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

Recruiting

• Conditions: Hepatitis C Virus Infection

• Registration Number: NCT06718530
• Lead Sponsor: Centro di Riferimento Oncologico - Aviano

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-13
• Status Verified: 2024-12
• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-02
• Last Update Submitted: 2024-12-02
• Study First Posted: 2024-12-05
• Last Update Posted: 2024-12-05
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Define a relationship between IgG levels toward HCV-specific peptides and viral load/development clinical after 2 years of follow-up	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
Define a relationship between IgG levels toward HCV-specific peptides and HCV genotype	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)
Characterization of Interferon Lambda 4 (INFL4) and Human Leukocyte antigene (HLA-E) variants within patient with or without HCV related hepatocarcinoma (HCC)	up to 2 years	Frequencies of genetic variants within patient with or without HCV related hepatocarcinoma (HCC) will be reported
Characterization of INFL4 and HLA-E variants within patient with or without HCV related chronic hepatitis	up to 2 years	Frequencies of genetic variants within patient with or without HCV related chronic hepatitis will be reported
Define the mRNA pathways activated in the subjects with expression of INFL4 and of HLA-E	up to 2 years	Data will be illustrated with volcano plot and heat map

Trial Locations

Locations (4)

Centro di Riferimento Oncologico (CRO) di aviano-IRCCS; 🇮🇹 Aviano, Pordenone, Italy

AORN S.Anna e S. Sebastiano, Via F. Palasciano; 🇮🇹 Caserta, Italy

Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale"; 🇮🇹 Napoli, Italy

Dip. Univ. Clin. di Scienze mediche, chirurgiche e della salute Università di Trieste; 🇮🇹 Trieste, Italy