Cirrhosis, Epigenomics, Hepatocellular Carcinoma (HCC), Risk Prediction for Liver Cancer
Conditions
Keywords
Hepatocellular Carcinoma, Cirrhosis, mSEPT9 Biomarker, Epigenetics, Risk Prediction, Liver Cancer Surveillance, Prospective Cohort Study, Non-Invasive Biomarkers, Personalized Medicine, Epigenomics, Risk Stratification
Brief summary
This study aims to evaluate the role of the circulating epigenetic biomarker mSEPT9 in predicting the risk of hepatocellular carcinoma (HCC) in patients with cirrhosis. HCC is a primary liver cancer that frequently develops in individuals with cirrhosis, and early detection is critical for improving outcomes. This research involves 400 patients with cirrhosis who will be followed every six months for up to 60 months. During these visits, blood samples will be collected to analyze mSEPT9 levels. By identifying changes in this biomarker, the study seeks to improve early diagnosis and personalize surveillance strategies, potentially enhancing patient survival and quality of life.
Detailed description
This study is a prospective, multicenter cohort trial designed to assess the prognostic utility of the circulating epigenetic biomarker mSEPT9 in predicting the development of hepatocellular carcinoma (HCC) among patients with cirrhosis. The trial involves 400 participants who are confirmed to have cirrhosis and no evidence of HCC at baseline. The study's primary focus is to evaluate the association between a "switch" in the mSEPT9 test-from a triple-negative status (no methylation detected across triplicate assays) to at least one positive triplicate-and the subsequent occurrence of HCC. Secondary objectives include assessing this association across different etiologies of cirrhosis (e.g., viral hepatitis, alcohol-related liver disease, nonalcoholic steatohepatitis) and its correlation with HCC-related mortality. Participants will undergo standardized clinical, biological, and imaging assessments every six months over a follow-up period of 60 months, as per international guidelines for cirrhosis management. In addition to routine care, blood samples will be collected at each visit for mSEPT9 testing. These samples will be processed, stored at -80°C, and analyzed in batches to assess mSEPT9 levels. The findings from this study are expected to address the unmet need for reliable, non-invasive biomarkers for HCC risk prediction, potentially leading to personalized surveillance strategies and earlier intervention for patients with cirrhosis. Data will be managed using an electronic case report form (eCRF) to ensure secure, standardized documentation across all participating centers. Results from mSEPT9 testing will not influence clinical management during the study period but will be analyzed to determine their predictive value for HCC development and prognosis.
Interventions
DIAGNOSTIC_TESTCirculating mSEPT9 Biomarker Testing
This intervention involves the analysis of the circulating epigenetic biomarker mSEPT9 through plasma samples collected from patients with cirrhosis. The mSEPT9 test evaluates the methylation status of the SEPT9 gene promoter using a triplicate assay. A "switch" in the test status, defined as a transition from triple-negative (no methylation detected in any triplicate) to at least one positive triplicate, is being investigated as a prognostic marker for the development of hepatocellular carcinoma (HCC). The mSEPT9 test is conducted on plasma samples collected during routine blood draws at each of the 11 scheduled study visits. Samples are processed and analyzed in batches using specialized high-throughput equipment provided by Epigenomics/New Day Diagnostics. Results of the mSEPT9 test are not shared with clinicians during the study period to avoid influencing patient management, ensuring the test is purely investigational in this context.
Sponsors
Central Hospital, Nancy, France
New Day Diagnostics
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 18 years or older. * Patients diagnosed with cirrhosis confirmed by clinical, biochemical, radiological, or histological criteria. * Cirrhosis attributable to one or more of the following etiologies: alcohol, hepatitis C (HCV), hepatitis B (HBV), nonalcoholic steatohepatitis (NASH), hemochromatosis, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, or cryptogenic causes. * Patients actively followed in one of the participating study centers. * Patients affiliated with a social security program or equivalent. * Patients with a body weight greater than 45 kg. * Patients who have been fully informed about the study procedures and have provided oral informed consent.
Exclusion criteria
* History of hepatocellular carcinoma (HCC). * History of any other primary or secondary malignant liver tumor. * Diagnosis of malignancy or hematologic disorders within the past 5 years (without time limitation for hematologic malignancies). * Patients currently undergoing hemodialysis. * Pregnant or breastfeeding women. * Individuals under legal protection (e.g., guardianship, curatorship) or unable to provide consent. * Minors or individuals younger than 18 years. * Individuals deprived of liberty by judicial or administrative order. * Patients with psychiatric conditions receiving care under legal constraints (e.g., articles L.3212-1 and L.3213-1). * Patients unable to comply with the study protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Association Between mSEPT9 Test Switch and Hepatocellular Carcinoma (HCC) Development | Annually for up to 60 months or until the occurrence of HCC, whichever occurs first. | Evaluate the relationship between a 'switch' in the mSEPT9 test result-defined as a transition from triple-negative (no methylation detected across all triplicates) to at least one positive triplicate-and the occurrence of hepatocellular carcinoma (HCC), as diagnosed using international criteria established by the AASLD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association Between mSEPT9 Test Switch and HCC Development by Cirrhosis Etiology | Annually for up to 60 months or until the occurrence of HCC, whichever occurs first. | Assess the association between a 'switch' in mSEPT9 test results and the development of hepatocellular carcinoma (HCC), as diagnosed using international criteria (AASLD), across subgroups categorized by cirrhosis etiology, including alcohol use, hepatitis B (HBV), hepatitis C (HCV), and nonalcoholic steatohepatitis (NASH). A 'switch' in the mSEPT9 test result is defined as a transition from triple-negative (no methylation detected across all triplicates) to at least one positive triplicate. |
| Association Between mSEPT9 Test Results and HCC-Related Mortality | Annually for up to 60 months or until HCC-specific death occurs. | HCC-specific mortality, defined as death attributable to hepatocellular carcinoma based on international classification of diseases (ICD) coding and/or clinical determination, stratified by positive or negative mSEPT9 test results (performed in triplicate). |
| Establishment of a Biobank for Genomic and Epigenomic Analysis | For each participant, samples will be collected at enrollment (baseline) and during follow-up visits every 6 months for up to 60 months. | Number of Plasma and DNA Samples Collected and Stored for Genomic and Epigenomic Analysis, Including Data on Sample Quality, Quantity. |
Countries
France
Contacts
CONTACTProf. Abderrahim OUSSALAH, MD, PhD
STUDY_DIRECTORMr. Franck Schreiner
Regional and University Hospital Center of Nancy
Outcome results
None listed