Magnetic resonance spectroscopy (MRS) Estimation of Glutathione flux in the Liver (MEGL)
1st August 2015 - ongoing
Team: Professor Guruprasad Aithal.
Fatty liver (NAFLD) has become a major health burden. Excess hepatic fat is associated with unresolved oxidative stress which generates inflammation and hepatocyte injury seen in non-alcoholic steatohepatitis (NASH). NASH is progressive leading to cirrhosis in 15% of patients and is an independent risk factor for cardiovascular outcomes.
Currently there are no methods to distinguish NASH from simple NAFLD or to estimate the burden of oxidative stress. This study aims to provide underpinning work to develop direct measures of oxidative stress in vivo. Glutathione is the primary anti-oxidant used in liver, and glutathione production directly reflects rates of oxidation and the ability of the liver to combat excess free radicals. Pilot work by our collaborators showed the potential of using an oral [2-13C]glycine intake to measure glutathione in liver using Carbon-13 Magnetic resonance spectroscopy (MRS). We aim to develop this pilot study by optimizing the scan technique to provide a clinical test and potential biomarker for progressive liver disease. This will assist in the stratification of patients with NAFLD and can be used to monitor patients’ progress in response to therapy.
We will initially work to optimize and develop MR protocol ex vivo. To test the healthy response, we will then run a matched pair in vivo study exploring hepatic anti-oxidant (glutathione) flux in 12 healthy subjects (powered from pilot data). This will involve regular oral intake of labelled [2-13C] glycine with intermittent 13C MRS scanning and also acquiring blood samples for glucose and peptide analysis. Subjects will be tested in fasted and postprandial states and the results compared.