by using the plasma PTX3 levels, AST, ALT, type IV collagen 7s domain, hyaluronic acid, which were significantly elevated factors in NASH patients than in non-NASH patients by the univariate analysis. Plasma PTX3 level was still significant in the NASH patients as compared with that in non-NASH patients by multiple logistic regression analysis. Conclu- sions: This is the first study to demonstrate consistent and profound elevation of plasma PTX3 levels in NASH in comparison with non-NASH. The results suggest that plasma PTX3 levels may not only be laboratory values that differentiate NASH from non-NASH, but marker of the severity of hepatic fibrosis in NASH. Plasma PTX3 may be useful for targeted therapy against fibrosis in NASH patients. T1006 Public Awareness and Attitudes Towards Non Alcoholic Fatty Liver Disease (NAFLD) Nan Sandar, Vishal Ghevariya, Kishor V. Patel, Zeyar Thet, Nehal Ghevariya, Mojdeh Momeni, Sury Anand Background & Aims: NAFLD is the most common cause of elevated transaminases and cirrhosis of liver. It poses a significant health burden worldwide. In the United States, chronic liver disease and cirrhosis are the 10th leading cause of death. The pathophysiology, diagnosis and treatment of NAFLD have been intensively investigated but public awareness of NAFLD is unknown. This study is to determine awareness of NAFLD and its risk factors in the general population. Methods: From March to July 2008, members of the research group conducted a written survey with 5000 non-institutionalized residents of Brooklyn, NY. All participants were age 18 and older. Sixteen items were included in the survey questionnaire. Results: Overwhelming majority (98%) of the subjects stated that their physicians never had a discussion of NAFLD with them. Respondents of < 20 year of age reported significantly less interaction with their physicians (P < 0.001). Seventy percent of the subjects believed that NAFLD is hereditary and only two percent recognized NAFLD was preventable. Eighty three percent did not know the risk factors that can lead to fatty liver and only one percent thought that lack of exercise could lead to NAFLD. Ninety five percent did not recognize that fat in the liver could cause serious health problems and only two percent acknowledged fatty liver could progress to cirrhosis. Ninety three percent of the subjects were not sure how NAFLD was diagnosed. There was no statistical difference regarding knowledge and attitude towards NAFLD and its risk factors regardless of age, gender or educational statu- s.Eighty percent had never heard of cirrhosis and Eighty five percent of the study population were not aware of risk factors for cirrhosis. Participants with a lower education level (high school or less) were more aware of cirrhosis when compared to subjects with advanced degrees (P < 0.0001) and knew that alcohol was linked to cirrhosis (P < 0.0001). A similar percentage of subjects with higher education thought that alcohol and hepatitis could lead to cirrhosis. Conclusion: Public awareness of fatty liver, its risk factors and complications are poor and there is suboptimal interaction between physicians with their patients in discussing this condition. Awareness of NAFLD must be promoted for prevention, early detection and treatment. Active participation of primary care physicians, pediatricians and other health care personnel in counseling their patients regarding NAFLD is a critical piece in a preventive strategy which will include life style modification. Educational tools including mass media could also be helpful in increasing awareness of NAFLD. T1007 Sexual Development and Its Influence On Regional Anthropometric Measures and Histologic Features Among Pediatric Patients with NAFLD Ayako Suzuki, Manal F. Abdelmalek, Cynthia D. Guy, Jeffrey Schwimmer, Joel E. Lavine, A O. Scheimann, Anna Mae Diehl Background: During puberty, changes in sex hormones alter body composition and impact lean body mass, energy expenditure and regional fat distribution. For instance, both estrogen and androgen promote site-specific fat accumulation in white adipose tissue (subcutaneous vs. intra-abdominal); therefore, fat storage capacity of white adipose tissue may increase along with sexual development, which then could decrease ectopic fat accumulation of