PRIN2022PNRR

Modelling Systemic and Lipoprotein Metabolism with “Multi-Omics” and “System Biology” approaches in HCV Patients with Residual Hepatic Steatosis after Viral Eradication (SysBioHCVSLD)

Funding Programme:  NATIONAL  RECOVERY  AND  RESILIENCE  PLAN  (NRRP)  –  MISSION  4 - COMPONENT 2 INVESTMENT 1.1 – “Fund for the National Research Program and for Projects of National Interest (NRP)” - PRIN 2022 PNRR

Project Code: P202222FCC

CUP: H53D23009960001

Principal Investigator: Prof. Michele Vacca

Institution: University of Bari Aldo Moro (UNIBA)

Department: Interdisciplinary Department of Medicine

Partner Institution: University of Salerno (UNISA) – Prof Mario Masarone

Background and Rationale.  Hepatitis C virus (HCV) infection has historically represented one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC) in Italy, particularly in southern regions. The introduction of direct-acting antivirals (DAAs) has revolutionised the natural history of HCV infection, enabling viral eradication in the vast majority of patients. However, an emerging clinical challenge is represented by the persistence or development of metabolic dysfunction and liver steatosis after viral clearance. A substantial proportion of patients remains at risk of disease progression despite successful antiviral therapy, highlighting the lack of reliable biomarkers to predict clinical outcomes and guide follow-up strategies. Understanding the mechanisms underlying this residual metabolic impairment and risk of steatosis progression is therefore essential to improve patient management and reduce long-term complications.

Project Objectives and Approach. This project aimed at providing a comprehensive characterization of the metabolic rewiring associated with post-HCV steatotic liver disease (SLD) through an integrated systems biology approach. The study combines detailed clinical phenotyping with advanced multi-omics analyses to investigate the interplay between lipid metabolism, genetic background, hormonal regulation, and disease progression. A well-characterized cohort of control subjects, MASLD patients, and individuals with post-HCV steatosis was established, enabling direct comparison between metabolic and post-viral forms of SLD. Biological samples were analysed using state-of-the-art technologies, including lipidomics (whole plasma and lipoprotein-resolved), untargeted metabolomics, APO peptidomics, and genetic profiling, complemented by hormonal and metabolic assessments. The integration of these datasets through advanced bioinformatic pipelines allows the identification of disease-specific metabolic signatures and provides insights into the molecular mechanisms driving persistent liver and systemic metabolic dysfunction after HCV eradication.

Impact and Future Perspectives: The project provides new insights into the pathophysiology of residual metabolic dysfunction and steatosis after HCV eradication, contributing to a better understanding of disease heterogeneity and progression. The identification of metabolic signatures associated with different steatotic phenotypes represents a key step toward the development of non-invasive biomarkers for patient stratification and risk assessment.  Overall, this project contributes to advancing research in hepatology and metabolic diseases, in line with the priorities of the PNRR and the European Horizon Programme, and supports the development of innovative strategies for the management of patients with liver disease.