928 Prevalence and Associations of Non-Alcoholic Fatty Liver Disease in the Elderly

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has not been elucidated. Methods: All patients in the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) Participant User File 2005-2011 were studied. When measured during the 90-day preoperative period, SGOT laboratory values were categorized as normal or elevated ( ≥40 U/L); if untested, values were unknown. MACE identifiable within the 30-day postoperative period included cerebrovascular accident, cardiac arrest requiring CPR, and myocardial infarction. Obesity was defined as a body-mass index ≥ 30. Using multivariable logistic regression, patient and operative factors associated with SGOT testing, elevated SGOT and the adjusted effects of SGOT on MACE were identified. Results: The cohort consisted of 1,777,035 surgical patients. Patient variation in SGOT testing and elevated SGOT levels were observed (Table). MACE within 30 days were experienced by 0.93% (16,516) of the cohort. After adjusting for potential confounders, elevated SGOT was associated with increased odds of MACE within 30 days (Odds Ratio vs normal SGOT = 1.35, 95% CI 1.29-1.41) Patients with SGOT untested in the ninety days before surgical intervention were at lower risk of MACE than those with normal levels (Table). SGOT had a similar effect on obese patients with no to moderate alcohol intake. Conclusions: Patients with elevated SGOT are at an increased risk of MACE in the thirty days following surgical intervention and may warrant further pre-operative cardiovascular screening.

AASLD Abstracts

Early Cardiovascular Disease Mortality After Liver Transplantation—Is Nonalcoholic Steatohepatitis (NASH) to Blame? Lisa B. VanWagner, Brittany Lapin, Donald Lloyd-Jones, Anton I. Skaro, Mary E. Rinella BACKGROUND: Nonalcoholic steatohepatitis (NASH) is independently associated with an increased risk of cardiovascular disease (CVD). However, whether this association affects perioperative liver transplant (LT) outcomes is unknown. Thus, we examined the association between NASH and early CVD mortality after LT. METHODS: A cohort of 6,932 adults with NASH or cryptogenic cirrhosis thought secondary to NASH who underwent first LT from 2/2002-12/2012 was identified using the U.S. Organ Procurement and Transplantation Network (OPTN) database. Those listed as status 1 or prior to MELD inception were excluded. Recipient cause of death was manually reviewed and a physician panel adjudicated cases. Logistic regression models examined associations between NASH and early (30day) CVD mortality, defined as primary cause of death from arterial/pulmonary embolism, arrhythmia, heart failure, myocardial infarction, cardiac arrest and/or stroke. Kaplan-Meier analysis assessed survival. RESULTS: NASH patients were older (57.4 vs. 52.9 years), more likely to be female (43.3% vs. 30.9%), obese (BMI ≥ 30 mg/kg2, 51.8% vs. 30.5%), and have diabetes (46.2% vs. 21.1%) compared to non-NASH (p<0.001). Although there was no significant difference in long-term all-cause mortality (log-rank, p=0.714), early all-cause mortality was increased in NASH compared to non-NASH (3.4% vs. 2.6%, p=0.03). Of 235 early NASH deaths, 107 (40.5%) were CVD-related. In multivariable analyses adjusted for age, sex, diabetes and BMI, NASH was associated with an increased risk of early CVD mortality (OR=1.26, 95% CI: 1.01-1.58). CONCLUSION: NASH is associated with an increased risk of early CVD-related mortality despite acceptable long-term outcomes. Future studies that address the high prevalence of cardiovascular comorbid conditions in this rapidly growing patient population are needed to potentially reduce early mortality after liver transplantation for NASH cirrhosis. 926 Automatic Quantification of Liver Histology in NAFLD: A Promising Tool to Facilitate Better Histological Characterization in NAFLD Scott Vanderbeck, Joseph Bockhorst, Richard Komorowski, David E. Kleiner, Naga P. Chalasani, Samer Gawrieh Background: Automatic quantification of cardinal histological features of non-alcoholic fatty liver disease (NAFLD) may reduce observer variability and allow continuous rather than semi-quantitative assessment of injury. We have recently developed an automated classifier able to detect and quantify macrosteatosis with high precision and sensitivity ( ≥95%). Here we report our early results on the classifier's performance in detecting lobular inflammation and hepatocellular ballooning. We assessed the correlation of these measurements with the semi-quantitative grading of two expert pathologists. Methods: Automatic quantification of steatosis, lobular inflammation and ballooning was performed on digital images obtained at 20 x magnification using the Hamamatsu NanoZoomer scanner of H&E stained slides of liver biopsy samples from 47 individuals [20 with normal liver histology, 19 with NAFL, and 8 with NASH]. Liver biopsies were read and scored by the two study pathologists according the NASH CRN scoring system. In addition, classifiers were created based on annotations of the digital images provided by the study pathologists via a web-based applet. Quantification of the three lesions was carried out using models that utilize state- of-the art supervised machine learning techniques. Evaluation of lesion classification was carried out using a 10-fold cross-validation experiment. Results: The model's precision, sensitivity and AUROC were 70%, 49% and 95% respectively for lobular inflammation, and 91%, 54% and 98%, respectively for ballooning. When correlated with the average of the two expert pathologists' semi-quantitative grading, the model had a Spearman rank correlation coefficient of 90.8% for steatosis, 45.2% for lobular inflammation and 46% for ballooning. The correlations achieved in all three categories represent a statistically significant improvement over the correlation coefficients for the pathologist to pathologist agreements which were 84.3%, -1.4%, and 24.8% for steatosis, lobular inflammation, and ballooning, respectively. There was an overall 73.8% correlation between the NAS computed by our model and the average NAS obtained from our study pathologists (Figure 1). Conclusions: Our novel observations offer promise for further development of automatic quantification as a potential aid to pathologists evaluating NAFLD biopsies in clinical practice and clinical trials.

