy, decompensation of cirrhosis heralds a dramatic decrease in life expectancy to 2 years. Biomarkers allowing reliable estimation of the risk for decompensation of cirrhosis would allow community-based care, possibly by nurse practitioners, of patients at low risk, while patients had high risk could be managed in secondary and tertiary care centers and included in clinical trials. Because HCC is usually asymptomatic at early stages, when it is still curable, it can easily be missed. Biomarkers allowing stratification of the risk of HCC would allow reinforced surveillance (using magnetic resonance imaging) of high-risk patients, and their inclusion in chemoprevention clinical trials. LIVER-TRACK aims at reliably predicting the outcome of patients with compensated cirrhosis through the development of a Tests for Decompensation and a Test for HCC. This will be achieved through leveraging circulating extracellular vesicles (EVs), an untapped source of biomarkers in liver diseases, as prognostic indicators, and combining them with existing blood biomarkers and single-nucleotide polymorphisms (SNPs). LIVER-TRACK also aims at delivering technologies for EV measurement that are useable in medical practice. LIVER-TRACK outputs are expected to: i) improve care for individual patients at highest medical need, i.e., patients with cirrhosis with high risk of decompensation or HCC; ii) decrease cirrhosis burden for public health, iii) facilitate drug development; and iv) technically allow exploitation of EVs as biomarkers in clinical practice, an obligatory step permitting expansion to other fields such as cancer and cardiovascular diseases.
Interventions
OTHERblood sampling for volunteers
A 38.5 ml blood sample will be taken to test for research taken to test for research
OTHERblood sampling for diabetics patients with F3/F4 fibrosis
32.5 ml will be sampled at inclusion, at one year visit and two year visit
OTHERblood sampling for patients with liver disease
A blood sample of 35.5 mL maximum will be taken for research purposes at the inclusion visit, M1 visit and M3 visit.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Volunteers without liver disease \- Inclusion criteria: Major
Exclusion criteria
* Known liver disease * Active cancer * Viral or bacterial infection within 2 weeks of inclusion (respiratory, dermatological, urinary, digestive, etc.) * Transfusion in the month preceding inclusion * Current participation or less than 3 months' participation in a therapeutic interventional trial * Absence of signed informed consent * Not affiliated to a social security scheme * Pregnant women * Person under guardianship or trusteeship Diabetic patients with F3/F4 fibrosis recruited and followed prospectively Inclusion criteria: * Patient aged 18 or over * Type 2 diabetic (ADA/WHO criteria recalled in section 20.5) * Hepatic fibrosis stage F3/F4 on liver biopsy or hepatic elasticity \> 10 kPa
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decompensation Test in patients with cirrhosis | 48 months after the beginning of the project | The discriminating power of the Decompensation Test will be measured using the C-index |
| HCC Test in patients with cirrhosis | 48 months after the beginning of the project | The discriminating power of the HCC Test will be measured using the C-index |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3D morphology of extracellular vesicles | 48 months after the beginning of the project | size of microvesicles in nm |
| Quantification of Extracellular vesicles proteins | 48 months after the beginning of the project | Number of extracellular vesicles |
| number of patients with extreme values of extracellular vesicles in the general population | 48 months after the beginning of the project | Extracellular vesicles concentration per mL |
| Extracellular vesicles plasma concentrations in the general population | 48 months after the beginning of the project | Extracellular vesicles concentration per mL |
| Size of Extracellular vesicles proteins and the experimental repeatability | 48 months after the beginning of the project | size of extracellular vesicles in nm |
Countries
France
Contacts
Primary ContactPierre Emmanuel RAUTOU
Outcome results
None listed