were also excluded. Differences in patient demographics and characteristics between thetwo groups were compared using independent-samples t-test. Survival analysis and thedistributions were calculated using Kaplan-Meier method and Mantel-Cox log-rank test.Results: Out of total 43 combined liver-kidney transplants, 30 SLK cases (24 post-MELDand 6 pre-MELD) were included. Proportions of age, gender, ethnicity, pre-transplant MELDscore; pre-transplant renal replacement therapy requirement, hypertension, diabetes mellitusand follow-up period were similar in two groups. Median follow up period was 30 months.Both overall and kidney-graft survival in pre-MELD era were 50%, but improved to 91.7%in post-MELD era (p=0.02). When compared according to HCV diagnosis, there was nostatistical significance in overall and kidney-graft survival between 9 HCV and 15 non-HCVgroups in post-MELD era (p=0.67 and p=0.4, respectively). Conclusion: Literature suggestslower risk of liver graft loss in SLK compared to LTA, but not much information is availableregarding the specific diagnosis of the underlying liver disease, HCV vs non-HCV.Our studydemonstrated that overall and kidney graft survival has significantly improved post-MELDas compared to pre-MELD era. Additionally, our study showed that there was no statisticaldifference in overall and kidney-graft survival between HCV and non-HCV groups. Thisobservation needs to be further studied and verified in larger cohort to fully identify theimpact of Hepatitis C infection on liver and kidney grafts, post transplantation.

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Treatment of HCV Recurrence After Liver Transplant: A Review of EarlyVirologic Responses Using Telaprevir, A Single Center Experience of 24PatientsElizabeth Cece, Guy W. Neff, Erin S. Parkinson, Nyingi Kemmer, Brenna J. Evans,Michelle Blake, Kristina Barber, Teresa Potter, Andrew Silverman, Macnish B. Christian,Christina Doligalski, Angela Logan, Annelise Nelson, Angel E. Alsina

Background: Effective antiviral therapy after liver transplant (LTx) is desperately needed toprevent graft loss and prolong post transplant survival in the chronic hepatitis C (HCV)patient population. Lack of FDA approval of direct acting antivirals (DAAs) in the post-LTxpopulation has led to a more cautious approach and therefore limited treatment experienceutilizing these agents. The purpose of this review is to report our center's early virologicresponses to triple therapy with Telaprevir (TVR) in one of the largest reported groups ofpost-transplant patients with genotype 1 recurrent HCV. Methods: Since August 2011 wehave treated 24 post-Ltx patients with genotype 1 HCV recurrence using peg-alfa 2a, ribavirin(RBV) and telaprevir (TVR). Most of these patients (17/24) were converted from tacrolimus(TAC) to cyclosporine (CyA) prior to initiation of DAA. One patient required no immunosup-pression because he received a living related donor organ. The remaining 5 patients remainedon TAC at reduced dosages at time of initiation of DAA therapy. The patients who wereconverted to CyA were admitted to the hospital prior to DAA initiation for daily monitoringof LFTs and immunosuppression (IS) levels. The remaining patients were monitored withat least weekly blood work to monitor liver function, renal function and immunosuppressionlevels. Results: There were 20 men and 4 women in the cohort who ranged from 4mos to11 years post transplant with liver pathology ranging from stage 0 to stage 4 fibrosis. Overall16/24 or 67% had early viral response achieving virus negativity by week 12. One-third ofpatients (8/24) achieved eRVR. One patient was slow to respond, not achieving viral negativityuntil week 16 but met futility with virus less than ,1000iu/mL at week 4 and 12. Sevenpatients (29%) were considered treatment failures characterized by failure to meet futilityrules, viral breakthrough, replication on therapy or early discontinuation due side effectintolerance. Two patients experienced rejection, one of whom admitted non-compliancewith treatment regimen. One death occurred due to rejection in a patient with eRVR.Conclusions: We report one of the largest experiences treating HCV recurrence post-Ltxwith TVR based triple therapy. Our population experienced vigorous early viral response.Ongoing follow-up will provide end of treatment responses and SVR data.

