Nature Medicine
10, 429 - 434 (2004)
Published online: 7 March 2004; | doi:10.1038/nm1006
Noninvasive diagnosis of liver cirrhosis using DNA sequencer−based total serum protein glycomicsNico Callewaert1, 4, Hans Van Vlierberghe2, Annelies Van Hecke1, Wouter Laroy1, Joris Delanghe3
& Roland Contreras11
Fundamental and Applied Molecular Biology, Department of Molecular Biomedical Research, Ghent University and VIB, Technologiepark 927, B-9052 Zwijnaarde, Belgium. 2
Department of Gastroenterology and Hepatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. 3
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. 4
Present address: Swiss Federal Institute of Technology (ETH), Schmelzbergstrasse 7, CH-8092 Zürich, Switzerland.
Correspondence should be addressed to Nico Callewaert natmedcontact@dmbr.Ugent.be or Roland Contreras natmedcontact@dmbr.Ugent.beWe applied our 'clinical glycomics' technology, based on DNA sequencer/fragment analyzers, to generate profiles of serum protein N-glycans of liver disease patients. This technology yielded a biomarker that distinguished compensated cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity and 86% specificity (100% sensitivity and specificity for decompensated cirrhosis). In combination with the clinical chemistry−based Fibrotest biomarker, compensated cirrhosis was detected with 100% specificity and 75% sensitivity. The current 'gold standard' for liver cirrhosis detection is an invasive, costly, often painful liver biopsy. Consequently, the highly specific set of biomarkers presented could obviate biopsy in many cirrhosis patients. This biomarker combination could eventually be used in follow-up examinations of chronic liver disease patients, to yield a warning that cirrhosis has developed and that the risk of complications (such as hepatocellular carcinoma) has increased considerably. Our clinical glycomics technique can easily be implemented in existing molecular diagnostics laboratories.
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