mSEPT9 Biomarker for Predicting Hepatocellular Carcinoma Occurrence in Patients With Cirrhosis (SEPT9_SuRV)

June 8, 2026 updated by: Central Hospital, Nancy, France

Evaluation of the Circulating Epigenetic Biomarker mSEPT9 for Predicting the Occurrence of Hepatocellular Carcinoma in Patients With Cirrhosis: A Prospective Multicenter Trial (SEPT9_SuRV)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Vandœuvre-lès-Nancy, France, 54511

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The study population consists of 400 adult patients with confirmed cirrhosis who are actively followed in specialized hepatology centers across multiple institutions. Participants must not have hepatocellular carcinoma (HCC) at the time of enrollment and must meet specific inclusion criteria, including established cirrhosis etiology and eligibility for routine clinical follow-up. Patients with conditions that may interfere with the study objectives, such as a history of malignancy or ongoing hemodialysis, are excluded. This cohort represents a diverse range of cirrhosis etiologies, including viral hepatitis, alcohol-related liver disease, and nonalcoholic steatohepatitis (NASH), to ensure the generalizability of findings.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients With Cirrhosis Without Hepatocellular Carcinoma at Baseline
This cohort includes 400 patients with cirrhosis who do not have hepatocellular carcinoma (HCC) at the time of inclusion. Participants will undergo standard clinical, biological, and radiological evaluations every six months for a total follow-up duration of 60 months, in accordance with international guidelines for cirrhosis management. In addition to routine assessments, blood samples will be collected at each visit for the analysis of the circulating epigenetic biomarker mSEPT9. This biomarker will be tested to evaluate its utility in predicting the occurrence of HCC during the follow-up period. The results of the mSEPT9 test will not influence clinical management during the study.
Diagnostic test: Circulating 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.

Other Names:
  • Plasma mSEPT9 Testing
  • Epigenetic Biomarker Analysis
  • mSEPT9 Methylation Test

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association Between mSEPT9 Test Switch and Hepatocellular Carcinoma (HCC) Development
Time Frame: 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.
Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association Between mSEPT9 Test Switch and HCC Development by Cirrhosis Etiology
Time Frame: 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.
Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.
Association Between mSEPT9 Test Results and HCC-Related Mortality
Time Frame: 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).
Annually for up to 60 months or until HCC-specific death occurs.
Establishment of a Biobank for Genomic and Epigenomic Analysis
Time Frame: 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.
For each participant, samples will be collected at enrollment (baseline) and during follow-up visits every 6 months for up to 60 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Central Hospital, Nancy, France

Collaborators

New Day Diagnostics

Investigators

  • Study Director: Mr. Franck Schreiner, Regional and University Hospital Center of Nancy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 3, 2025

Primary Completion (Estimated)

June 3, 2033

Study Completion (Estimated)

June 3, 2033

Study Registration Dates

First Submitted

December 27, 2024

First Submitted That Met QC Criteria

January 14, 2025

First Posted (Actual)

January 16, 2025

Study Record Updates

Last Update Posted (Actual)

June 10, 2026

Last Update Submitted That Met QC Criteria

June 8, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-A01664-39

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The study will share individual participant data (IPD) related to anonymized clinical, biological, and imaging results, as well as the results of mSEPT9 biomarker analyses.

This includes:

  • Demographic data
  • Clinical characteristics, including cirrhosis etiology and disease severity (e.g., Child-Pugh score)
  • Results from routine imaging and biological assessments
  • mSEPT9 test results (e.g., triple-negative, positive status)
  • Outcome measures, such as the occurrence of hepatocellular carcinoma (HCC) and mortality

All shared data will be pseudo-anonymized to ensure participant confidentiality and will be accessible to researchers upon reasonable request, in accordance with regulatory and ethical guidelines.

IPD Sharing Access Criteria

The individual participant data (IPD) and supporting information will be available starting 12 months after the publication of the study results. IPD related to outcomes outside the primary and secondary objectives of the study may be discussed and shared on a case-by-case basis, contingent on appropriate approvals and compliance with applicable regulations.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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