Investigating immunometabolism in advanced liver disease

• Research type

  Research Study

• Full title

  Investigating changes in immunometabolism underlying immune dysfunction in patients with advanced liver disease

• IRAS ID

  264150

• Contact name

  Alastair O'Brien

• Contact email

  a.o'brien@ucl.ac.uk

• Sponsor organisation

  UCL Joint Research Office

• Clinicaltrials.gov Identifier

  Z6364106/2019/06/44 , UCL Data Protection Office registration

• Duration of Study in the UK

  2 years, 0 months, 0 days

• Research summary

  Liver disease is rising with nearly 70,000 hospital admissions per year. The major causes are alcohol, obesity and chronic viral infections. Unfortunately, most patients develop symptoms at a very late stage, called acute decompensation (AD) or Acute-on-Chronic-Liver Failure (ACLF). These people are unwell and half will die within 2 years. They are 20 times more likely to develop an infection than those without liver disease due to a weakened immune system. The causes of this ‘cirrhosis-associated immune dysfunction’ (CAID) are unknown and no treatments exist to improve patients’ immune systems.
  Our research group is committed to a better understanding of the mechanisms underlying poor immune function in AD/ACLF to develop immune therapies. We hypothesise that CAID is driven by a reduced immune cell metabolism (processes that generate energy for the cell) and are investigating whether we can alter this to improve immune cell activity.
  The immune cells are all types of white blood cells, lymphocytes (T-cells, B-cells and NK cells), neutrophils, and monocytes/macrophages that work together to defend against infection and are dispersed throughout the body.
  Our pilot data has demonstrated that genes regulating metabolism and immune cell function differ substantially between healthy volunteers and AD/ACLF patients.
  We aim to take blood from healthy volunteers and patients with differing degrees of liver disease severity (stable and decompensated) from The Royal Free and University College Hospitals and will study differences in the levels and types of several “nutrient derived molecules” such as lipoproteins, fatty acids and aminoacids responsible for cell metabolic activity. In parallel, immune cells (monocytes and lymphocytes) will be isolated from the same individuals to examine the genetic control of cell function as well as live-cell metabolism of monocytes and lymphocytes. This work will identify potential targets for drug development to improve immune function in patients with advanced liver disease.

• REC name

  Social Care REC

• REC reference

  19/IEC08/0035

• Date of REC Opinion

  9 Sep 2019

• REC opinion

  Further Information Favourable Opinion