Case-control Study Evaluating the Genetic Factors Associated with the Development of Non-alcoholic Steatohepatitis (NASH) and genetic factors involved in the progression of Fatty Liver)
23rd November 2015 - ongoing
Status: In Recruitment
Specialism: Liver, Non-Alcoholic Fatty Liver Disease (NAFLD).
Non-alcoholic fatty liver diseases (NAFLD) includes a histological spectrum encompassing simple steatosis, with little potential to progress, and non-alcoholic steatohepatitis (NASH) that leads to cirrhosis in up to 20% of cases. Therefore, distinction of NASH from steatosis is an important step in stratification of patients for clinical management. Diagnosis of NASH relies upon the histological evaluation of liver biopsy; NASH is characterised by the presence of on-going hepatocellular injury represented by hepatocyte ballooning, with inflammation and varying levels of fibrosis in a background of triglyceride accumulation. Substantial hepatocyte death is a critical feature of liver injury associated with the progression of steatosis to steatohepatitis.
A number of factors are thought to contribute to the development of NASH from steatosis. Pathological mechanisms are suggested to involve changes to fatty acid metabolism, insulin resistance, oxidative stress, endoplasmic reticulum stress, increased gut permeability, alterations in cell signalling and cytokine production resulting in immunological responses, DNA damage, and inflammation.
Putative biomarkers of many of these processes have now been identified and can indicate levels of liver cell damage in a non-invasive manner in serum and urine samples. This study aims to determine whether genetic polymorphisms in components of some of these pathways are associated with an increased risk of developing NASH. It will also investigate whether genetic variation is associated with changes in potential disease biomarkers that can be non-invasively quantified and whether these biomarkers are valuable in diagnosing NASH.
Principle Research Question:
Are genetic polymorphisms associated with the development of non-alcoholic steatohepatitis (NASH)?
Measurable End Points:
- Frequency of variant alleles in patients with NASH compared with that in subjects with simple fatty liver or healthy controls.
- Association of genetic differences in patients and controls with non-invasive putative disease biomarkers.
- Correlation of biomarkers with the development of NASH.
|Professor Guruprasad Aithal||Professor Aithal has been a Consultant Hepatobiliary Physician at Nottingham University Hospitals NHS trust since 2001. He is the Head of the NIHR Nottingham Digestive Diseases Biomedical Research Centre, and the Head of Division for the Nottingham…|
|Dr Jane Grove||I am a research scientist in the Hepatology Group (Guru Aithal & Neil Guha) in the NIHR Nottingham Digestive Diseases Biomedical Research Unit. I am involved in translational research in the following areas: Drug-induced liver injury (assessment,…|