Plasma and stool metabolomic biomarkers of non-alcoholic fatty liver disease in Argentina

FLAVIA MAZZINI; FRANK COOK; JOHN GOUNARIDES; SEBASTIÁN MARCIANO; LEILA HADDAD; ANA JESICA TAMAROFF; PAOLA CASCIATO; ADRIAN NARVAEZ; MARIA FLORENCIA MASCARDI; MARGARITA ANDERS; ORLANDO NICOLAS FEDERICO OROZCO GANEM; NICOLAS QUIROZ; MARCELO RISK; SUSANA GUTT; ADRIAN GADANO; CELIA MENDEZ GARCIA; MARTIN MARRO; ALBERTO PENAS STEINHARDT; JULIETA TRINKS

Congreso; The Liver Meeting Digital Experience; 2020

American Association for the Study of the Liver Disease (AASLD)

Background: Non-invasive biomarkers are urgently needed to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk of disease progression, particularly in high prevalence areas such as Latin America. In this regard, targeted metabolomics is a powerful technology for discovering new gut microbiome-derived metabolites. Thus, we aimed to identify potential metabolomic biomarkers related to NAFLD stage in Argentina, and to assess their relationship with clinical and host genetic factors. Methods: Adult healthy volunteers (HV) and biopsy-proven simple steatosis (SS) or non-alcoholic steatohepatitis (NASH) patients were recruited. Demographic, clinical and food frequency consumption data, as well as plasma and stool samples were collected. SNP rs738409 (PNPLA3 gene) was determined in all volunteers. HPLC and flow injection analysis with MS/MS in tandem was applied for metabolomic studies using the MxP Quant 500 Kit (Biocrates Life Sciences AG, Austria). Significantly different metabolites among groups were identified with MetaboAnalyst v4.0. Bivariate and multivariate analyses were used to identify variables that were independently related to NAFLD stage. Forward stepwise logistic regression models were constructed to design the best feature combination that could distinguish between study groups. Receiver Operating Characteristic (ROC) curves were used to evaluate models? accuracy.Results: 19 HV, 12 SS and 22 NASH patients were recruited. Diet was similar between groups. The concentration of 33 out of 424 detected metabolites (25 in plasma and 8 in stool) was significantly different among study groups. Levels of triglycerides (TG) were higher among NAFLD patients, whereas levels of phosphatidylcholines (PC) and lysoPC were higher among HV. The PNPLA3 risk genotype for NAFLD and NASH (GG) was related to higher plasma levels of eicosenoic acid FA(20:1) (p