310 Role of Polyunsaturated Fatty Acids Consumption on Development of NAFLD in Hispanic USA Population

the role of ficolins in the pathogenesis of NAFLD. Methods: Sera from patients with biopsyproven NAFLD were tested for the ficolin levels (ug/ml) using Enzyme Linked Immunosorbent Assay (ELISA). NAFLD patients were grouped based on liver histology to NASH, Non-NASH NAFLD and no liver disease. Statistical analysis was performed to draw associations of ficolin levels and the different variables using uni- and multivariate analysis. P-values ≤0.05 were considered to be potentially significant. Results: The study cohort includes 147 subject (biopsy-proven NAFLD N=98 and controls without liver disease N=49). The demographic characteristics and the prevalence of important histological features in NAFLD patients are summarized in Table 1. Patients with NAFLD had significantly higher levels of H-ficolin: Median (IQR): 49.0(36.9-65.7) as compared to the healthy controls 39.7(30.8-51.2), P= 0.003. Furthermore patients with histologic NASH: 59.4(43.7-80.1) had significantly higher level of H-ficolin as compared to Non-NASH NAFLD: 44.4(36.4-56.2), P=0.002. There was no significant difference of L-Ficolin level between histologic NASH: 1.1(0.8-1.5) and NonNASH NAFLD: 1.1(0.8-2.1), P=0.25. Interestingly, the levels of H-ficolin positively correlated with Steatosis (ρ=0.24, P=0.01), Inflammatory Cells ( ρ=0.20, P=0.04), Kupffer cells ( ρ= 0.24, P=0.01), Focal Necrosis ( ρ=0.29, P=0.002), Degenerative Ballooning ( ρ=0.25, P= 0.009), Pericellular Fibrosis (ρ=0.28, P=0.003), and Advanced Fibrosis ( ρ=0.21, P=0.03). Furthermore, H-ficolin correlated positively with BMI, ( ρ=0.19, P=0.02) and negatively with HDL (ρ=-0.30, P=0.002). After controlling for potential confounders, in multivariate analysis, H-ficolin was found to be independently prognostic for NAFLD Odds Ratio (OR): [1.04(1.011.06), P=0.002] and NASH progression (OR): [1.04(1.01-1.07), P=0.004] Conclusions: In patients with NAFLD, H-ficolin is associated with NASH and individual histological features of NASH. This may indicate that H-ficolin may play an immunomodulatory role in the pathogenesis of NASH.

