R protocol. The duration of ischemia was 90 minutes, followed by 15 minutes of reperfusion.Hepatic function was determined by quantitating serum alanine aminotransferase (ALT) andaspartate aminotransferase (AST) and by assessing mitochondrial function by the determina-tion of states 3 and 4 of mitochondrial respiration, respiratory control ratio (RCR) andthe transition of mitochondrial permeability (mitochondrial swelling). Data were analyzedstatistically by the Mann-Whitney test, with the level of significance set at p <0.05. RESULTS:There was a significant reduction of the production of mitochondrial energy (state 3 andRCR) (I/R <Sham, p<0.05) and an increase of mitochondrial edema in the I/R group withthe use of HBO (I/R=HBOI/R<Sham). Hepatic enzyme concentrations were significantlyhigher in the I/R and HBOI/R groups. CONCLUSION: The use of HBO before I/R did notimprove the production of hepatocellular energy reduced by I/R, nor did it prevent theinstallation of mitochondrial edema induced by I/R.

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Outcomes of Liver Transplantation in the United States: What Has ChangedOver the Last 25 Years?Maria Stepanova, Sharon L. Hunt, Sammy Saab, Spencer Frost, Thomas Jeffers, Zobair M.Younossi

BACKGROUND: Liver transplantation (LT) is a life-saving procedure for end-stage liverdisease. In the last 2 decades, a number of major advances in transplant procedure, immuno-suppressive regimens and candidate selection have occurred. AIM: To assess recent changesin clinical and demographic profile of liver transplant recipients and transplant outcomesin the Unites States from 1987 to 2013. METHODS: We used The Scientific Registry ofTransplant Recipients that included information about all liver transplants performed in theU.S. since 1987. Four study cycles were introduced: cycle I (1987-1993), cycle II (1994-2000), cycle III (2001-2006), cycle IV (2007-2013). Extensive pre-transplant clinical, follow-up and mortality (Social Security Death Master File) data were available. RESULTS: A totalof 95,637 adults (18+) were discharged alive after receiving LT between 1987 and June,2013. The number of LT steadily increased over time (Table 1). Over the study span, theproportion of Caucasian LT recipients decreased (83.3% in cycle I to 71.5% in cycle IV)accompanied by an increase in the proportion of non-white ethnic groups (Table 1, allp<0001). LT recipients became older, predominantly male and are now more likely to becovered by public insurance (Medicare, Medicaid, government-sponsored) (all p<0.0001).Increasingly, the indication for LT became hepatitis C which replaced alcoholic liver disease(ALD) as the primary etiology for LT (p<0.0001). Hepatitis B and ALD as the etiology forLT decreased while primary liver malignancy increased 6-fold, and NASH substantiallyincreased to 7.8% of liver transplants in 2007-2013 (p<0.0001). LT recipients becameincreasingly more overweight (BMI 25-30; from 47.6% to 67.5%) and obese (BMI>30; from17.5% to 32.9%) (both p<0.0001). Furthermore, there was an increase in type 2 diabetes(from 0% to 20.2%), hypertension (from 11.6% to 26.7%) and cardiovascular disease(1.33% to 3.94%) (all p<0.0001). Two or more metabolic disorders (diabetes, hypertension,overweight) were observed in only 4.1% of LTs in cycle I and 30.0% of LTs in cycle IV(p<0.0001). In follow-up (median (IQR)=72 (29-130) months), 35.30% recipients died and9.78% had a graft failure. The 1-, 3- and 5-year mortality rates were 6.6-7.9%, 14.9-16.8%and 21.6-23.3%, respectively. (Table 1). On the contrary, the rates of graft failure constantlydecreased with an approximately 2-fold decrease from cycle I to cycle IV in 1 year graftsurvival, and a 1.7-fold in 5-year survival (p<0.0001). CONCLUSIONS: Clinico-demographicprofile of liver transplant recipients in the U.S. is changing. The outcome of LT is improving.There are more minorities receiving LT. Given the epidemic of obesity, more LT candidateswith metabolic syndrome comorbidities and minorities are now being transplanted.Table 1. Liver transplants in the United States between 1987-2013

S-939 AASLD Abstracts

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Natural History of Inflammatory Bowel Disease Post Liver Transplantation forPrimary Sclerosing CholangitisShiva K. Ratuapli, Jonathan A. Leighton, Shabana F. Pasha, David D. Douglas, SuryakanthGurudu, Russell I. Heigh, Bashar Aqel

