Improving liver disease diagnosis

Background

Chronic liver disease is a major cause of morbidity and mortality worldwide, with increasing prevalence. In terms of total years of life lost, it is now the 13-th most burdensome disease overall and the 5-th leading cause of death in the young adult age group of 25-50 years. In Europe, liver disease causes 2% of all deaths. The main etiologies are chronic HBV and HCV infection, alcohol abuse and, rapidly increasingly, nonalcoholic fatty liver disease (NAFLD) that is associated with insulin resistance and obesity. All of these lead to hepatocyte cell death and chronic liver inflammation, often triggering liver fibrosis and progressive loss of functional liver architecture. In the cirrhosis stage of the disease, nodular hepatocyte proliferation occurs in this inflammatory environment, increasing the risk of hepatocellular carcinoma up to 40-fold. Furthermore, progressive cirrhosis leads to hepatic decompensation symptoms (portal hypertension-related ascites, varices and hepatorenal syndrome, as well as complications relating to liver dysfunction, such as jaundice, coagulopathy and encephalopathy), requiring liver transplantation. Preventive approaches to date are insufficiently effective.

Goals

Without improved diagnostics, the cost-effectiveness of intervention using existing and emerging pharmacological and surgical treatments will remain suboptimal.
For these reasons, this hepatology biomarker VIB-GCP project is entirely driven by the following main diagnostic challenges:

  • Diagnostic challenge in hepatology 1: biomarker-based detection of NASH and the activity of the pathogenic processes in NASH in patients with steatosis, to guide treatment decisions and monitor the outcome of treatment.

  • Diagnostic challenge in hepatology 2: increasing the proportion of hepatocellular carcinomas that are detected at an early stage, to enable curative treatment in a higher proportion of patients.

  • Diagnostic challenge in hepatology 3: avoiding transplantation of livers that will lead to catastrophic Primary Non-Function (PNF).

This VIB-GCP collaboration guarantees the further translation of established glycomics-based candidate biomarkers for the three diagnostic challenges listed above. These can go straight into validation studies and alphasite usage along current clinical practice to start yielding benefit for the hepatology patients in our University Hospitals. On top of that, the core discovery technologies proposed are all ready to go to clinical validation or exploration after these years of prior technology development.
Over the course of this 3-year Grand Challenge program, the following results are expected:

  • Expected results:

    • biomarkers with full clinical utility validation at the end of the project. Clinical investigational utilization in 3 key tertiary care key opinion leader centers in Flanders.

    • biomarkers with solid clinical proof of concept, some of which fully prospectively validated and some of which the prospective validation will be well under way at the end of the 3-year project. Significant IP on novel biomarkers.

Facts & Figures

Start date:
07/11/2018
End date:
06/11/2021
Call:
Call 1
Funding:
2.5M€

Thematic area

Innovative biomarkers

Precision medicine will be improved by translating innovative molecular diagnostic paradigms into clinical practice.

Promotor

Partners

The VIB Center for Medical Biotechnology (Director: Nico Callewaert) will coordinate the project and serve as the home base for the team that develops and performs the wet lab analytics as well as the data warehousing and data analysis. 

This VIB Center has joined forces with top expert hepatologists from the leading 3 university hospital hepatology and transplantation centers in Flanders.

 

VIB-UGent

Nico Callewaert • Lennart Martens • Kris Gevaert • Francis Impens • Leander Meuris

VIB-KU Leuven

Bart Ghesquière

UGent-UZ Gent

Jo Vandesompele​ • Hans Van Vliergberghe • Xavier Verhelst

KU Leuven-UZ Leuven

David Cassiman

UZA

Sven Francque

Contribution to the project

The VIB Center for Medical Biotechnology (Director: Nico Callewaert) coordinates the project and serves as the home base for the team that develops and performs the wet lab analytics as well as the data warehousing and data analysis.  This VIB Center has joined forces with top expert hepatologists from the leading 3 university hospital hepatology and transplantation centers in Flanders (Hans Van Vlierberghe, Xavier Verhelst, Sven Francque, David Cassiman).  Finally, four VIB core facilities are involved as R&D partner or service provider.

Expected impact

This project will draw attention to chronic liver diseases as a prevalent and ‘invisible’ scourge of 21st century healthcare with a huge impact on patient lives, healthcare systems, and clinical developments. As part of this project, multiple stakeholders will be involved in empowering patients to make the case for prioritization of research into chronic liver failure and potential new diagnostics and treatment options.

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Leander Meuris (VIB-UGent Center for Medical Biotechnology) says:

“As involved researcher, this project allows me to close the gap between research and healthcare, something I consider to be very important in pursuing research beneficial to patients.”

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Contact

Sofie Bekaert, Manager Translational Program