Sa1020 Hyperoxic Preconditioning in Partial Liver Ischemia

better outcomes in those admitted to ITU early in their presentation. Early ITU care is associated with better outcomes for critically ill ITU patients with MELD scores less than 20.

at p <0.05. Results: there was a significant difference in state 3 values between the SHAM and I/R groups and between the IR and IRHBO groups, in state 4 values between the SHAM and IR groups, and in mitochondrial swelling between the the SHAM and I/RHBO, SHAM and I/R and IR and IRHBO groups. Conclusion: The use of HBO after IR increased the production of hepatocellular energy and also stabilized the permeability of the mitochondriaol membrane, reducing the mitochondrial edema induced by I/R.

Sa1016

AASLD Abstracts

Lessons Learned From Excess Mortality Due to Kpc-Producing Klebsiella pneumoniae in Liver Transplant Recipients Christoph Lübbert, Arne C. Rodloff, Sven Laudi, Philipp Simon, Thilo Busch, Joachim Mössner, Michael Bartels, Udo X. Kaisers

Sa1018 Description of Two New Formulas As a Predictive Index of Mortality After Orthotopic Liver Transplantation: MELD Lactate V3 and MELD Lactate V4 Tiago Silva, Nathalia M. Cardoso, Daniela Antoniali, Anibal Basile-Filho, Enio David Mente, Orlando Castro-e-Silva

Background: Nosocomial infections in immunocompromised patients frequently originate from the Gram-negative bacterium Klebsiella pneumoniae (KP). Treatment options are considerably restricted by the emergence of carbapenem-resistant strains. Organ transplant recipients are especially at risk for peri-interventional infections by multidrug-resistant bacteria, however, only little is known on the impact of K. pneumoniae carbapenemases (KPCs) producing pathogens in this setting yet. Materials & Methods: Among 103 patients either colonized or infected with KPC-2-producing KP (KPC-2-KP) during a large hospital outbreak, we identified 9 KPC-positive patients, who had undergone orthotopic liver transplantation (LTx) between 15.09.2010 and 14.09.2011 at the Leipzig University Hospital, Germany. Presence of KPC-2-KP was confirmed by culture and molecular typing was performed using pulsed-field gel-electrophoresis (PFGE). The data from these n = 9 LTR were retrospectively compared to a matched cohort of n = 35 LTR (transplanted from 2008 to 2011) with proof of invasive infections due to carbapenem-susceptible Klebsiella spp. strains (69% KP, 31% K. oxytoca), including a high proportion of ESBL-producers (71%). All patients were followed up for 6 months after LTx. Results: 89% (8/9) of KPC-2-KP-positive LTR progressed to infection (50% pneumonia, 25% surgical site infections, 25% tertiary peritonitis), and in 56% (5/9) bloodstream infection with KPC-2-KP was confirmed. Matched comparison showed a hospital mortality rate of 78% (LTR with KPC-2-KP) compared to 34% in the remaining patients (P=0.027). Six-month survival in KPC-positive LTR (22%) was significantly lower compared to LTR with sensitive Klebsiella strains (70%), and LTR with ESBL-producing Klebsiella strains (64%) (P<0.05) (FIGURE). Conclusion: We conclude that colonization with carbapenem-resistant Enterobacteriaceae (CRE) like KPC-2-KP in LTR leads to high infection rates and excess mortality. Therefore, frequent screening for CRE in patients on LTx waiting lists appears reasonable. Although active surveillance studies have demonstrated high infection rates associated with excess mortality, colonization with CRE is so far not considered a contraindication to LTx. This position might need re-evaluation with respect to the fundamental difficulties of graft allocation due to severe organ shortage in countries like Germany. In our opinion, currently available data do not justify to consider patients with end-stage liver disease and evidence of persistent colonization by CRE failing decolonization efforts for LTx.

