mSEPT9 Biomarker for Predicting Hepatocellular Carcinoma Occurrence in Patients With Cirrhosis

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.

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.