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AASLD Abstracts

Role of Intestinal Permeability for Metabolic Disturbances After Fructose Overconsumption. Christian Kienbacher, Werner Dolak, Stefan Traussnigg, Petra Steindl-Munda, Karl Oettl, Vanessa Stadlbauer, Sylvia Knapp, Harald Vogelsang, Michael H. Trauner Background and Aims: Fructose overconsumption in Western diet is linked to non-alcoholic fatty liver disease (NAFLD). In animal models fructose overconsumption leads to chronic metabolic low-grade inflammation and was also linked to cardiovascular disease (CVD) as well as development of type-II-Diabetes (T2DM). Until now, the impact of fructose overconsumption is often studied in overweight, T2DM or NAFLD patients, but is not as well described in healthy subjects. To test our hypothesis that fructose overconsumption may impact on the gut-liver axis by increasing intestinal permeability, bacterial translocation, and consecutively metabolic inflammation as important mechanisms in the pathogenesis of NAFLD, CVD and T2DM, we examined the impact of a high oral fructose challenge (150g/ day for 4 weeks) on intestinal permeability and inflammation. Methods: Ten healthy volunteers were enrolled (m:f=5:5; median[range] age=24.5[21-37] [years]; p=n.s.). Intestinal permeability was assessed by sucrose-lactulose-mannitol (SLM) test using high performance liquid chromatography of urine collected over 5 hours. Interleukin-6 (IL-6) was assessed by ELISA. C-reactive Protein (CRP) and Fibronectin were assessed using nephelometry. Results: After the oral fructose challenge changes in energy metabolism reflected by increased BMI (mean±SD 21.11±2.68 vs 21.51±2.77 [kg/m^2]; p<0.001) as well as fasting glucose levels (mean±SD 83.2±8.37 vs 88.4±5.48 [mg/dL]; p=0.035) were observed. Gastroduodenal permeability, reflected by recovered sucrose (median[range] 0.075[0-0.1] vs 0.089[0-0.1] [mmol/L]; p=0.68) as well as small intestinal permeability reflected by lactulose/mannitolratio (mean±SD 0.021±0.006 vs 0.019±0.008 [%]; p=0.622) remained stable. In line, inflammatory parameters CRP (median[range] 0.5[0-3] vs 0[0-1] [mg/dL]; p=0.066) and Fibronectin (mean±SD 35.3±8.63 vs 35.3±7.73 [mg/dL]; p=1.0) remained unchanged. IL-6 was below the detection limit prior and after fructose challenge, suggesting a high oral fructose challenge does not affect intestinal permeability in healthy young volunteers. Conclusion: Healthy young volunteers are capable of handling fructose overconsumption (150g/day for 4 weeks) on top of their normal diet without any increase in intestinal permeability or inflammation. This further supports the hypothesis that fructose overconsumption may act as "hepatotoxin" as a second hit in pre-existing metabolic diseases and/or on top of genetically predisposing backgrounds such as PNPLA3 genotype. Acknowledgements: The research leading to these results has received funding from the Medical Scientific Fund of the Mayor of the City of Vienna (grant number 12040).

Table 1: Demographic and Clinical Characteristics of The Study Cohort 310 312

Role of Polyunsaturated Fatty Acids Consumption on Development of NAFLD in Hispanic USA Population Ghulamullah Shahzad, Huafeng Shen, Mahreema Jawairia, Paul Mustacchia

Advanced Disease With Faster Progression in Patients With Alcoholic Liver Disease Compared to Non-Alcoholic Steatohepatitis Mohamed G. Shoreibah, Evan Raff, Donny D. Kakati, Khalid Rasheed, Joseph R. Bloomer, Ashwani K. Singal

Background: Hispanic population living in the United States demonstrates particular variations in epidemiology, natural history, and response to therapy of chronic liver disease. Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in Hispanic population followed by chronic alcoholic liver disease and viral hepatitis C and B. Multiple studies have shown that NAFLD is more common in Hispanics than in Caucasians or Africans. Although multiple environmental risk factors may be responsible for ethnic variations in NAFLD, Here we propose that increase polyunsaturated fatty acid (PUFA) consumption might have association with NAFLD especially among Hispanics. Method: We included 11,416 adults aged 20-74 participating in the Third National Health and Nutrition Examination Survey (NHANES III). Of those, 2,889 individuals were identified as NAFLD and 8,527 were used as controls. The estimate fatty acids consumptions during the 24-h period prior to the interview were obtained by dietary recall. Logistic regression model was used to investigate the association between fatty acids consumption and NAFLD after controlling the potential confounders. All analyses were performed using SAS 9.3 (SAS Institute Inc., Cary, NC, USA). Results: In multivariate analysis, there was no significant association between any type of fatty acids consumption and NAFLD in the whole study population. However, after dividing the population into different race/ethnicity groups, we found NAFLD was significantly associated with total PUFA consumption (gm) (OR = 1.10, p = 0.01) and linoleic acid consumption (gm) (OR = 1.13, p = 0.005) in the MexicanAmerican population. This effect was especially strong in the Mexican-American males (OR = 1.14, 95% CI 1.05 - 1.23, p = 0.003). Conclusions: Total PUFA and linoleic acid consumptions were found to significantly increase the risk of NAFLD in Mexican-American population, especially in Mexican-American males. Discussion: NAFLD is a clinically relevant chronic liver disease that may lead to liver impairment and cirrhosis. Over the past years, several therapeutic proposals have been tested, but a validated and unique approach has not yet been obtained. Role of Polyunsaturated fatty acids (PUFAs) on liver inflammation and development of NAFLD depend on their structure. Polyunsaturated n 6 PUFAs, such as linoleic acid and arachidonic acid, are precursors to potent proinflammatory eicosanoids. In contrast role n 3 PUFAs, such as αlinolenic acid, eicosapentaenoic acid and docosahexaenoic acid, have an important anti-inflammatory role; they decrease lipogenesis and increase fatty acid oxidation, leading to a reduction in hepatic steatosis. The results of this preliminary study showed that long-term consumption of PUFA resulted in increase in NAFLD particularly among Mexican Americans males.

