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Master Thesis

Diagnostic non-invasif des stéatohépatites non alcooliques : évaluation de nouveaux candidats biomarqueurs plasmatiques

Abstract : NAFLD has become a Public Health problem in developed countries. Liver biopsy remains the controversial gold standard examination. Alternatives lack specificity. There is a clear need for circulating biomarkers. Our main objective was to evaluate some biomarker candidates in human plasma for assessing the severity of NAFLD, in particular discriminating NASH from steatosis. We have selected 4 biomarker candidates (BHMT1, ADH1B, ADH4, CK18) from omics databases, literature searches and previous investigations. Concentrations of the candidates have been determined in 53 plasmas from biopsy-proven NAFLD patients thanks to immunoassays. Two subgroups were defined according to SAF score. Orthogonal analyses thanks to targeted proteomics are about to be finished. Quantification of CK18 with ELISA confirmed literature data, with higher plasmatic concentrations among significant disease group compared to mild disease group, for total as well as caspase-cleaved CK18 (respectively p=0.0001; p=0.0004). Both CK18 are correlated with necroinflammatory parameters, steatosis and fibrosis. BHMT1 was not quantifiable by immunoassay. No difference has been observed between 2 subgroups in terms of ADH1B and ADH4 plasma levels. Results from LC-MS/SRM are only preliminary. Total CK18 and CK18 fragments are serious candidate biomarkers for assessing NAFLD severity, including discriminate NASH from NAFL. Regarding BHMT1, ADH1B and ADH4, results from targeted proteomics are long awaited. Larger-scale studies are necessary to confirm these preliminary results.
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Master Thesis
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Submitted on : Tuesday, October 25, 2016 - 10:45:26 AM
Last modification on : Wednesday, July 15, 2020 - 8:58:04 AM


  • HAL Id : dumas-01387098, version 1


Justine Barthelon. Diagnostic non-invasif des stéatohépatites non alcooliques : évaluation de nouveaux candidats biomarqueurs plasmatiques. Médecine humaine et pathologie. 2016. ⟨dumas-01387098⟩



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