Scientists at the Basque Center for Cooperative Research in Biosciences (CIC bioGUNE) and OWL Genomics Ltd. (Bilbao, Spain), in collaboration with researchers at the INSERM and University Hospitals (APHP Pitié Salpêtrière Hospital, Pierre & Marie Curie University Paris and Centre Hospitalier Universitaire Nice, University of Nice-Sophia-Antipolis, Nice, France), Vanderbilt University (Nashville, US), the University of Southern California (Los Angeles, US), Clinic Hospital and IDIBAPS (Barcelona, Spain) and the Alcalá de Henares University (Alcalá de Henares, Spain) have used metabolomics technology to develop a blood test for non-alcoholic fatty liver disease (NAFLD) diagnosis. This research, which is part of the HEPADIP (www.hepadip.org) and CIBERehd (www.ciberehd.es) projects, supported by the European Commission and the Carlos III Health Institute in Spain, has been recently published (August 4) in The Journal of Proteome Research. OWL Genomics Ltd. is beginning to commercialize this new test in Spain.
Obesity posses a major risk factor for NAFLD. NAFLD is a progressive disease, ranging from the simple accumulation of fat in the liver (steatosis) to the more severe necroinflammatory complication non-alcoholic steatohepatitis (NASH), affecting up to 24% of the US and European population. Although only a small fraction of NAFLD patients develop cirrhosis and hepatocellular carcinoma (HCC), rising obesity prevalence may result in a corresponding increase in these more severe diseases, representing a major health risk. Therefore, early diagnosis is critical for the identification of NAFLD patients, disease progression risk assessment, and monitoring the response to treatment.
Currently, the most common methods for NAFLD diagnosis include imaging techniques such as ultrasound and magnetic resonance imaging, and the histological examination of a liver biopsy specimen. However, imaging techniques are expensive and non-specific (they are unable to distinguish NASH from simple steatosis), whilst liver biopsy is an expensive, invasive and subjective procedure, associated with potential complications and prone to sampling error.
The metabolomics-based blood test developed by OWL Genomics and CIC bioGUNE can distinguish between simple steatosis and NASH. “Results from this blood test could help clinicians diagnose NAFLD and inform on how a patient is responding to treatment”, says Professor José Mato, director of CIC bioGUNE and CIBERehd researcher. “We believe this is the first application of a novel experimental approach for blood metabolomic profiling that can identify biomarkers for potentially any liver disease and a superb example of translational research”, adds José Mato.
Genetically modified mouse model
In a report on the work by Barr et al., published in the August 4, 2010 issue of The Journal of Proteome Research, the scientists used a genetically modified mouse model, which spontaneously develops fatty liver, to carry out parallel metabolic profiling studies in human and mouse blood. Using this approach, a set of common biomarker metabolites in human and mouse NAFLD was identified. This blood NAFLD metabolic signature includes free fatty acids, phospholipids and bile acids.
After establishing this blood NAFLD metabolic signature, scientists focused in the identification of biomarkers discriminating between human steatosis and NASH. Using blood samples from biopsy proven steatosis and NASH patients, scientists identified several biomarkers discriminating between these two liver conditions. This list of blood NASH biomarkers includes further phospholipid subclasses (diacylglycerophosphocholine and ether glycerolphospholipids) and arachidonic acid. “This is the first serum global metabolite profiling study correlating with biopsy proven steatosis and NASH histology in a BMI matched, nondiabetic human population” says Jonathan Barr, head of the research team at OWL Genomics.