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.

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)

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