adjusted for sex, race, functional status, selected comorbities, smoking status, cancer status, steroid use, dialysis, selected prior health events or procedures, anesthesia type, wound status, and RBC transfusion 928 Prevalence and Associations of Non-Alcoholic Fatty Liver Disease in the Elderly Way Siow, Suzanne H. Niblett, Katrina King, Zoe R. Yates, Mark Lucock, Martin Veysey Introduction: Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of liver pathology ranging from steatosis to steatohepatitis in the absence of excessive alcohol consumption. NAFLD frequently co-exists with obesity and the metabolic syndrome with a parallel increase in the prevalence of these conditions over the last two decades. There is, however, limited data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in the elderly. The aim of this study was, therefore, to use a non-invasive method to assess the prevalence of NAFLD in an older Australian population and examine the relationships between the presence of NAFLD with other markers of metabolic syndrome and inflammation. Methods: We prospectively recruited 831 community-based participants, aged over 65 years, who completed a questionnaire assessing their medical history, including all types of liver diseases, metabolic risk factors, medications and alcohol intake. These subjects had their BMI, body anthropometry and biochemistry analysed. Fatty liver index (FLI)1 is a validated non-invasive method of estimating the likelihood of NAFLD in individuals. FLIs were calculated and subjects were classified into three categories, FLI <30 (No NAFLD), 30 ≤ FLI < 60 (Borderline) and FLI ≥ 60 (NAFLD). Results: For analysis, subjects with other liver diseases and alcohol intake >20g/day were excluded, leaving 440 individuals (mean age 78yr, 264 females). Of note, only one of the participants with FLI ≥60, and one with a borderline value, self-reported NAFLD in their medical history. Results are given as means ±SD. For the whole population, there were significant linear relationships between FLI and ALT (r=0.23, p<0.01), insulin (r=0.47, p<0.001), fasting glucose (r=0.34, p<0.001) and CRP (r=0.16, p<0.01). Conclusions: NAFLD has a high prevalence in the elderly (43.2%) and largely goes unrecognised. Mildly elevated ALT may be a useful and simple surrogate marker for the presence of non-alcoholic fatty liver disease in this population, particularly in obese individuals without excessive alcohol intake. NAFLD is also clearly associated with insulin resistance, type 2 diabetes and inflammation in the elderly. 1Koehler E et al. External Validation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in a Population-based Study. Clin Gastroenterol Hepatol. 2013; 11:1201-1204

927 The Impact of Elevated Liver Enzymes and Other Patient Characteristics on 30-Day Post-Operative Major Adverse Cardiac Events: An ACS-NSQIP Analysis Julie Heimbach, John Stulak, Amy Wagie, Sharon Nehring, Martin D. Zielinski, Karla Ballman, Elizabeth B. Habermann Background: Though elevated liver enzymes have been associated with increased risk of cardiovascular disease in the general population, the effect of elevated serum glutamicoxaloacetic transaminase (SGOT) on Major Adverse Cardiac Events (MACE) following surgery

