PLASMA AND STOOL METABOLOMIC BIOMARKERS FOR NON- ALCOHOLIC FATTY LIVER DISEASE IN ARGENTINA

MAZZINI, FLAVIA NOELIA; COOK, FRANK; GOUNARIDES, JOHN; MARCIANO, SEBASTIÁN; RISK, MARCELO; GADANO, ADRIÁN; PENAS STEINHARDT, ALBERTO; TRINKS, JULIETA

Congreso; AASLD 2020; 2020

Background: Non-invasive biomarkers are urgentlyneeded to identify patients with non-alcoholic fatty liverdisease (NAFLD) at risk of disease progression, particularlyin high prevalence areas such as Latin America . In thisregard, targeted metabolomics is a powerful technology fordiscovering new gut microbiome-derived metabolites . Thus,we aimed to identify potential metabolomic biomarkers relatedto NAFLD stage in Argentina, and to assess their relationshipwith clinical and host genetic factors . Methods: Adult healthyvolunteers (HV), biopsy-proven simple steatosis (SS) andnon-alcoholic steatohepatitis (NASH) patients were recruited .Demographic, clinical and food frequency consumption data,as well as plasma and stool samples were collected . SNPrs738409 (PNPLA3 gene) was determined in all volunteers .HPLC and flow injection analysis with MS/MS in tandemwas applied for metabolomic studies using the MxP Quant500 Kit (Biocrates Life Sciences AG, Austria). Significantlydifferent metabolites among groups were identified withMetaboAnalyst v4 .0 . Bivariate and multivariate analyses wereused to identify variables that were independently related toNAFLD stage . Forward stepwise logistic regression modelswere constructed to design the best feature combination thatcould distinguish between study groups . Receiver OperatingCharacteristic (ROC) curves were used to evaluate models?accuracy . Results: 19 HV, 12 SS and 22 NASH patients wereincluded in the study . Diet was similar between groups . Theconcentrations of 33 out of the 424 detected metabolites (25in plasma and 8 in stool) were significantly different amongstudy groups . Levels of triglycerides (TG) were higher amongNAFLD patients, whereas levels of phosphatidylcholines(PC) and lysoPC were higher among HV . The PNPLA3risk genotype for NAFLD and NASH (GG) was related tohigher plasma levels of eicosenoic acid FA(20:1) (p