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BMI; body mass index, DM; diabetes,

Tu1923

Components of Metabolic Syndrome and the Rising Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis(NASH) in the United StatesMaria Stepanova, Mariam Afendy, Gregory C. Vernon, Fatema Nader, Zobair M. Younossi

The recent epidemic of obesity and other components of metabolic syndrome are expectedto contribute to the prevalence of NAFLD and NASH in the United States. METHODS: Inthis study, we used two cycles of the National Health and Nutrition Examination Survey(NHANES) which were conducted approximately 20 years apart (1988-1994 and 2005-2008). For the purpose of this study, diagnoses of NAFLD was established as abnormalALT and AST (ALT >40 U/L, AST >37 U/L in men and ALT, AST >31 U/L in women.) inthe absence of all other types of chronic liver diseases (HCV antibody and HCV RNA negative,HBV surface antigen negative, normal transferrin saturation and alcohol consumption lessthan 10 grams per day in women or <20g/day in men). For the purpose of this study, NASHwas defined as individuals without any evidence for chronic liver disease other than elevatedaminotransferases (defined as above) who also had type 2 diabetes. This definition wasbased on extremely high prevalence of NASH in patients with DM and elevated liver enzymes.Logistic regression was used to identify independent predictors of both NAFLD and NASH.Statistical analyses were performed using SUDAAN 10.0 (SAS Institute, Cary, NC).RESULTS:In this study, a total of 25,536 adults were included from two NHANES cycles (1988-1994,N=15,866 and 2005-2008, N=9,670). Over this period of time, the prevalence of NAFLDdoubled from the initial rate of 5.51±0.31% (1988-1994) to 11.01±0.51% (2005-2008)(p<0.0001). During the same period of time, the prevalence of NASH also doubled from0.65±0.07% (1988-1994) to 1.10±0.14% (2005-2008) (p=0.0055). Furthermore, the preval-ence of obesity (defined as BMI>30) raised from 21.74±0.65% to 33.22±1.08% (p<0.0001),as well as the prevalence of visceral obesity (defined using ATP-III threshold) [35.2±0.5%to 51.4±1.3%, p<0.0001], type 2 diabetes (DM) [5.55±0.29% to 9.11±0.47%, p<0.0001],insulin resistance (defined as HOMA>3.0) [23.29± 0.80% to 35.00±1.41%, p<0.0001] andhypertension [22.68±0.80% to 34.08±1.05%, p<0.0001]. In the multivariate analysis, obesityand DM remained independent predictors of NAFLD and NASH over the past two decades.If the current increases in rate of obesity and DM continue, the prevalence of NAFLD andNASH in the United States is expected to increase by at least 50% over the next two decades.CONCLUSIONS: In parallel to the increase in the prevalence of components of metabolicsyndrome, the prevalence of NAFLD and NASH are steadily rising in the United States. Thisincrease will probably make NAFLD/NASH the most important future cause of liver diseasecontributing significantly to the burden of chronic diseases in the United States.

Tu1924

Type 2 Diabetes Increases the Mortality Among Patients With Non AlcoholicFatty Liver DiseaseSombat Treeprasertsuk, Felicity Enders, Keith D. Lindor

BACKGROUND: Type2 diabetes has been demonstrated to be one of important risk factorsfor advanced liver fibrosis in patients with non alcoholic fatty liver disease (NAFLD). However,there is limited information of long-term outcomes for the effect of type 2 diabetes (T2DM)on the mortality rate of patients with NAFLD. We aimed to compare the mortality ratebetween NAFLD patients with and without T2DM. METHODS: We identified and analyzedthe existing data from a cohort study of 479 NAFLD patients diagnosed during 1980 and2000 drawn from the Rochester Epidemiology Project. We excluded 177 patients due toincomplete data, known coronary heart disease (CHD) or known liver complications. Theremaining 302 NAFLD patients with mean age of 47.3±12.9 years were followed-up for anaverage of 11.9 ± 3.9 years. Survival analysis were used to estimate the association ofmortality and T2DM. RESULTS: T2DM was present in 48 patients (16%) at the time ofNAFLD diagnosis. By univariate analysis, NAFLD patients with T2DM were older, had morefemale, more patients with hypertension, more patients with higher liver fibrosis score, highertriglyceride and glucose levels, and more patients with higher AST and ALT ratio(p<0.05). Atthe end of follow up 39 patients (12.9%) died. Of 246 NAFLD patients without T2DM atbaseline, 86 of them (34%) developed diabetes during the follow-up. NAFLD patients withT2DM had significantly higher mortality rate than those without T2DM (23% vs. 11%).Survival analysis showed that NAFLD patients with T2DM had a significantly higher mortalityrate then those without T2DM ((log-rank test statistics =35.5 ; P= 0.003; figure1). CONCLU-SIONS: Type 2 diabetes is associated with a higher mortality rate among those patientswith NAFLD.Clinical parameters, laboratory features at baseline of NAFLD patients grouped by statusof T2DM.