AASLD Abstracts

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survival and increased risk of hospitalization and OHE development despite controlling for MELD score. Strategies to treat CHE may improve these risks. Covert HE and Development of Outcomes

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Background: Malnutrition is a frequent complication of cirrhosis, and it has been associated with a more severe disease. There is no gold standard for nutritional assessment in cirrhosis, and intrinsic pathophysiologic changes make biochemical markers and traditional methods used to evaluate malnutrition unreliable. Phase angle (PhA) obtained from bioelectrical impedance has been successfully used as a nutritional marker in diseases such as chronic renal failure, cancer, and HIV. In cirrhosis, research linking malnutrition to increased mortality has yielded conflicting results. Recently, a few PhA cut-off points have been proposed to define malnutrition in cirrhosis, and found to be useful in predicting severe disease and mortality. Since evidence is still limited and PhA needs specific validation in different ethnic groups, we aimed to evaluate the PhA cut-off value that would best define malnutrition and predict mortality in Mexican patients with cirrhosis. Materials and methods: Prospective cohort study with mean follow-up of 34±14 months. Clinical (presence of esophageal varices, ascites, edema, and hepatic encephalopathy), nutritional (bioelectrical impedance) and biochemical evaluations were performed. ANOVA, t-test or X2 were used as appropriate. PhA cut-off value was established using area under ROC curve. KaplanMeier curves and log-rank test were used to evaluate mortality, followed by multivariate Cox regression. Results: 249 patients (60% females), with mean age 52±11 years, were included. Most frequent etiology of cirrhosis was hepatitis C infection (36%). There were no significant differences between genders except for a higher weight in males (79± 16 vs 63±14 kg, p<0.001). ROC curve analyses yielded 5.1° as the best PhA cut-off value associating malnutrition with mortality. When we divided the population according to PhA ≤ or >5.1° there were no significant differences in demographic, clinical and biochemical variables between groups. Survival analysis showed higher mortality in the group with PhA ≤5.1° compared to the group with PhA >5.1° (p=0.02) (Figure 1). Child-Pugh, MELD score, total bilirubin, and albumin were associated with higher mortality as well. In the multivariate analysis controlling for relevant demographic, biochemical parameters, and cirrhosis complications only MELD score (HR=1.51,1.20-4.30), grade 3 ascites (HR=2.04, 1.10-6.76), and PhA ≤5.1° (HR=2.13, 1.13-4.21) remained associated with mortality. Conclusions: In our cohort of cirrhotic patients, a PhA ≤ 5.1° from bioelectrical impedance was independently associated with mortality. This cut-off value is different from others previously reported. In conclusion, a PhA ≤ 5.1°can be used as reference in Mexican patients to identify malnutrition associated with an unfavorable prognosis, in order to establish timely nutritional therapy.

