Novel method for detection of fatty liver disease receives international recognition

2010/9/23

A novel method for the early diagnosis of non-alcoholic fatty liver disease (NAFLD) was published this August in the Journal of Proteome Research. The new analysis test, based on metabolomics technology, was devised by a consortium of research centres, universities and business companies, and led by CIC bioGUNE and Owl Genomics. From this method a new efficacious tool will be developed and which will be shortly available, when OWL Genomics begins marketing the product in Spain.

Apart from CIC bioGUNE and Owl Genomics, the development of this novel project also involved the participación of INSERM and a number of university hospitals (Hospital APHP Pitié Salpêtrière, the Pierre y Marie Curie University in Paris, the University Hospital Centre in Nice and the Sophia-Antipolis University in the same French city, the Vanderbilt University in Nashville, USA, the University of South California (Los Angeles, USA), el Hospital Clínico and IDIBAPS (Barcelona) and the University of Alcalá de Henares in Spain). Likewise, HEPADIP (www.hepadip.org) and CIBERehd (www.ciberehd.es) form part of the projects and have the support of the European Commission and the Carlos III Institute of Health (Spain).

Obesity is a serious risk factor in NAFLD, a progressive disease that goes from the simple accumulation of fat in the liver (steatosis) to more severe necroinflammatory complications such as non-alcoholic steatohepatitis (NASH), affecting 24% of the US and European population. While only a small number of patients suffering from NAFLD develop cirrhosis and hepatocellular carcinoma (HCC), the increasing tendency to obesity could give rise to an increase in the rate of these, more serious, diseases, which represent a greater risk to health. This is why early diagnosis is crucial for identifying patients with NAFLD, in order to evaluate the risk of the disease progressing and to monitor the response to treatment.

The most commonly employed methods for diagnosing NAFLD today are those involving ultrasounds and magnetic resonance imaging techniques, and the histological examination of a liver biopsy sample. Nevertheless, imaging techniques are expensive and not very precise (not being able to differentiate between a NASH and a simple steatosis), while the liver biopsy is an expensive and invasive technique with a subjective procedure associated with potential complications and prone to sampling errors.

The metabolomics-based blood analysis devised by OWL Genomics and CIC bioGUNE does detect the difference between a simple steatosis and NASH. «The results of these blood analyses can help health care professionals to diagnose NAFLD and tell how the patient is responding to treatment», stated José Mato, Director of CIC bioGUNE and researcher at CIBERehd. «We believe that this is the first application of a new experimental approach to determine a metabolomic profile of the blood, thus providing identification of possible biomarkers for any liver disease and constituting a magnificent example of translational research », added Mr Mato.

Type of genetically modified mouse

In order to carry out the work published in the Journal of Proteome Research, the scientists used a type of genetically modified mouse that developed a fatty liver spontaneously, and so parallel studies could be undertaken and the metabolic profile of both human and mouse blood could be determined. Making use of this approach, a series of metabolite biomarkers in NAFLD common to humans and mice was identified. This metabolic footprint of NAFLD in the blood includes free fatty acids, phospholipids and biliary acids.

After establishing the metabolic footprint of NAFLD in the blood, the scientists focused on the identification of biomarkers that distinguish human steatosis and NASH. Using blood samples taken from biopsies of patients with steatosis and NASH, the scientists identified various biomarkers that distinguish these two different conditions of the liver. This list of biomarkers of NASH in the blood includes other subtypes of phospholipids (diacylglycerol phospholipids and ether glycerophospholipids) and arachidonic acid. «This is the first global serological study determining metabolites that establishes a link between steatosis demonstrated through biopsy and NASH histology for a non-diabetic human population with a similar body mass index», stated Mr Jonathan Barr, head of the OWL Genomics research team.

Source