excess energy (e.g., steatosis and intramuscular fat deposit) and beneficially influence NAFLD histology. Aim: Our aim was to determine the associations of sexual development with anthropometric measures and the histologic features of NAFLD in children (age ≤ 18 years). Methods: A cross-sectional analysis of 218 children (girls 51, boys 167) with NAFLD whose clinical data were obtained within 6 months from liver biopsy (baseline data from TONIC and Database of NASH CRN) was performed. First, the circumferences of waist (WAIST), hip (HIP), and middle upper arm (ARM) and triceps skinfold were compared by Tanner stage (and menarche for girls). Analyses were performed separately for boys and girls using multiple linear regression models. Then, the grade of steatosis, lobular and portal inflammation, ballooning, and fibrosis stage were associated with Tanner stages using χ2 test and multiple ordinal logistic regression (OLR) models. Results: After adjusting for age, height, weight, caloric intake, and physical activity (met), skinhold was significantly larger in boys with Tanner stages 2-5 vs. stage 1 (β=4.6+2.0, p<0.05) and tended to be larger among girls after menarche (β=9.3+4.8, p=0.065, with adjusting for Tanner stage). No gender differences in the histologic features of NAFLD were observed (χ2 test). In the entire population, Tanner stage (1 vs. 2-4 vs. 5) was associated with grades of steatosis (grade 3 was: 46%, 43%, and 24% respectively, p<0.03) and tended to be associated with grade of portal inflammation (grade 2 was: 17%, 7%, and 10% respectively, p=0.07). In the OLR models adjusting for age, gender, BMI, and QUICKI, Tanner stage 2-4 (pubertal) and 5 (post-pubertal) were more likely associated with lower histologic grades of steatosis (OR= 2.5, p<0.03 and OR=10.1, p<0.001 respectively) compared to Tanner stage 1 (pre-pubertal). Conclusion: Sexual development (i.e., Tanner stage and menarche) appeared to be associated with: 1) increased subcutaneous fat deposition and 2) less severe steatosis among pediatric patients with NAFLD. Further investigation is warranted to delineate whether sex hormones influence other histologic features of NAFLD in pediatric patients in a larger population. A-845 AASLD Abstracts T1008 Insulin Sensitizers for the Management of Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials Abhishek Choudhary, Nicholas M. Szary, Matthew L. Bechtold, Srinivas R. Puli, Scott Rector, John P. Thyfault, Jamal A. Ibdah Background: In the western world, 25-30% of adults have non-alcoholic fatty liver disease (NAFLD). Of those with NAFLD, 1/3 will develop non-alcoholic steatohepatitis (NASH), which potentially can progress to cryptogenic cirrhosis and advanced liver failure. Insulin resistance (IR) is thought to be a key element of NAFLD progression. Insulin sensitizing medications (IS) are believed to be an affective method for treating NAFLD. Several random- ized controlled trials (RCTs) have been performed to evaluate the effects of medications and lifestyle modifications but the results have been inconsistent and controversial. Therefore, we conducted a meta-analysis to evaluate the role of IS in the management of NAFLD. Methods: MEDLINE, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, PubMed, and recent abstracts from major conference proceedings were searched (10/08). RCTs comparing IS at any dose and duration versus no intervention or placebo were included. Co-interventions were allowed in both groups in all the trials. Standard forms were used to extract data by two independent reviewers. The effects were analyzed by calculating pooled estimates of steatosis, hepatocellular injury, fibrosis, NAFLD activity score (NAS), ALT, IR, C-reactive protein (CRP), and leptin. Separate analyses were performed for each outcome by using odds ratio (OR) or weighted mean difference (WMD) by random or fixed effect models. Publication bias was assessed by funnel plots. Heterogeneity among studies was assessed by calculating I2 measure of inconsistency. Results: Seven trials met inclusion criteria. IS significantly decreased the odds of steatosis (OR 3.31; 95% CI: 1.63- 6.74, p<0.01), hepatocellular injury (OR 2.60; 95% CI: 1.24-5.43, p=0.01), and NAS (OR 2.88; 95% CI: 1.16-7.13, p=0.02). IS had a trend toward decreased fibrosis but not