Characterization of Immune Genotypes and Antibody Profiles to Foster the discoVERY of diagnosticbioMARKERS of Liver Cancer Development (VERYMARKERS)

December 2, 2024 updated by: Centro di Riferimento Oncologico - Aviano

Hepatitis C virus (HCV), which infects more than 185 million people, is a major risk factor. Direct-acting antiviral (DAA) therapy has significantly improved the eradication of the virus, but has not completely eliminated the risk of HCC, so careful surveillance is necessary. The genetic diversity of the natural killer receptor, histocompatibility antigens (HLA) and interferon lambda 4 (INFL4) activity, among other factors, have been found to be crucial in directing disease progression. Importantly, these markers are detectable years before the diagnosis of HCC. In addition, polymorphic variants attributable to the expression of genes involved in innate-type immune response, such as IFNL4 and HLA-E, have been shown to be predictive for the development of HCC and have not yet been extensively studied. The aim of the study is to evaluate novel circulating biomarkers, including the presence of antibodies to specific HCV proteome peptides, IFNL4 expression, and the interaction of specific HLA receptors/ligands in a large cohort of HCV-positive subjects in order to create a screening strategy for the early diagnosis of HCV-associated HCC.

Part of the study will be devoted to describing the immune microenvironment associated with the expression of IFNL4 and HLAE, evaluating them as potential prognostic indicators for HCC in HCV-infected subjects undergoing surgery for HCC, as well as in those with advanced/metastatic HCC.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

1000

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

  • Name: Valli De Re, PhD
  • Phone Number: +39 0434 659672
  • Email: vdere@cro.it

Study Locations

  • Italy
      • Caserta, Italy
      • Napoli, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale"
        • Contact:
      • Trieste, Italy
        • Recruiting
        • Dip. Univ. Clin. di Scienze mediche, chirurgiche e della salute Università di Trieste
        • Contact:
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Recruiting
        • Centro di Riferimento Oncologico (CRO) di aviano-IRCCS
        • Contact:
          • Valli De Re, PhD
          • Phone Number: +39 0434 659672
          • Email: vdere@cro.it

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

Non-Probability Sample

Study Population

The study population consists of patients with varying degrees of liver damage, diagnosed with of HCC or HCV-positive with diagnosed cirrhosis, fibrosis or long-term HCV infection

Description

Inclusion Criteria:

  • Patients aged ≥18 years with the presence of chronic infection, fibrosis, cirrhosis or HCV- associated HCC
  • Patients able to understand and willing to sign the of informed consent
  • Patients to answer the questions in the questionnaire of enrollment

Exclusion Criteria:

  • Treatment for other oncological diseases
  • Immunodepression congenital or acquired (HIV, organ transplantation, pharmacological)

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in antibody profile between subjects with and without chronic HCV infection
Time Frame: up to 2 years
Mean or median difference between the groups, as appropriate, will be calculated
up to 2 years
Difference in antibody profile between subjects with chronic HCV infection receiving or not receiving DAA therapy
Time Frame: up to 2 years
Mean or median difference between the groups, as appropriate, will be calculated
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Define a relationship between IgG levels toward HCV-specific peptides and viral load/development clinical after 2 years of follow-up
Time Frame: up to 2 years
Correlation coefficient between the highest IgG levels towards at least one specific HCV peptide and high viral load will be calculated
up to 2 years
Define a relationship between IgG levels toward HCV-specific peptides and HCV genotype
Time Frame: up to 2 years
Relation will be analyzed with logistic regression analysis and represented with Odds Ratio (OR) and relative 95% Confidence Interval (95% CI)
up to 2 years
Characterization of Interferon Lambda 4 (INFL4) and Human Leukocyte antigene (HLA-E) variants within patient with or without HCV related hepatocarcinoma (HCC)
Time Frame: up to 2 years
Frequencies of genetic variants within patient with or without HCV related hepatocarcinoma (HCC) will be reported
up to 2 years
Characterization of INFL4 and HLA-E variants within patient with or without HCV related chronic hepatitis
Time Frame: up to 2 years
Frequencies of genetic variants within patient with or without HCV related chronic hepatitis will be reported
up to 2 years
Define the mRNA pathways activated in the subjects with expression of INFL4 and of HLA-E
Time Frame: up to 2 years
Data will be illustrated with volcano plot and heat map
up to 2 years

Collaborators and Investigators

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

Sponsor

Centro di Riferimento Oncologico - Aviano

Investigators

  • Principal Investigator: Valli De Re, PhD, Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS
  • Principal Investigator: Renato Cannizzaro, MD, Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS

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)

May 13, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

December 2, 2024

First Submitted That Met QC Criteria

December 2, 2024

First Posted (Estimated)

December 5, 2024

Study Record Updates

Last Update Posted (Estimated)

December 5, 2024

Last Update Submitted That Met QC Criteria

December 2, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRO-2024-42

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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