Liver Physiology & Metabolism Research Group
Who are we?
- Guru Aithal is Professor of Hepatology in Translational Medical Sciences and lead for the Nottingham Digestive Diseases Centre community in the School of Medicine.
- Jane Grove is Associate Professor in Translational Medical Sciences.
- Stuart Astbury is Senior Research Fellow in Translational Medical Sciences.
- Dr Saikat Mandal is a Clinical Research Fellow in Translational Medical Sciences.
- Dr Jessica Wong is a Clinical Research Fellow in Translational Medical Sciences.
We are part of the NIHR Nottingham Biomedical Research Centre. We work with the TransBioLine Consortium Research Partnership which is funded through the Innovative Health Initiative (IHI) and includes industry, academic and small/medium enterprises. The TransBioLine project aims to develop novel safety biomarkers that will reliably indicate injury of the liver, kidneys, pancreas, blood vessels, and central nervous system for drug development purposes.
We also contribute to UK and European collaborative projects DEMISTIFI, LITMUS and Pro-Euro DILI Network.
Liver Disease
Liver disease is now the third leading cause of premature death.
The liver disorders we investigate through our research portfolio include:
- Drug-induced liver injury (DILI): DILI is a rare, yet serious adverse reaction to medications and our research has developed well characterised cohorts of patient cases and healthy controls to investigate the genetic, epigenetics and environmental factors involved. We have led an international collaboration performing genome wide association studies (GWAS), discovering single nucleotide polymorphisms (SNPs) underlying susceptibility to drug induced liver injury (DILI). Our work also aims to discover tests that can be used for diagnosis of DILI.
- Metabolic-dysfunction associated steatotic liver disease (MASLD): Steatotic liver diseases all involve having excess fat in the liver. This is thought to occur in around 30-50% of the population but often gives no symptoms. Our research aims to compare the features of people with fatty liver to those with MASLD and to people with no disease. Our goal is to develop new non-invasive tests to specifically diagnose fatty liver disease, MASLD and predict disease progression as an alternative to liver biopsy.
- Alcoholic liver disease (ALD): ALD is a general term for liver disease caused by harmful levels of alcohol consumption, it includes fatty liver (steatosis), alcohol-related steatohepatitis (ASH) with or without associated fibrosis and/or cirrhosis.
- Hepatocellular Carcinoma (Liver Cancer): Can arise in patients where their liver disease progresses and scarring (fibrosis) occurs. We aim to idenitify blood tests that can predict when cancer could develop and develop tests to monitor liver disease.
- Cholangiocarcinoma (bile duct cancer) (CCA): Affects 3000 people in the UK each year, with dismal prognosis: only 13% of patients survive 3 years. CCA arises in the bile duct, which is a narrow tube. As the cancer grows inside the bile duct, it is further narrowed, and routine scans cannot confirm if the narrowing is due to inflammation or the cancer. Diagnosis relies on the microscopy of samples taken from the narrowed area, but, when narrowed or blocked, it is even harder to obtain samples.
We have a number of research projects which are currently recruiting participants:
Drug-Induced Liver Injury studies
Pro-Euro DILI Registry (DILI):
This is an international project and bioresource to enable research into the causes and characteristics of drug-induced liver injury (DILI) so that new, non-invasive diagnostic tests can be developed. The goal is to predict and prevent drug-induced liver injury (DILI) so patients can be safely treated with medications they need.
Checkpoint Inhibitor-Induced Liver Injury Study (ChILI):
Multi-centre prospective observational study to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it. More information about this study can be found on the clinical trials.gov website.
Liver Disease Itching Study:
This is a multi-centre prospective observational study to investigate why some patients who experience liver injury caused unexpectedly by drugs/supplements suffer from itching symptoms, and how it affects their quality of life. We aim to find out if there are certain rare genetic variations linked to this and what factors affect the severity of itching.This will be part of a student PhD project.
Methotrexate Study:
This study investigates the effectiveness of certain non-invasive tests in the detection of liver scarring in patients with rheumatoid arthritis or psoriasis who are currently on methotrexate.
Chronic Liver Disease Studies
NASH Genotype
This study evaluates possible genetic reasons for the development of non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) and the progression of fatty liver.
Fighting Fatty Liver in India
The Global Challenge Research Fund (GCRF) has catalysed our ‘Fighting Fatty Liver’ programme in collaboration with the Population Health and Research Unit and Holistic Health and Research Institue, Trivandrum, Kerela, India and Holistic Health Research Institue Our ambition is to bring about substantial and sustainable change in the burden of fatty liver and its consequences through the development and implementation of culturally sensitive community based interventions. More information about this study can be found on the Clinical Trials.gov website
The Nottingham Digestive Disease Centre Biomedical Research Tissue Bank
The Nottingham Digestive Diseases Centre Biomedical Research Unit Tissue Bank
The NDDC BRU Research Tissue Bank is a local collection of biological samples from patients and research participants to facilitate new research projects investigating digestive health. The aim is to provide high quality biological samples to researchers worldwide for projects to improve the health and care of patients in the future.
Cholangiocarcinoma Study:
Our vision is to bring expertise from multiple disciplines together to develop a new technology with enhanced dexterity to navigate the biliary stricture, develop capabilities for tissue molecular mapping, and create capability to deliver treatment with greater precision. This is expected to then lead to improved survival and quality of life outcomes for patients with CCA.