NAFLD tissue project V1

  • Research type

    Research Study

  • Full title

    Analysis of patient-derived tissues to characterise the spectrum of NAFLD to establish mechanisms driving liver disease, enhance biomarker identification and drug discovery.

  • IRAS ID

    309924

  • Contact name

    Ryan Buchanan

  • Contact email

    ryan.buchanan@soton.ac.uk

  • Sponsor organisation

    University of Southampton

  • Duration of Study in the UK

    9 years, 11 months, 31 days

  • Research summary

    Background
    Non-alcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver diseases that ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) which may lead to fibrosis (tissue scarring) and result in liver cirrhosis. NAFLD dramatically increases the prevalence of hepatocellular carcinoma development. There is currently no cure for NAFLD, yet it is projected to become the leading cause of liver related morbidity and mortality within 20 years, and a leading indication for liver transplantation in the next few years.

    Objectives
    To understand the mechanisms driving NAFLD progression toward end stage liver disease to identify potential prognostic and therapeutic strategies.

    1. Generate in vitro models to replicate the spectrum of progressive liver diseases including NASH, NAFLD and liver cancer by using organoid cultures.
    2. Phenotypically characterise patients along the spectrum of disease through advanced imaging and molecular profiling (transcriptomic, metabolomic and lipidomic).
    3. Determine the role of subcutaneous and visceral adipose tissue in driving ectopic fat accumulation and/or liver disease progression.
    4. Investigate how immunosurveillance of the liver and adipose impacts on disease progression.

    How will it be done?
    We will screen patients undergoing bariatric surgery and hepatobiliary surgery to determine the clinical status of their liver on the NAFLD spectrum. We will identify patients representing different stages of NAFLD and ask if they would be willing to donate some liver tissue to be collected during their surgery procedure. The sampled liver, adipose, skin biopsies and peripheral blood will be collected by the surgical team and passed to the researchers for analysis. The results have the potential to enhance biomarker identification and drug discovery.

    Sample size: Up to 100 patients will enter the study of which approximately 40 will go on to be sampled.
    Inclusion Criteria: Men and Women, with the capacity to consent, age of 18 or over.

  • REC name

    London - Queen Square Research Ethics Committee

  • REC reference

    24/LO/0313

  • Date of REC Opinion

    6 Jun 2024

  • REC opinion

    Further Information Favourable Opinion