PortoSinusoidal Vascular Disease: Risk stratification & Therapeutic Approaches

Porto-sinusoidal vascular disorder (PSVD) is a cluster of diseases that primarily affect the intrahepatic vasculature, resulting in portal hypertension (PH)and its associated life-threatening complications. The exact cause of this damage is still uncertain, and unfortunately, there are no targeted treatments available at present. Patients are only able to receive symptomatic care. Additionally, the absence of prognostic scores and biomarkers makes it difficult to identify individuals who are at a heightened risk of experiencing adverse outcomes. PSVD predominantly impacts young individuals and is frequently prone to misdiagnosis. As a consequence, it leads to disability, a significant reduction in quality of life, and places a considerable burden on the healthcare system. This burden is especially pronounced for individuals in their childbearing years and those economically active, resulting in substantial costs. Our overarching objective is to enhance our understanding of the natural history and progression of PSVD to define targets for future interventions through a comprehensive four-step approach:

1) Characterization of heterogeneity and identification of prognostic scores based on clinical data

2) Identification of patient-reported outcomes (PROs) and quality of life (QoL) measures that may become relevant endpoints

3) Development of mechanistic biomarkers with prognostic value

4) Identification of actionable therapeutic targets

To achieve these goals, our project brings together partners from diverse disciplines, including clinicians, experts in social sciences and humanities (SSH), basic researchers, and representatives of patients. This collaborative effort is supported by a well-balanced workplan involving participants from five EU countries. Work Package 1 (WP1) will focus on the development of risk stratification scores and prediction models for clinical events. WP2 will be dedicated to the definition of PROs. WP3 will delve into the examination of mechanistic biomarkers based on existing knowledge. WP4 will employ state-of-the-art approaches to deepen our understanding of the disease's underlying mechanisms and identify potential therapeutic targets. Lastly, WP5 will oversee the management of all work packages, ensuring effective coordination and progress throughout the project.

This project is an international collaborative effort, involving the following world-renowned Institutes: Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (Spain, coordinator), Assistance Publique – Hôpitaux de Paris and INSERM (France), University of Padova (Italy), German Cancer Research Center (Germany), Weizmann Institute of Science (Israel).