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1262A AASLD ABSTRACTS HEPATOLOGY, October, 2015<br />

hypertension, fasting plasma insulin and vitamin B12. In contrast,<br />

the fibrosis score was higher by 1.4 units in the high<br />

folate group (RBC folate > 620 ng/ml) compared to low folate<br />

group (p=0.003) in patients with the homozygous group. The<br />

fibrosis score increases by 0.06 units for every 25mg increase<br />

in serum folate level in homozygous group (p=0.014). Plasma<br />

vitamin B12 was not associated with histological severity. Conclusions.<br />

While folate has a protective effect on ballooning and<br />

the overall NAS score in NAFLD, in those NAFLD patients with<br />

the MTHFR homozygous mutation high folate levels had more<br />

advanced fibrosis. Despite the reported decreased activity of<br />

mutated MTHFR, folate supplementation may contribute to progression<br />

of fibrosis and should be used with caution.<br />

Disclosures:<br />

The following authors have nothing to disclose: Jaividhya Dasarathy, Rony Varghese,<br />

Iryna Kalinina, Rocio Lopez, Arthur J. McCullough, Srinivasan Dasarathy<br />

2163<br />

The Lipidomic Signature Of Disease Progression In Nonalcoholic<br />

Fatty Liver Disease (NAFLD)<br />

Cristina Alonso 1 , Amon Asgharpour 2 , Ibon Martinez-Arranz 1 ,<br />

Puneet Puri 2 , Mohammad S. Siddiqui 2 , Pablo Ortiz 1 , Jose M.<br />

Mato 3 , Arun J. Sanyal 2 ; 1 OWL, Derio, Spain; 2 VCU Medical Center<br />

Richmond, Division of Gastroenterology and Hepatology, Richmond,<br />

VA; 3 CIC bioGUNE, Ciberehd, Derio, Spain<br />

BACKGROUND:NAFLD includes a spectrum of histological<br />

phenotypes which can progress to cirrhosis at variable rates.<br />

While fibrosis assessment with a liver biopsy is the gold standard<br />

for assessment of disease progression it is limited by<br />

sampling variability and its invasive nature. There is therefore<br />

a major unmet need to identify a signature of disease progression<br />

that does not rely on a liver biopsy. Metabolomics<br />

provides an unbiased approach to obtain an assessment of<br />

whole-body metabolic response to disease progression. Previous<br />

attempts to describe a lipid signature focused on fatty liver<br />

vs.NASH (Hepatol 2009,50:1827, J Prot Res 2012,11:2521,<br />

J Lipid Res 2015,56:185) or NASH vs.cirrhosis (J Lipid Res<br />

2015,56:722). The lipidomic signature of disease progression<br />

over earlier stages remains unknown. AIM:To characterize<br />

the changes in the circulating lipidome with disease<br />

progression from no fibrosis to advanced fibrosis in subjects<br />

with NAFLD. METHODS:Plasma samples collected at the time<br />

of liver biopsy were analyzed by UPLC-MS. Specifically, amino<br />

acids, fatty acyls, bile acids, glycerolipids, glycerophospholipids,<br />

sterols and sphingolipids were analyzed. RESULTS:<br />

11controls, 29NAFLD with no fibrosis, 43NAFLD with early<br />

stage fibrosis (stage1-2) and 22NAFLD with advanced fibrosis<br />

(stage3-4) were studied. 22metabolites were associated<br />

with disease progression (Figure). While cholesteryl esters and<br />

phosphatidylcholines, decreased with the progression [t-test<br />

Control vs.NAFLD with no fibrosis; early stage or advanced<br />

fibrosis: PC(O-24:1/0:0) and PC(18:2/20:4):p

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