Associations of Sleep Duration and Sleep Quality With Clinical and Histologic Features of Nonalcoholic Fatty Liver Disease (NAFLD) Sweta Kochhar, Manal F. Abdelmalek, Cynthia D. Guy, Dawn Piercy, Yiping Pan, Anna Mae Diehl, Ayako Suzuki Background & Aim: Sleep deprivation and poor quality sleep are associated with various metabolic derangements. A recent study revealed that sleep deprivation increases a risk of NAFLD. In this study, we aimed to assess whether sleep deprivation and poor quality sleep are associated with clinical and histologic features of NAFLD. Methods: We analyzed 689 adult patients with clinical diagnosis of NAFLD who were enrolled in the Duke NAFLD Clinical Database study and had liver biopsy. Information on demography, body mass index (BMI), co-morbidity, laboratory data, current sleep duration and sleep difficulty was collected at the time of biopsy. Liver biopsies were scored for steatosis, lobular inflammation, ballooning, portal inflammation, and fibrosis according to the NASH CRN scoring system. Sleep deprivation was defined as self-reported sleep less than 7 hours per day, while sleep difficulty was defined by either physician's diagnosis or answering yes to at least one of the 4 screening questions for sleep difficulty. Sleep apnea was defined by physician's diagnosis. Sleep duration, sleep difficulty and sleep apnea were then associated with BMI, serum uric acid, presence of diabetes or glucose intolerance (DM/GI), hypertension (HTN), and hyperlipidemia (HL), and histologic grades/stage of NAFLD using Chi-square tests, ANOVA, and multiple linear (logistic) regression models. Results: Average and SD of age and BMI were 48±11 years and 40±10 kg/m2 in this population. 33% were men, 83% Caucasian. 82% had histologic diagnosis of NAFLD while the rest had minimal histologic findings. 22% had advanced fibrosis. Sleep deprivation, sleep difficulty, and sleep apnea were noted in 35.5%, 67%, and 41% of the population. After adjusting for age, gender, and other sleep conditions, sleep deprivation was associated with a higher serum uric acid (p<0.05) and a decreased risk of having more severe lobular inflammation (cumulative odds ratio or COR[95% CI] = 0.5[0.3, 0.7], p=0.0007). Sleep difficulty, on the other hand, tended to be associated with an increased risk of having more severe steatosis (COR[95% CI] = 1.3[1.0, 1.8], p=0.07). Sleep apnea was also associated with an increased BMI (p<0.0001), an increased risk of DM/IG (OR[95% CI] = 1.7[1.2, 2.4], p=0.0066), HTN (OR[95% CI] = 1.3[1.0, 1.8], p=0.006), and steatosis(COR with 95% CI = 1.6[1.2,2.1], p=0.003), and tended to be associated with an increased risk of HL(OR[95% CI] = 1.4[1.0,2.1], p=0.08) and fibrosis (COR with 95% CI = 1.3[1.0,1.8], p=0.06). Conclusions: Independent of sleep apnea, sleep deprivation was associated with a higher serum uric acid and a decreased risk of lobular inflammation while sleep difficulty showed a tendency toward an increased risk of steatosis. The findings suggest that sleep duration and quality may impact metabolic and histologic features among patients with NAFLD. 989 Covert Hepatic Encephalopathy Is Independently Associated With Poor Survival and Increased Risk of Hospitalization: A Prospective Study of 170 Patients Kavish R. Patidar, Leroy R. Thacker, Melanie B. White, James B. Wade, Richard K. Sterling, Arun J. Sanyal, R. Todd Stravitz, Velimir A. Luketic, Michael Fuchs, HoChong Gilles, Douglas M. Heuman, Jasmohan S. Bajaj Background: Covert HE (CHE) is prevalent in cirrhosis but its natural history, especially its independent role in predicting survival and hospitalization is unclear. Aim: To define the impact of CHE on development of overt HE(OHE), hospitalization, death and transplant in a large prospectively followed cirrhotic population. Methods: Outpatient cirrhotics without OHE or neuropsychiatric issues were enrolled and were administered a standard paperpencil cognitive battery for CHE diagnosis validated in our center. All patients were followed and time for first OHE development. hospitalization and transplant/death were compared between CHE/no-CHE patients using Cox regression. Results: 170 cirrhotic patients (55 yrs, 59% men, 14 yrs education, MELD 10, 45% HCV, 20% alcoholic etiology) were included, of whom 57% had CHE. Patients were followed up a median of 55.5 months during which 30% first developed OHE at a median of 8.5 months (2.0,18.0 months IQR) after the initial visit, 42% were first hospitalized a median of 10 months(3.0, 26.0 months IQR) later,13% died a median of 21.5 months (10.0, 34.0 months IQR), and 19% had a composite death/ transplant outcome a median of 25 months(10.0, 34.0 months,IQR) after the initial visit. Age, gender, alcoholic etiology, MELD score and CHE status were included in Cox-regression models for times to first OHE episode, first hospitalization, death and composite death/ transplant outcomes. On Cox-regression, despite controlling for MELD, those with CHE at baseline had twice the risk of developing OHE,two and half times the risk of hospitalization, five times the risk of dying and three times the risk of getting transplanted or dying in the follow-up period (table). Apart from MELD and CHE, none of the other included variables were significant in predicting outcomes. Conclusions: Covert HE is associated with worsened

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AASLD Abstracts

AASLD Abstracts

Phase Angle As a Nutritional Marker Related to Prognosis in Patients With Liver Cirrhosis: A Cut-off Value for Mexican Population Astrid Ruiz-Margáin, Ricardo U. Macias-Rodriguez, Silvia L. Rios-Torres, Angeles Espinosa-Cuevas, Andres Duarte-Rojo, Aldo Torre