to a significant level (OR 1.65; 95% CI: 0.75-3.62, p=0.21). Also, IS significantly increased the odds of normalization (OR 3.72; 95% CI: 1.93-7.16, p<0.01) or improvement of ALT (OR 30.85; 95% CI: 19.13-42.56, p<0.01) and HOMA-IR (OR -1.15; 95% CI:-1.61- -0.69, p<0.01). However, no significant effect was noted on leptin (OR 1.48; 95% CI:-1.46- 4.43, p=0.32) and CRP serum levels (OR -1.26; 95% CI:-2.77-0.26, p=0.1). No significant heterogeneity was present for all the major outcomes. Funnel plot revealed no publication bias. Conclusion: IS significantly improves histology and biochemical markers in NAFLD/ NASH in comparison to placebo or no interventions. T1009 Severity of Liver Injury and Cardiovascular Risk in Children with Nonalcoholic Fatty Liver Disease Valerio Nobili, Naim Alkhouri, Anna Alisi, Melania Manco, Andrea Bartuli, Rocio Lopez, Ariel E. Feldstein Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and is tightly associated with obesity and insulin resistance (IR). NAFLD encompasses a wide spectrum of disease ranging from simple fatty liver to steatohepatitis (NASH), a serious condition that may progress to end stage liver disease. A number of studies have suggested a link between NAFLD and cardiovascular disease. However, the association between severity of NAFLD and cardiovascular (CV) risk remains poorly under- stood in adults and completely unknown in children. Thus, the aim of this study was to assess the relationship between severity of liver injury and cardiovascular risk markers in a large, well-characterized group of children with NAFLD. Methods: A total of 118 children with biopsy-proven NAFLD were included. Histology was assessed by an experienced patho- logist and the NAFLD activity score (NAS) and fibrosis score were calculated for each patient. Anthropometrics, blood pressure, and metabolic profile including fasting glucose, insulin, glucose tolerance test, and lipid panels were done in all patients. Metabolic Syndrome (MS) was defined according to the International Diabetes Federation criteria for children and adolescents. IR was determined using the homeostatic model assessment (HOMA). CV risk markers included: triglyceride (TG)/HDL, total cholesterol/HDL, LDL/HDL, and ApoB/ApoA- 1 ratios. Results: The NAS and fibrosis score showed a significant positive correlation with TG /HDL, total cholesterol/HDL, and LDL/HDL ratios (p < 0.001 for all), but not with ApoB/ ApoA-1 ratio (p = 0.58). After adjusting for BMI, HOMA, impaired glucose tolerance, and presence of MS, both NAS and stage of fibrosis remained independent predictors of higher lipid ratios. Finally, all lipid ratios, except for ApoB/ApoA-1, were found to be markedly higher in children with established NASH compared to those with simple steatosis or borderline disease (p < 0.005 for all). Conclusions: Our study demonstrates for the first time that in children with NAFLD, the severity of liver injury is strongly associated with the presence of a more atherogenic lipid profile. These results suggest a significant relationship between the severity of NAFLD and increased CV risk in children and have potential significant diagnostic and therapeutic implications. T1010 Mass Spectrometry-Based Serum Proteomics Approach to Biomarker Discovery for Non-Invasive Diagnostics of Non-Alcoholic Steatohepatitis (NASH) Janice L. Theodorakis, Raj Vuppalanchi, Jinsam You, Kerry G. Bemis, Shawn C. Comella, Naga P. Chalasani The incidences of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rising concurrently with obesity, metabolic syndrome, and cardiovascular disease. Although simple steatosis is largely benign, NASH is progressive with risk of developing cirrhosis and liver failure. The purpose of this study, utilizing a non-biased proteomics approach, is to identify new, non-invasive biomarkers that accurately predict the presence and stage of fibrosis. We have analyzed serum from 85 patients: 16 obese without liver disease; 24 simple steatosis; 23 NASH; and 22 NASH with advanced fibrosis. Using a label- free mass spectrometry-based protein quantification method, we identified 1738 proteins in the serum proteome, of which 605 change significantly between at least two patient groups. Changes in serum levels of individual proteins are considered significant when a AASLD Abstracts