Diagnostic challenges in hepatology practice



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.
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 result: 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.
  • Expected result: 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.

Partici​pants
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 (Hans Van Vlierberghe, Xavier 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, three VIB core facilities are involved: Nucleomics, Proteomics and Metabolomics. The nucleomics core is involved on a fee-for-service basis only, whereas the Proteomics and Metabolomics core are also involved as R&D partners, as they bring in newly developed methodologies.


VIB
  • ​​Nico Callewaert (promotor-spokesperson)
  • Lennart Martens 
  • Kris Gevaert
  • Francis Impens
  • Bart Ghesquière
  • Leander Meuris
UGent/ UZ Gent 
  • Hans Van Vliergberghe
  • Xavier Verhelst
  • Jo Vandesompele
UZ Leuven
  • David Cassiman
UZA
  • Sven Francque


-> Go back to the overview page of ​ 'VIB Grand Challenges Program'​​

 

 
 

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Nico Callewaert
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