Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver diseases (NAFLD) encompasses a spectrum of disease including 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.

Our research aims to identify biomarkers of these processes which can indicate levels of liver cell damage in a non-invasive manner in serum and urine samples. We are evaluating serum biomarkers of cell death as mechanistic indicators of NASH which may be of value in distinguishing NASH from NAFLD. We are also determining the role of various genetic variants (polymorphisms) in contributing to disease development.

The Metabolic Physiology Group in the School of Life Sciences is interested in dietary and lifestyle effects on health and disease. Particular interests involve obesity and diabetes, including factors contributing to the development of increased liver fat content and its effects on insulin resistance. The research involves the measurement of insulin sensitivity, carbohydrate, fat and protein metabolism including substrate turnover using stable isotope tracers, with studies performed on healthy volunteers, patients with obesity, NASH, diabetes, as well as surgical patients and other clinical conditions. The techniques used in these studies include muscle and adipose tissue biopsies (with associated metabolite, gene and protein expression), MR spectroscopy for muscle and liver glycogen and fat contents, as well as glucose clamps and glucose ingestion for insulin sensitivity, intravenous feeding, and tracer infusions. The lifestyle related interests range from physical activity and exercise programmes to inactivity and immobilisation achieved by limb immobilisation or prolonged bed-rest. Recent and current research projects include effects of glucose or fructose on liver fat content and insulin sensitivity, carnitine supplementation effects on muscle metabolism and insulin sensitivity, diet and exercise programmes in relation to diabetes prevention.

Research group members include: IA Macdonald, PL Greenhaff, K Tsintzas, MA Taylor, FB Stephens, EJ Simpson plus clinical collaborators and research fellows

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guruprasad-aithal Professor Guruprasad Aithal Biography Professor Guruprasad P. Aithal graduated with MBBS from Kasturba Medical College, Manipal, MD (Internal Medicine) from Bangalore Medical College, Bengaluru, India and completed his specialist training in Gastroenterology in the Northern…