: Return 2342

Notes

We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.

Application 9914

Determining the Outcomes of People with Liver Disease

Perspectum Diagnostics has developed a method of analysing magnetic resonance imaging (MRI) data that gives an accurate estimate of the amount of liver fat, the amount of liver iron, and the extent of inflammation and scarring in the liver. These three characteristics of the liver are also the most important in the diagnosis of liver disease. By analysing the abdominal MR images from all UK Biobank participants, we can determine approximately how many have abnormal liver composition, and the distribution of each of these measures in the population. Finally, and most importantly, we can examine the outcomes of the participants with liver disease, and determine which biomarkers are predictive of these outcomes. New, clinically meaningful data will be generated from the existing DICOM images, and fed back in to the UK Biobank data repository. These data will be directly relevant to future health outcomes and of use to other researchers. Excess liver fat is associated with coronary artery atheroma and metabolic syndrome, and is strongly associated with obesity-related disease. Liver fibrosis and inflammation are both associated with adverse outcomes, which is especially relevant in those with fatty liver disease. We will be able to show which patients have liver disease, and future researchers can link these findings to specific outcomes. The MRI scans from the imaging enhancement study will be analysed by LiverMultiScan to determine liver fat, iron, inflammation and fibrosis (LIF score). These measures have separately been validated against liver biopsies from patients. These data will then be compared to measures of body composition, serum markers (lipid profile, iron stores, CRP and others) and habits associated with liver disease (eg alcohol intake, exercise and diet). We will follow up all patients and identify those with a liver-related clinical outcome (eg liver failure, hepatic encephalopathy), and determine which prognostic factors best predict these outcomes in this population. All 100,000 participants from the UK Biobank imaging enhancement study (ie the full cohort from the imaging enhancement study) will be analysed to determine the baseline liver health profiles of the population. Clinical outcomes data will be collected, with the aim of capturing - every liver-related death - every episode of oesophageal variceal bleeding - every new diagnosis of cirrhosis - every new diagnosis of liver failure or gross ascites due to liver disease (excluding malignant ascites) - every new primary hepatocellular carcinoma and cholangiocarcinoma - every new pancreatic carcinoma

Lead investigator:	Dr Rajarshi Banerjee
Lead institution:	Perspectum Diagnostics Ltd

1 Publication

Pub ID	Title	Author(s)	Year	Journal
2343	Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis	Parisinos CA et al.	2020	J Hepatol

Application:	9914, Determining the Outcomes of People with Liver Disease
Title:	Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis
Size:	209952 B
Archived:	24 Aug 2020
Stability:	Accruing
Personal:	Contains individual-level data