Clinical trial NCT06718530: Characterization of Immune Genotypes and Antibody Profiles to Foster the discoVERY of diagnosticbioMARKERS of Liver Cancer Development
Official title: Characterization of Immune Genotypes and Antibody Profiles to Foster the discoVERY of diagnosticbioMARKERS of Liver Cancer Development
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatitis C Virus Infection
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2024-12-05
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Difference in antibody profile between subjects with and without chronic HCV infection
timeFrame: up to 2 years
measure: Difference in antibody profile between subjects with chronic HCV infection receiving or not receiving DAA therapy
timeFrame: up to 2 years
Secondary outcomes:
measure: Define a relationship between IgG levels toward HCV-specific peptides and viral load/development clinical after 2 years of follow-up
timeFrame: up to 2 years
measure: Define a relationship between IgG levels toward HCV-specific peptides and HCV genotype
timeFrame: up to 2 years
measure: Characterization of Interferon Lambda 4 (INFL4) and Human Leukocyte antigene (HLA-E) variants within patient with or without HCV related hepatocarcinoma (HCC)
timeFrame: up to 2 years
measure: Characterization of INFL4 and HLA-E variants within patient with or without HCV related chronic hepatitis
timeFrame: up to 2 years
measure: Define the mRNA pathways activated in the subjects with expression of INFL4 and of HLA-E
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico (CRO) di aviano-IRCCS
state: Pordenone
city: Caserta
country: Italy
facility: AORN S.Anna e S. Sebastiano, Via F. Palasciano
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale"
city: Trieste
country: Italy
facility: Dip. Univ. Clin. di Scienze mediche, chirurgiche e della salute Università di Trieste
Study officials:
affiliation: Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS
name: Valli De Re, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS
name: Renato Cannizzaro, MD
role: PRINCIPAL_INVESTIGATOR
References: