DeLIVER Hypotheses and Goals
a) HCC is primarily driven by liver microenvironmental (immune, metabolic, stromal) processes, with inflammatory signals establishing epigenetic programmes that contribute to malignant transformation. Understanding the pathway to malignant transformation will drive new HCC-EDx (and therapeutic) strategies.
b) Combination state-of-the-art molecular and imaging strategies can be used for HCC-EDx in at-risk patient populations, increasing the opportunity to deliver curative therapies.
These hypotheses provide the rationale for the methodology and selection of technologies in the proposed integrated HCC-EDx research programme DeLIVER.
a) Define the pre-cancerous microenvironmental liver landscape that drives malignant transformation through deep-phenotyping of the pre-cancerous liver.
b) Assess technologies that may “sample” the pre-cancerous liver environment non-invasively, including the simultaneous detection of epigenetic/genetic information in blood (TAPS)
c) Perform an integrative analysis of multi-parametric datasets (including quantitative mpMRI, TAPS, metabolomic and protein(omic) biomarkers) since it is unlikely that a single parameter will accurately predict/detect early HCC.
d) Develop HCC-EDx cohorts by leveraging a unique, genetically characterised cohort of HCV-infected patients with cirrhosis to include additional disease aetiologies and establishing a cohort of patients with small HCC so that EDx technologies can be rapidly evaluated before testing prospectively.
e) Exploit our internationally recognised expertise integrating germline host and viral genomic polymorphisms that may predispose to malignant transformation.
The research questions will be addressed through six work packages within the DeLIVER programme.