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

Обзор

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.

Первичные конечные точки

• Difference in antibody profile between subjects with and without chronic HCV infection [Срок оценки: up to 2 years]
• Difference in antibody profile between subjects with chronic HCV infection receiving or not receiving DAA therapy [Срок оценки: up to 2 years]

Вторичные конечные точки (5)

• Define a relationship between IgG levels toward HCV-specific peptides and viral load/development clinical after 2 years of follow-up [Срок оценки: up to 2 years]
• Define a relationship between IgG levels toward HCV-specific peptides and HCV genotype [Срок оценки: 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) [Срок оценки: up to 2 years]
• Characterization of INFL4 and HLA-E variants within patient with or without HCV related chronic hepatitis [Срок оценки: up to 2 years]
• Define the mRNA pathways activated in the subjects with expression of INFL4 and of HLA-E [Срок оценки: up to 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 4 центра

• Centro di Riferimento Oncologico (CRO) di aviano-IRCCS — Aviano
• AORN S.Anna e S. Sebastiano, Via F. Palasciano — Caserta
• Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale" — Naples
• Dip. Univ. Clin. di Scienze mediche, chirurgiche e della salute Università di Trieste — Trieste

Идентификаторы

NCT: NCT06718530 · CRO-2024-42

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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