3×10-9, odds ratio = 5.3). This variant has previously been associated in multiple large genome-wide studies with hepatic steatosis, fibrosis and related phenotypes. Further comparisons identified other promising candidates (Table 1) but these did not reach significance after multiple test correction. Conclusion: Identification

of the known PNPLA3 Selleckchem Opaganib risk variant despite a very small sample size suggests accurate phenotyping and supports the use of an extreme phenotype design in NAFLD. Future expansion of the sample size is likely to identify further key causal genetic variants contributing to advanced fibrosis from NAFLD using this approach. Disclosures: Thomas J. Urban – Patent Held/Filed: Schering Plough Manal F. Abdelmalek – Consulting: Islet Sciences; Grant/Research Support: Mochida Pharmaceuticals, Gilead

Sciences, NIH/NIDDK, Synageva, Genfit Pharmaceuticals David B. Goldstein – Advisory Committees or Review Panels: Astra Zeneca, NIH, Biogen, Gordon Research Conference; Board Membership: Knome; Consulting: glaxo smithkline, Severe Adverse Events Consortium, Roche, Gilead Sciences, Inc, Scienta Advisors; Employment: Duke University; Grant/Research Support: UCB, NIH, Biogen, Henry M Jackson Foundation, SAIC, Inc, Bill & Melinda Gates Foundation, Eisai, Inc; Patent Held/Filed: patent IL28B findings, patent ITPA findings, Merck & Company; GDC-0973 clinical trial Speaking and Teaching: Current Biology magazine, Illumina, Regeneron, Dermatology Society; Stock Shareholder: Pfizer Anna Mae Diehl – Consulting: Roche; Grant/Research Support: Gilead, Genfit The following people have nothing to disclose: Cynthia A. Moylan, Matthew Rein Background

& Aims: Fibroblast growth factor 21 EGFR inhibitor (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. Circulating FGF21 levels are closely correlated with hepatic fat content in multiple disease conditions. Hepatic fat accumulation is a hallmark of alcoholic liver disease (ALD). We sought to determine the role of FGF21 in hepatic ste-atosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Methods: Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recom-binant human FGF21 for the last 5 days. Liver tissues were collected and examined for histologic alterations, liver fat and the corresponding gene and protein expression. Primary mouse hepatocytes and H4IIE cells were incubated with metformin or recombinant FGF21 protein. Genes and the products involved in in situ lipogenesis and fatty acid p-oxidation were analyzed. Results: Alcohol exposure increased circulating levels and hepatic expression of FGF21.