Background and aims: Steatohepatitis is a common cause of liver disease due to alcohol (ALD) or non-alcoholic steatohepatitis liver disease (NASH). Both diseases are potentially reversible if detected early. However data comparing clinical presentations of ALD and NASH are scant. Methods: We performed a retrospective analysis of patients with ALD or NASH managed at our center from 2007 to 2011. ALD was diagnosed by excluding liver diseases (except HCV) and alcohol abuse of >40 g/d in women and >60 g/d in men for >5 years. NASH was diagnosed by excluding other liver diseases and a history of alcohol use of <10 g/d. Chi-square and unpaired t-test were used for comparing categorical and continuous variables respectively. Odds ratio (OR) with 95% CI interval; was reported for logistic regression analysis. Kaplan Meier curves were generated for comparing survival outcomes with Log Rank test used for analysis. P value <0.05 was considered significant. Results: Patients with ALD (N=206; mean age 51 y; 68% males; 23% diabetic) compared to NASH (N=401; mean age 50 y; 45% males; 56% diabetic) were more likely to present with cirrhosis or its complications (88% vs. 54%; P<0.0001). MELD score (mean ± SD) was higher in ALD compared to NASH (13±7 vs. 8±8; P<0.0001) patients. Diagnosis of cirrhosis or its complications were predictive of ALD by over 3-fold (3.3 [1.3-8.2]) and over 2 fold (2.4 [1.24.7]), respectively. Excluding patients with cirrhosis at or within 6 months of presentation, development of cirrhosis was more often and faster in ALD patients compared to NASH (61%vs.25%, median time to cirrhosis: 24 vs.40 mo. respectively; P<0.0001). Similarly, excluding patients with cirrhosis complications at or within 1 month of presentation, more ALD patients developed complications compared to NASH patients with shorter time to respective event: ascites (46%vs.24%; median time: 37vs.40 mo.; P<0.001); Hepatic encephalopathy (31%vs.20%; median time 32 vs.43 mo. ; P=0.03); variceal bleed (13%vs.7%; median time: 32 vs. 46 mo. P=0.004); and hepatocellular carcinoma (11%vs.7%; median time: 32 vs.43 mo.; P=0.0004). On a median follow-up of 33 mo. in ALD and 46 mo. in NASH, 35 patients died (19 ALD) with worse survival in ALD patients (96% vs. 91%; P=0.004). Conclusion: Compared to non-alcoholic steatohepatitis, patients with alcoholic liver disease are more likely to present with advanced liver disease with faster development of cirrhosis and its complications on follow-up. It is unclear whether these differences are due to variations in the natural history of diseases or to their referral pattern. Further studies are needed to a) identify possible barriers referral of patients with alcoholic liver disease at an earlier stage and b) develop and implementation of strategies to overcome these barriers to improve outcome of patients with alcoholic liver disease.

311 Human H-Ficolin Is Independently Associated With Non Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH) Azza Karrar, Sneha Lingam, Elena Younossi, Sharon L. Hunt, Zahra Younoszai, Maria Stepanova, Zachary D. Goodman, Zobair M. Younossi Background and Aim: The role of the innate humoral immune response in the development of NAFLD is not clear. H-ficolin and L-ficolin are acute phase proteins/lectins secreted by cells to activate the complement system in humoral innate immunity. Our aim was to assess

AASLD Abstracts

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