S-988AASLD Abstracts

NAFLD with or without T2DM and mortality

Tu1925

Validity of the Non-Alcoholic Fatty Liver Disease Activity Score (NAS):Comparing the Nas With Pathology DiagnosisMichael Hjelkrem, Chris Stauch, Stephen Harrison, Janet Shaw

PURPOSE: The NAS is a scoring system, developed by the Nonalcoholic Steatohepatitis(NASH) Clinical Research Network, used to evaluate histological changes in research trialsinvolving a therapeutic intervention, in order to provide a method to compare disease activitybetween patients. However, the NAS had not been validated outside of the NASH ClinicalResearch Network. METHODS: This study retrospectively examined adult patients from atertiary medical center hepatology clinic undergoing liver biopsy to evaluate suspectedNAFLD or NASH from January 2003 to May 2010. Patients with a diagnosis of liver diseaseother than NAFLD or NASH were excluded. The biopsy specimens were evaluated twice ina blinded manner by a single expert hepatopathologist, one time to determine a biopsydiagnosis (NASH, Steatosis, or normal) and separate, second time to determine the NAS.RESULTS: Three-hundred and Eighty-six biopsy specimens were analyzed. Area under theReceiver Operating Characteristic (ROC) curve was 0.900 (P < 0.001) (excellent agreement).A diagnosis of NASH was determined in 50.8% of the biopsies, steatosis in 43.5%, andindeterminate in 5.7%. For a NAS ≥ 5 as a diagnosis of NASH and a NAS <5 for not NASHthe sensitivity was 57.1% and the specificity was 95.3% with negative predictive value (NPV)of 68.3% and positive predictive value (PPV) of 92.6%. Lowering the NAS to ≥ 4 as adiagnosis of NASH and < 4 as not NASH increased the sensitivity to 85.2% with a decreasein specificity to 80.5%, with NPV of 84.0% and PPV of 81.9%. CONCLUSION: The NASis a valid scoring system with an excellent level of agreement between the histologic diagnosisand the NAS. An NAS ≥ 4 has optimal balance between sensitivity and specificity for adiagnosis of NASH.

Tu1926

Characterization of Nonalcoholic Fatty Liver Disease Unrelated to theMetabolic SyndromeYusuf Yilmaz, Ebubekir Senates, Talat Ayyildiz, Yasar Colak, Ilyas Tuncer, Ayse O. KurdasOvunc, Enver Dolar, Cem Kalayci

Nonalcoholic fatty liver disease (NAFLD) is currently considered as the hepatic manifestationof the metabolic syndrome (MS). However, not all patients with MS will develop NAFLDand not all patients with NAFLD have MS. The aim of this multicenter cross-sectional studywas to determine the differences between patients with biopsy-proven NAFLD with andwithout a diagnosis of the MS. Our hypothesis was that a detailed characterization ofNAFLD patients who do not meet the criteria for the MS would shed more light on thepathophysiological relevance of novel mechanisms related to liver fat accumulation. Weenrolled 357 consecutive patients with biopsy-proven NAFLD (190 males and 167 females;mean age: 45.6 ± 10.2 years). The MS was defined as ≥3 of the ATP-III criteria. Twoseparate logistic regression analyses were constructed to assess the variables independentlyassociated with the presence of NASH and the presence of advanced fibrosis (≥2). A totalof 214 patients (59.9%) met the criteria for the MS, while the remaining 143 (40.1%) did