Developing Diagnostic and Prognostic Tests in Chronic Liver Disease
Chronic liver disease displays clinical symptoms at the very late stages (50% of new diagnoses of severe disease present for the first time as an emergency admission). The current tests to detect early liver disease lack accuracy, are invasive, expensive and inconvenient to patients. Moreover, they have limited utility to assess drug efficacy and are a critical barrier to drug development (i.e. anti-fibrotic medication) in this area.
We have a major focus on developing and validating tests of diagnosis and prognosis in chronic liver injury with a view to changing clinical practice. To fulfill this aim we have three broad strategies:
- The creation of a “deep” phenotype of patients who have been stratified for chronic liver disease across a spectrum of conditions (e.g. NAFLD, HCV and Alcohol) and severity of disease (e.g. East Midlands community cohort of liver disease, Nottingham NAFLD cohort, Nottingham cirrhosis cohort and national HCV cirrhosis study)
- Collaboration with basic scientists within Nottingham and externally to develop early biomarkers of liver injury (e.g. Quantitative tools of MR Imaging, markers of collagen turnover, serum biomarkers of apoptosis and necro-inflammation, etc)
- Working with partner organisations including PPI, Industry, Academic Health Science Networks and NIHR Diagnostic Evidence Co-operatives to a) address the priority areas and then b) deliver a solution.
Our work has produced:
- High impact scientific papers (over 50 diagnostic/prognostic publications in last 5 years)
- Greater than 2 million pounds of grant income in last 5 years (including NIHR, MRC, Pfizer, and AHSN funding).
- NHS innovations challenge award winners in diagnostics 2013 http://www.nhschallengeprizes.org/winners/neil-guha-guruprasad-aithal
- High profile public engagement events including the Royal Society Summer ScienceExhibition in 2013
- Short listed for Gastroenterology Team of the year by the BMJ in 2015
We have research progammes which address the spectrum of disease severity (from risk factor to decompensation – see figure 1) and also the three major causes of liver disease in the UK (Alcohol, NAFLD and viral hepatitis). Examples of our funded work streams in diagnostic and prognostic studies include: Compensated Cirrhosis study in Nottingham (3CN) – PI Neil Guha. NIHR funded. MRQuee – Quantitative MRI for assessing portal hypertension- PI Guru Aithal. NIHR funded Biomarkers of early injury in NAFLD- PI Guru Aithal. NIHR funded. Early detection of liver disease in the community. PIs- Neil Guha and Guru Aithal. AHSN funded. Prognostic markers of HCV cirrhosis. PIs- Neil Guha and Will Irving. MRC funded. Dynamic Tests of chronic liver injury utilising MRI. PIs- Neil Guha, Sue Francis and Guru Aithal. MRC Tissue biomarkers of liver fibrosis . PIs – Neil Guha and Will Irving. Pfizer and Conatus funded
Potential for collaborative projects:
We would be interested in working with industry partners who either have a diagnostic test or device that requires clinical validation (early phase clinical trials are particularly welcome). We also have a track record of working with companies to support the development of diagnostics to aid their drug discovery programme.
Key team members (PIs):
Professor Guru Aithal
Dr Neil Guha
Dr Jane Grove
Professor Will Irving
Professor Penny Gowland
Dr Luca Marciani
Dr Sue Francis
Tel: +44 (0) 115 9709966