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The DeLIVER hypotheses are:

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.

The DeLIVER goals are:

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. 

 

 Liver Diagram

Research questions will be addressed through six work packages of the DeLIVER programme.