Introduction: The Model for End Stage Liver Disease (MELD) has been used for organ allocation and as a predictor of mortality after orthotopic liver transplantation (OLT). OLT shows survival rates of about 80%, ranging from 65 to 90% in the first 3 years and, due to the high complexity of the surgery, the mortality rates during the first 30 postoperative days range from 5 to 10%. Because of the limitations of MELD in predicting short-term postoperative complications, several studies have been conducted in order to improve it as a predictive index, although still with important limitations. Objective: To elaborate a new mathematical model for the determination of prognosis during the first 30 days after OLT and to compare two versions of the model created. Method: The study was conducted on 58 patients submitted to OLT at the University Hospital, between October 2008 and March 2012. The last 29 patients who survived and the last 29 who died within the first 30 postoperative days were selected. Lactate, INR, total bilirubin and creatinine concentrations were determined in all patients during the immediate postoperative period. Original MELD, MELD lactate V3 and MELD lactate V4 values were calculated for the study groups. Results: The models elaborated were: MELD Lactate V3 = 6.80 x loge (creatinine) + 2.42 x loge (bilirubin) + 10.3 x loge (INR) + 9.8 x loge (lactate) and MELD Lactate V4 = MELD lactate = 2.68 + 5.68 x loge (lactate) + 0.64 x (original MELD). When MELD V3 and V4 were used, statistically significant differences (P <0.05) were detected in the individual distribution of the values between survivors and non-survivors, with higher postoperative levels for the patients who died. When the ROC curves for sensitivity and specificity were compared, an AUC of 0.80 was obtained for V3, of 0.85 for V4 and of 0.69 for the original MELD. Conclusion: Both MELD lactate formulas were more efficient than the original MELD for the determination of post-OLT prognosis. The V4 version was significantly better as a predictive index of evolution during the first 30 postoperative days. Sa1019 Evaluation of DELTA (MELD, Meld Lactate V3 and MELD Lactate V4) Tiago Silva, Nathalia M. Cardoso, Daniela Antoniali, Anibal Basile-Filho, Enio David Mente, Orlando Castro-e-Silva Intruduction: The Model for End Stage Liver Disease (MELD) has been used for organ allocation and as a predictor of mortality after orthotopic liver transplantation (OLT). OLT shows survival rates of about 80%, ranging from 65 to 90% in the first 3 years and, due to the high complexity of the surgery, the mortality rates during the first 30 postoperative days range from 5 to 10%. Because of the limitations of MELD in predicting short-term postoperative complications, several studies have been conducted in order to improve it as a predictive index, although still with important limitations.In a previous study, we determined that both Meld Lactate V3 and Meld Lactate V4 proved to be sensitive as predictive indices of patient evolution after OLT. Objective: In view of the importance of the effect of hepatic ischemia in the ischemia and reperfusion phase, our objective was to determine the difference between the preoperative and postoperative results of the original Meld, Meld Lactate V3 and Meld Lactate V4. Method: The study was conducted on 78 patients submitted to OLT at between October 2008 and March 2012. The last 49 patients who survived and the last 29 who died within the first 30 postoperative days were selected. Original Meld, Meld Lactate V3 and Meld Lactate V4 values were calculated before and immediately after surgery for the two groups. At the end, we also calculated the difference between the preand postoperative values (Delta = post-pre) for the two study groups. Results: The Original Meld did not differ significantly between the patients who survived and those who died (p>0.05). Both the Meld Lactate V3 and Meld Lactate V4 showed a significant difference between the patients who survived and those who died (p<0.05). Conclusion: Both versions of the Meld Lactate formulas showed a significant difference between the Delta = post-pre values of the patients who survived and those who died 30 days after OLT. Thus, V3 and V4 are more sensitive than the Origuinal Meld for the determination of prognosis 30 days after OLT.

FIGURE: Kaplan-Meier survival curves for LTR with invasive Klebsiella spp. infections. Sixmonth survival in LTR with KPC-2-KP was significantly lower compared to LTR with sensitive Klebsiella strains (SEN Klebsiella spp., P=0.018) and patients with ESBL-producing Klebsiella strains (ESBL Klebsiella spp., P=0.005) (Cox-Mantel log rank statistics including multiple comparisons with application of the Holm-Bonferroni method). Sa1017 Effects of Hyperbaric Oxygen Therapy on the Liver After Induction of the Hepatic Ischemia/Reperfusion Complex Nathalia M. Cardoso, Daniela Antoniali, Ricardo Nejo Júnior, Leticia B. Baldim, Marina R. Silveira, Orlando Castro-e-Silva, Omar Feres

Sa1020 Hyperoxic Preconditioning in Partial Liver Ischemia Maria Rita R. Margarido, Maria Eliza Jordani de Souza, Clarice F. Fina, Maria Aparecida Neves Cardoso Picinato, Maria Cecilia Jordani Gomes, José Carlos Vanni, Orlando Castroe-Silva

Introduction: Hyperbaric oxygen (HBO) therapy is a specific type of treatment of various disorders of hypoxia using oxygen under hyperbaric conditions, increasing the quantity of oxygen dissolved in blood and in body tissues (Henry's Law) and promoting high tissue oxygen tension. Thus, the objective of the present study was to determine the effects of HBO in rats submitted to hepatic ischemia/reperfusion. Method: Twenty-three Wistar rats were divided at random into 3 groups:: SHAM, rats submitted to surgical and anesthetic stress without the induction of hepatic ischemia and reperfusion (I/R); I/R, rats submitted to total ischemia of the hepatic pedicle for 25 min followed by 5 min of reperfusion; HBOI/ R, rats submitted to 60 min of HBO therapy at the pressuure of 2 absolute atmospheres immediately after the experimental I/R protocol. Hepatic function was determined by quantitating serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and by the determination of states 3 and 4 of mitochondrial respiration, of the respiratory control ratio (RCR) and of the transition of mitochondrial permeability (mitochondrial swelling). Data were analyzed statistically by the Mann-Whitney test, with the level of significance set

