Taken together, our data suggest NKT cells play a critical role in the development of early alcoholic

liver injury, neutrophil recruitment, click here and inflammation. Future studies will be aimed at elucidating the mechanism(s) by which ethanol activates NKT cells and further investigating how activated NKT cells modify the critical inflammatory pathways involved in progression of ALD. Disclosures: The following people have nothing to disclose: Stephanie Mathews, Dechun Feng, Bin Gao Background: A PNPLA3 gene polymorphism (rs738409) is associated with liver fat content and histological severity in nonalcoholic fatty liver disease and with alcoholic cirrhosis. However the relationship between PNPLA3 genotype and acute alcoholic hepatitis (AAH), a distinct form of severe alcoholic liver disease, is unknown. The goal of this study was to determine whether rs738409 is associated with AAH and with differences in disease severity. Methods: We prospectively enrolled 46 patients admitted with severe AAH [Maddrey Discriminant Function (DF) >32]. As controls, we used 204 patients with history of heavy alcohol use (>8 and 15 drinks per week for females and males, respectively)

but no known liver disease enrolled in the AZD9668 in vitro North American Pancreatitis Study (NAPS2). Clinical and biochemical measures were recorded. Median values were reported and nonparametric statistical tests utilized. PNPLA3 genotype in cases and controls was determined by real-time PCR. We compared allele and genotype frequencies between patients with AAH and controls using Fisher’s exact and Chi-Square tests. We compared markers of disease severity using Kruskal-Wallis test. Results: The G allele was more frequent in patients with AAH compared with controls (0.32 vs 0.19; p< 0.01). Of the patients with AAH, 46% had CC genotype, 43% had CG genotype, and 11% had GG genotype, compared with controls,

of which 67% had CC genotype, medchemexpress 27% had CG genotype, and 5% had GG genotype (p =0.02). Since AAH patients were predominantly male and Caucasian, we stratified the analysis by race and gender. Amongst Caucasian patients, 47% of AAH patients had CC genotype, 42% had CG genotype and 11% had GG genotype compared with 66% CC, 29% CG, and 6% GG (p = 0.056). Male AAH patients (n=34) had genotype frequencies of CC 41%, CG 50%, GG 9% versus male controls (n=100) with frequencies of CC 67%, CG 25%, and GG 8% (p=0.02). Female AAH patients (n=11) had genotype frequencies of CC 64%, CG 18%, GG 18% compared with female controls (n=105) with CC 68%, CG 29%, GG 3% (p = 0.05). To determine whether PNPLA3 gene variants were associated with disease severity in AAH, we determined Model for Endstage Liver Disease (MELD) scores on the first day of admission. Patients with GG genotype had higher MELD scores (MELD 31 in GG genotype versus MELD 26 in CC genotype; p < 0.05).