000 02745na a2200229 4500
003 H12O
005 20180113072142.0
008 130622s2012 xxx||||| |||| 00| 0 eng d
040 _cH12O
041 _aeng
100 _aPérez Carreras, Mercedes
_91444
_eAparato Digestivo
245 0 0 _aObesity-Dependent Metabolic Signatures Associated with Nonalcoholic Fatty Liver Disease Progression
_h[artículo]
260 _bJournal of Proteome Research,
_c2012
300 _a11(4):2521-32.
500 _aFormato Vancouver: Barr J, Caballería J, Martínez-Arranz I, Domínguez-Díez A, Alonso C, Muntané J, et al. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012 Apr 6;11(4):2521-32.
501 _aPMID: 22364559
504 _aContiene 45 referencias
520 _aOur understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n = 90) or diagnosed with NAFLD (steatosis, n = 246; NASH, n = 131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.
710 _9273
_aServicio de Medicina del Aparato Digestivo
856 _uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321123/
_yAcceso libre
942 _n0
_2ddc
_cART
999 _c5080
_d5080