AASLD Abstracts

INTRODUCTION: In ischemia-reperfusion (I/R), hepatic injury occurs due to temporary deprivation of blood flow to the liver, as observed in hepatectomies and in liver transplants. Hyperbaric oxygen (HBO) is a specific type of treatment of several hypoxia disorders consisting of the use of oxygen under hyperbaric conditions, increasing the quantity of oxygen dissolved in blood and in body tissues (Henry's Law) and promoting high tissue oxygen tension. The objective of the present study was to use HBO as hyperoxic preconditioning in rats submitted to hepatic ischemia followed by reperfusion. METHOD: Twenty-three Wistar rats were divided at random into 3 groups: SHAM, rats submitted to surgical and anesthetic stress without the induction of I/R; I/R, rats submitted to partial ischemia of 70% of the liver, with 30% of hepatic tissue being perfused; HBOI/R, rats submitted to 60 min of HBO at the pressure of 2 absolute atmospheres immediately before the experimental I/

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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) and aspartate aminotransferase (AST) and by assessing mitochondrial function by the determination of states 3 and 4 of mitochondrial respiration, respiratory control ratio (RCR) and the transition of mitochondrial permeability (mitochondrial swelling). Data were analyzed statistically 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 and RCR) (I/R
AASLD Abstracts

BACKGROUND: Liver transplantation (LT) is a life-saving procedure for end-stage liver disease. In the last 2 decades, a number of major advances in transplant procedure, immunosuppressive regimens and candidate selection have occurred. AIM: To assess recent changes in clinical and demographic profile of liver transplant recipients and transplant outcomes in the Unites States from 1987 to 2013. METHODS: We used The Scientific Registry of Transplant Recipients that included information about all liver transplants performed in the U.S. since 1987. Four study cycles were introduced: cycle I (1987-1993), cycle II (19942000), cycle III (2001-2006), cycle IV (2007-2013). Extensive pre-transplant clinical, followup and mortality (Social Security Death Master File) data were available. RESULTS: A total of 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, the proportion 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, all p<0001). LT recipients became older, predominantly male and are now more likely to be covered 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 for LT decreased while primary liver malignancy increased 6-fold, and NASH substantially increased to 7.8% of liver transplants in 2007-2013 (p<0.0001). LT recipients became increasingly more overweight (BMI 25-30; from 47.6% to 67.5%) and obese (BMI>30; from 17.5% 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 and 9.78% 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 constantly decreased with an approximately 2-fold decrease from cycle I to cycle IV in 1 year graft survival, and a 1.7-fold in 5-year survival (p<0.0001). CONCLUSIONS: Clinico-demographic profile 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 candidates with metabolic syndrome comorbidities and minorities are now being transplanted. Table 1. Liver transplants in the United States between 1987-2013

Sa1022 Natural History of Inflammatory Bowel Disease Post Liver Transplantation for Primary Sclerosing Cholangitis Shiva K. Ratuapli, Jonathan A. Leighton, Shabana F. Pasha, David D. Douglas, Suryakanth Gurudu, Russell I. Heigh, Bashar Aqel Background: Liver transplantation is the main treatment for patients with primary sclerosing cholangitis (PSC) and other autoimmune liver diseases, who develop advanced liver disease. Inflammatory bowel disease (IBD) occurs concomitantly in 70-80% of PSC patients. The effect of liver transplantation and subsequent immunosuppression on the activity of IBD is not entirely clear, and studies have yielded conflicting results. Aims: The primary aim was to 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 worsened activity of their IBD with those who had stable activity of IBD after liver transplantation. Methods: All patients who underwent liver transplantation for advanced PSC between December 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 of IBD into: inactive disease, mild-moderate disease, or severe disease. The activity of IBD before the transplant was compared to the IBD activity after transplant, and the patients were categorized into two groups: Stable disease, Worsened disease. Demographic, clinical and endoscopic characteristics were compared between the two groups using general linear models 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 the indication for transplantation in all the patients. 28 patients had ulcerative colitis and 2 had Crohn'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%) patients prior to liver transplantation. After liver transplantation, IBD activity worsened to severe disease 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 after liver transplantation. Younger age and use of prednisone in combination with tacrolimus were 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., tacrolimus in combination with steroids) may affect the activity of IBD after liver transplantation. Further studies are necessary to understand and identify the predictors of increased IBD activity after liver transplantation. Comparison of demographic and clinical characteristics between the two groups

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AASLD Abstracts