Background: Liver transplantation is the main treatment for patients with primary sclerosingcholangitis (PSC) and other autoimmune liver diseases, who develop advanced liver disease.Inflammatory bowel disease (IBD) occurs concomitantly in 70-80% of PSC patients. Theeffect of liver transplantation and subsequent immunosuppression on the activity of IBD isnot entirely clear, and studies have yielded conflicting results. Aims: The primary aim wasto assess the change in activity of IBD in patients undergoing liver transplantation for PSC.The secondary aim was to compare the clinical characteristics of patients with worsenedactivity of their IBD with those who had stable activity of IBD after liver transplantation.Methods: All patients who underwent liver transplantation for advanced PSC betweenDecember 2001 and July 2012, and had IBD were included in the study. Bowel symptoms,physician's global assessment and endoscopic features were used to grade the activity ofIBD into: inactive disease, mild-moderate disease, or severe disease. The activity of IBDbefore the transplant was compared to the IBD activity after transplant, and the patientswere categorized into two groups: Stable disease, Worsened disease. Demographic, clinicaland endoscopic characteristics were compared between the two groups using general linearmodels using JMP v 9.0.1 (Cary, NC). Results: A total of 30 patients (20 men) with mean(SD) age of 52 ± 13 years were included in the study. Liver disease due to PSC was theindication for transplantation in all the patients. 28 patients had ulcerative colitis and 2 hadCrohn's disease. Liver transplantation was performed after a mean (SD) duration of 13 ±12 years of IBD diagnosis, and the mean post-transplant period of IBD assessment was 6 ±4 years. IBD was inactive in 18 (60%) patients and mild- moderate in 12 (40%) patientsprior to liver transplantation. After liver transplantation, IBD activity worsened to severedisease in 10 (33%), while it remained stable in 19(63%) (Inactive disease=18, mild disease =1) and improved in 1patient. Four patients had colectomy for worsened IBD activity afterliver transplantation. Younger age and use of prednisone in combination with tacrolimuswere significantly associated (p<0.01) with worsening of IBD activity (table). Conclusion:In our study, one third of the patients had worsening of IBD activity after liver transplantation,four of whom required colectomy. The type of immunosuppression used (i.e., tacrolimusin combination with steroids) may affect the activity of IBD after liver transplantation. Furtherstudies are necessary to understand and identify the predictors of increased IBD activityafter liver transplantation.Comparison of demographic and clinical characteristics between the two groups

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Liver Transplantation for Hepatocellular Carcinoma Outside of Both Milanand UCSF Criteria: Does Etiology of Liver Disease Impact Outcomes?William C. Palmer, Justin H. Nguyen, Barry Rosser, Andrew Keaveny, Tushar Patel,Ricardo Paz-Fumagalli, Raouf Nakhleh, Denise M. Harnois

Background: Liver transplantation (LT) is the optimal treatment for selected patients withhepatocellular carcinoma (HCC). Survival of >80% at 4 years has been demonstrated forpatients with HCC meeting Milan criteria. The UCSF group reported acceptable outcomesusing a specific protocol for patients beyond Milan criteria. Proceeding with LT for HCCoutside UCSF criteria is very controversial given the concern for recurrent HCC affecting long-term outcomes. Underlying viral disease may influence post-transplant immunosuppression.However, the impact of a viral etiology on patients with HCC at higher risk of recurrenceis unknown. We sought to examine the impact of underlying etiology of liver disease onrecurrence and outcomes in patients who had explants with HCC beyond Milan and UCSFcriteria. Methods: We reviewed 87 patients after LT for HCC from 1998-2009 with explanttumor beyond Milan UCSF criteria. We compared outcomes of patients with cirrhosis dueto chronic hepatitis B or C to those from non-viral etiology, with recurrence data up to 11/2012. Results: The viral hepatitis group (n=58) had a mean LT age of 56.7 years. HepatitisC (HCV) was present in 86%, with eleven achieving SVR after transplant and one before.Mean biological MELD and mean alfa-fetoprotein (AFP) at LT were 14.4 and 537.9ng/mL,respectively. Pre-LT locoregional therapy with transarterial chemoembolization (TACE) orradiofrequency ablation (RFA) was given in 81% and 12%, respectively. At explant, meantumor count (MTC) was 4.3, mean largest tumor size (mLTS) was 4.92cm, and 46.6% hadvascular invasion. HCC recurrence occurred in 50%, with a mean patient survival time(PST) of 3.41 years. 10 of the 12 HCV patients with SVR had HCC recurrence. Patientsurvival at 1 year (1yPS) and 3 years (3yPS) was 81% and 48%, respectfully, both lowerthan the 2005-2010 Surgical Registry of Transplant Recipient (SRTR) national averages. Thenon-viral group (n=29) had a mean LT age of 61.3 years. Mean MELD and AFP were 17.3and 1190.1ng/mL, respectively. Pre-LT TACE and RFA were performed in 85% and 7%,respectively. MTC was 4.7 and mLTS was 4.95cm. 65.5% had vascular invasion. HCCrecurrence occurred in 55.2%, with a mean PST of 3.76 years. 1yPS and 3yPS was 79%and 48%, respectively, again lower than the national averages from the 2005-2010 SRTR.Conclusion: In our cohort of patients who had HCC outside of Milan and UCSF criteriathat underwent LT, the cause of liver disease did not impact recurrence of HCC or patientsurvival. Both viral and non-viral groups had similar disease burden, AFP levels, and vascularinvasion in the explant as well as cancer recurrence rates. HCV SVR did not appear toimpact HCC recurrence. Longer term survival was less favorable for patients transplantedbeyond Milan and UCSF criteria and was lower than the national average for the sametime period.

