Liver disease is the 11th commonest cause of death globally and the leading cause of premature deaths in the UK. The main aetiologies are steatotic liver disease (alcohol related and metabolic dysfunction) and viral hepatitis. Autoimmune liver disease is also important. Epidemiological studies have shown that genetic, lifestyle and environmental risk factors determine predisposition, development, progression and outcomes from liver disease. Curative treatment in liver disease is lacking, except in the case of direct-acting antivirals for hepatitis C. Despite advances in understanding, the risk mechanisms, pathophysiology and their implications remain incompletely characterised. Building on this knowledge gap creates the potential to discover new therapeutic targets, early identification of at-risk individuals, novel biomarkers and inform clinical management in liver disease.
The objectives of this proposed study are to:
1. Characterise liver disease risk factors (genetic, environmental and lifestyle).
2. Identify biological mechanisms underpinning chronic liver disease including genetic pleiotropy.
3. Explore implications of identified risk factors and biology on outcomes and treatment response.
4. Understand how liver disease can impact on metabolism of concomitant drugs (the liver is the main site of drug metabolism) and therefore on patient outcomes.