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Early Cardiovascular Disease Mortality After Liver Transplantation—IsNonalcoholic 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 anincreased risk of cardiovascular disease (CVD). However, whether this association affectsperioperative liver transplant (LT) outcomes is unknown. Thus, we examined the associationbetween NASH and early CVD mortality after LT. METHODS: A cohort of 6,932 adultswith NASH or cryptogenic cirrhosis thought secondary to NASH who underwent first LTfrom 2/2002-12/2012 was identified using the U.S. Organ Procurement and TransplantationNetwork (OPTN) database. Those listed as status 1 or prior to MELD inception wereexcluded. Recipient cause of death was manually reviewed and a physician panel adjudicatedcases. Logistic regression models examined associations between NASH and early (30-day) CVD mortality, defined as primary cause of death from arterial/pulmonary embolism,arrhythmia, heart failure, myocardial infarction, cardiac arrest and/or stroke. Kaplan-Meieranalysis assessed survival. RESULTS: NASH patients were older (57.4 vs. 52.9 years), morelikely to be female (43.3% vs. 30.9%), obese (BMI ≥ 30 mg/kg2, 51.8% vs. 30.5%), andhave diabetes (46.2% vs. 21.1%) compared to non-NASH (p<0.001). Although there wasno significant difference in long-term all-cause mortality (log-rank, p=0.714), early all-causemortality was increased in NASH compared to non-NASH (3.4% vs. 2.6%, p=0.03). Of 235early NASH deaths, 107 (40.5%) were CVD-related. In multivariable analyses adjusted forage, sex, diabetes and BMI, NASH was associated with an increased risk of early CVDmortality (OR=1.26, 95% CI: 1.01-1.58). CONCLUSION: NASH is associated with anincreased risk of early CVD-related mortality despite acceptable long-term outcomes. Futurestudies that address the high prevalence of cardiovascular comorbid conditions in this rapidlygrowing patient population are needed to potentially reduce early mortality after livertransplantation for NASH cirrhosis.

926

Automatic Quantification of Liver Histology in NAFLD: A Promising Tool toFacilitate Better Histological Characterization in NAFLDScott Vanderbeck, Joseph Bockhorst, Richard Komorowski, David E. Kleiner, Naga P.Chalasani, Samer Gawrieh

Background: Automatic quantification of cardinal histological features of non-alcoholic fattyliver disease (NAFLD) may reduce observer variability and allow continuous rather thansemi-quantitative assessment of injury. We have recently developed an automated classifierable to detect and quantify macrosteatosis with high precision and sensitivity ( ≥95%). Herewe report our early results on the classifier's performance in detecting lobular inflammationand hepatocellular ballooning. We assessed the correlation of these measurements with thesemi-quantitative grading of two expert pathologists. Methods: Automatic quantification ofsteatosis, lobular inflammation and ballooning was performed on digital images obtained at20 x magnification using the Hamamatsu NanoZoomer scanner of H&E stained slides ofliver 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 pathologistsaccording the NASH CRN scoring system. In addition, classifiers were created based onannotations 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 artsupervised machine learning techniques. Evaluation of lesion classification was carried outusing a 10-fold cross-validation experiment. Results: The model's precision, sensitivity andAUROC 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 expertpathologists' semi-quantitative grading, the model had a Spearman rank correlation coefficientof 90.8% for steatosis, 45.2% for lobular inflammation and 46% for ballooning. The correla-tions achieved in all three categories represent a statistically significant improvement overthe correlation coefficients for the pathologist to pathologist agreements which were 84.3%,-1.4%, and 24.8% for steatosis, lobular inflammation, and ballooning, respectively. Therewas an overall 73.8% correlation between the NAS computed by our model and the averageNAS obtained from our study pathologists (Figure 1). Conclusions: Our novel observationsoffer promise for further development of automatic quantification as a potential aid topathologists evaluating NAFLD biopsies in clinical practice and clinical trials.

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The Impact of Elevated Liver Enzymes and Other Patient Characteristics on30-Day Post-Operative Major Adverse Cardiac Events: An ACS-NSQIPAnalysisJulie Heimbach, John Stulak, Amy Wagie, Sharon Nehring, Martin D. Zielinski, KarlaBallman, Elizabeth B. Habermann

Background: Though elevated liver enzymes have been associated with increased risk ofcardiovascular disease in the general population, the effect of elevated serum glutamic-oxaloacetic transaminase (SGOT) on Major Adverse Cardiac Events (MACE) following surgery

S-930AASLD Abstracts

has not been elucidated. Methods: All patients in the American College of Surgeons' NationalSurgical Quality Improvement Program (ACS-NSQIP) Participant User File 2005-2011 werestudied. When measured during the 90-day preoperative period, SGOT laboratory valueswere categorized as normal or elevated (≥40 U/L); if untested, values were unknown. MACEidentifiable within the 30-day postoperative period included cerebrovascular accident, cardiacarrest requiring CPR, and myocardial infarction. Obesity was defined as a body-mass index≥ 30. Using multivariable logistic regression, patient and operative factors associated withSGOT 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 testingand elevated SGOT levels were observed (Table). MACE within 30 days were experienced by0.93% (16,516) of the cohort. After adjusting for potential confounders, elevated SGOTwas 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 surgicalintervention were at lower risk of MACE than those with normal levels (Table). SGOT hada similar effect on obese patients with no to moderate alcohol intake. Conclusions: Patientswith elevated SGOT are at an increased risk of MACE in the thirty days following surgicalintervention and may warrant further pre-operative cardiovascular screening.

adjusted for sex, race, functional status, selected comorbities, smoking status, cancer status,steroid use, dialysis, selected prior health events or procedures, anesthesia type, woundstatus, and RBC transfusion

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Prevalence and Associations of Non-Alcoholic Fatty Liver Disease in theElderlyWay Siow, Suzanne H. Niblett, Katrina King, Zoe R. Yates, Mark Lucock, Martin Veysey

Introduction: Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum ofliver pathology ranging from steatosis to steatohepatitis in the absence of excessive alcoholconsumption. NAFLD frequently co-exists with obesity and the metabolic syndrome witha 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 theelderly. The aim of this study was, therefore, to use a non-invasive method to assess theprevalence of NAFLD in an older Australian population and examine the relationshipsbetween 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 liverdiseases, metabolic risk factors, medications and alcohol intake. These subjects had theirBMI, body anthropometry and biochemistry analysed. Fatty liver index (FLI)1 is a validatednon-invasive method of estimating the likelihood of NAFLD in individuals. FLIs werecalculated and subjects were classified into three categories, FLI <30 (No NAFLD), 30 ≤FLI < 60 (Borderline) and FLI ≥ 60 (NAFLD). Results: For analysis, subjects with otherliver diseases and alcohol intake >20g/day were excluded, leaving 440 individuals (meanage 78yr, 264 females). Of note, only one of the participants with FLI ≥60, and one witha 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 andALT (r=0.23, p<0.01), insulin (r=0.47, p<0.001), fasting glucose (r=0.34, p<0.001) andCRP (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 surrogatemarker for the presence of non-alcoholic fatty liver disease in this population, particularlyin obese individuals without excessive alcohol intake. NAFLD is also clearly associated withinsulin resistance, type 2 diabetes and inflammation in the elderly. 1Koehler E et al. ExternalValidation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in aPopulation-based Study. Clin Gastroenterol Hepatol. 2013; 11:1201-1204