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Prediction of Early Cardiovascular Mortality Following Liver TransplantationLisa B. VanWagner, Brittany Lapin, Josh Levitsky, Anton I. Skaro, Donald Lloyd-Jones

BACKGROUND: Historically, early mortality after liver transplantation (LT) has been dueto infection or allograft failure. It is unclear if this persists in the current era of transplantation.As the LT population ages, cardiovascular disease (CVD) prevalence is expected to riseresulting in potential excess postoperative mortality. Yet, there is currently no cardiac riskscore (CRS) specific to LT candidates available to assist in predicting CVD-related deathacross transplant centers. Thus, our aim was to 1) Describe current patterns in early (30-day) post-LT mortality and 2) Develop a LT-specific CRS for the prediction of early CVD-related mortality using a multicenter national database. METHODS: Adult recipients of afirst LT were identified from the Organ Procurement and Transplantation Network (OPTN)database between February 2002 and December 2012. Those listed as status 1 or prior toMELD inception were excluded. Recipient cause of death was manually reviewed and anindependent panel of 3 physicians was used to adjudicate case mortality. Twenty-two

S-940AASLD Abstracts

variables (significant in univariate analyses) were included in a logistic regression modelwith stepwise selection to determine a predictive model of 30-day CVD mortality, definedas a primary cause of death from arterial or pulmonary embolism, arrhythmia, heart failure,myocardial infarction, primary cardiac arrest and/or stroke. Sex and center volume wereforced into the final model. The model was internally validated using bootstrapping tech-niques. RESULTS: Of 54,697 LT recipients, 1576 (2.9%) died within 30 days. CVD-relateddeath was the leading cause of 30-day mortality, accounting for 42.1% of all deaths withan early CVD mortality rate of 1.2%. (Figure 1). Mean time to CVD death was 6.2 ± 8.2days. In multivariate analysis, 9 (6 recipient, 2 donor, 1 operative) significant predictors of30-day CVD mortality were identified: age, hospitalization status, ICU status, respiratoryfailure on a ventilator, MELD score, history of portal vein thrombosis, national organ sharing(versus local/regional), donor BMI and graft cold ischemia time (Table 1). The modelshowed moderate discrimination (c-statistic 0.66, 95% CI: 0.63-0.68, after bootstrapping).CONCLUSIONS: In the current era of liver transplantation CVD-related death is the leadingcause of early mortality. The present study provides the first prognostic model for theprediction of early CVD mortality after LT with fair model accuracy. However, inclusion ofadditional variables not currently available within the OPTN database should be consideredin order to improve model accuracy and potential clinical utility.Table 1. Multivariate predictors of 30-day cardiovascular mortality after orthotopic liver trans-plantation

Abbreviations: SD, standard deviation, CI, confidence interval; ICU, intensive care unit;BMI, body mass index

FIGURE 1: Distribution of cause of death for 1,576 adult first liver transplant recipientswho died within 30 days of liver transplantation (OPTN data 2002-2012).

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Coeliac-Like Duodenal Pathology in Orthotopic Liver Transplant Patients onMycophenolate TherapyMaura Cotter, Ahmed Abu Shanab, Raphael Merriman, Aiden McCormick, KieranSheahan

Introduction and aims: Diarrhoea following orthotopic liver transplant (OLT) is a significantclinical problem associated with mycophenolate therapy (MPA) therapy. Although its patternof inducing injury in the lower gastrointestinal tract is well known, the injury pattern inthe duodenum is less extensively documented. We aimed to study the histological patternof duodenal injury in symptomatic OLT patients on MPA therapy and compare this withpatients diagnosed with coeliac disease and normal controls. Methods: Retrospective cohortdatabase of all duodenal biopsies in patients who had OLT were analyzed in a single centreover a 19 year period. Clinical characteristics were studied which included indication ofOLT and duodenal biopsy, immunosuppressant use, anti-tTG IgA serology and outcomes.Histological specimens were reviewed by two pathologists and compared with coeliac cases