Joint Transnational Call 2023 (JTC2023)
RiTA: PortoSinusoidal Vascular Disease: Risk stratification & Therapeutic Approaches
Porto-sinusoidal vascular disorder involves a group of diseases that commonly damage the intrahepatic vessels at the level of the portal venules and/or the sinusoids, in the absence of cirrhosis, and share a similar clinical phenotype (non-cirrhotic PH), suggesting common underlying biological mechanisms. PSVD primarily affects young individuals, with an average age of presentation at 40 years, and has a prevalence of 1.8 cases per 100,000 people, with a male-to-female ratio of 2:1. Currently, there are no treatments available to modify the natural course of the disease or biomarkers that can predict patient prognosis. Management is limited to symptomatic treatment of PH, which is the main contributor to mortality. The overall 10-year survival rate without requiring a liver transplant ranges from 40% to 82%, with a 5% liver transplant rate at 5 years. Lack of suitable preclinical models and limited understanding of the disease’s pathophysiology hinder the development of new therapies.
The primary goal of the RiTA project is to investigate the natural history and progression of PSVD in order to develop tools that can predict patient prognosis and identify new therapeutic targets. This will be accomplished through four specific aims: 1) Characterizing the heterogeneity of the disease and identifying prognostic scores based on clinical data. 2) Identifying patient-reported outcomes (PROs) and quality of life (QoL) measures that can serve as relevant endpoints. 3) Developing mechanistic biomarkers with prognostic value. 4) Identifying actionable therapeutic targets.
Our strategy to achieve these objectives relies on a scientifically strong and multidisciplinary consortium including patient associations. This collaboration will allow for the inclusion of a large number of patients and the pooling of diverse expertise, enabling groundbreaking research using state-of-the-art technology.
The expected results of the RiTA project will have a significant impact on patient management by: 1) Enabling the identification of high-risk patients prone to decompensation or mortality through prognostic scores or biomarkers. 2) Increasing awareness of this often-overlooked disorder, leading to more timely and accurate diagnoses and reducing instances of misdiagnosis. 3) Quantifying the impact of PSVD on quality of life and identifying relevant PROs that can potentially serve as surrogate endpoints in future studies. 4) Initiating the discovery process for new treatments. 5) Empowering patients through active involvement and participation in their own healthcare decisions.
Overall, the RiTA project aims to advance our understanding of PSVD, facilitate the development of personalized management strategies, and improve the lives of patients.
- Hernández-Gea (Coordinator)[SPAIN]
- Rautou [FRANCE]
- Zanetto [ITALY]
- Dumas [FRANCE]
- Heikenwaelder [GERMANY]
- Itzkovitz [ISRAEL]