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Positive Lymphocyte Cross-Match Combination in Living-Donor LiverTransplantationTomohide Hori, Toshiyuki Hata, Kosuke Endo, Kanta Jobara, Shinji Uemoto

Background. There is still no consensus on the importance of lymphocyte cross-matching(LCM) in the field of living-donor liver transplantation (LDLT). Methods. LCM examinationsare routinely performed before LDLT, and the results of complement-dependent cytotoxicitywere used in this study. A total of 1157 LDLT cases were evaluated. The recipients weredivided into four groups based on the LCM and ABO compatibilities: (i) negative LCM andidentical/compatible ABO; (ii) negative LCM and incompatible ABO; (iii) positive LCM andidentical/compatible ABO; and (iv) positive LCM and incompatible ABO. The diagnosis ofantibody-mediated rejection (AMR) was made based on the clinical course, immunologicalassays and histopathological findings. C4d immunostaining was added if AMR was suspected.Results. The LCM-positive LDLT recipients showed significantly poorer outcomes than theLCM-negative recipients. Among the LCM-positive recipients, 44.1% of recipients eventuallydied and 85.2% of recipients revealed positive C4d findings. The survival rate of LCM-positive and ABO-incompatible group was 0.50. The survival days were compared withthe LCM-negative and ABO-identical/compatible group, and the LCM-positive and ABO-identical/compatible group clearly showed early death after LDLT, although the ABO-incom-patible groups did not show significant. Previous studies have documented the importantfactors for LT outcomes, such as recipient age, disease, donor age, scores of model for end-stage liver disease (MELD) or pediatric end-stage liver disease (PELD), ABO incompatibility,cold ischemic time, operative time, blood loss and graft-recipient weight ratio (GRWR). Toinvestigate which factors are important for LDLT outcomes, multivariate analyses wereperformed. The factors of age, disease, MELD/PELD scores, LCM, ABO compatibility andGRWR showed statistical significance. To investigate the effects of LCM and ABO compatibili-ties and the synergetic effects of these factors on LDLT survival, multivariate analyses wereperformed in 1121 recipients who were followed for at least 1 year and dead cases. TheLCM and ABO compatibilities each had significant effects on the LDLT survival. However,they had no synergetic effects on the LDLT survival. Conclusion. HLA antigens are more

S-955 AASLD Abstracts

widely expressed than ABO antigens, and advanced immunological strategies must be estab-lished for LCM-positive LDLT as well as for ABO-incompatible LDLT.

623

Has the Model of End Stage Liver Disease (MELD) Improved RacialDisparities in Graft Survival for Liver Transplant Recipients?Naudia L. Jonassaint, Gayane Yenokyan, L. Ebony Boulware

Background Black liver transplant recipients have poorer graft survival than white recipients.It is unclear what impact the Model of End Stage Liver Disease (MELD) has had on theseracial disparities in graft survival. Therefore, we examined racial differences in graft survivalbefore and after the institution of the MELD score. Methods The OPTN database of theUnited Network for Organ Sharing (UNOS) was used to identify recipients of deceaseddonor liver transplant in two time periods, pre-MELD (Jan 1992-Jan 2000) and post-MELD (Feb 2002-Feb 2010). Hazard of graft failure was examined in time-to-event models,sequentially adjusting for recipient demographics (age, sex), and then clinical factors (recipi-ent diagnosis) and donor demographics (age, sex and ethnicity). All analyses were limitedto black and white transplant recipients. Results There were 20291 (18,729 white, 1571black) transplant recipients pre-MELD and 28474 (25365 white, 3109 black) post-MELD,with a significant increase in the proportion of black recipients from 7.7% pre-MELD to10.9% post-MELD (χ2=137.78, p,.01). Compared to pre-MELD, the post-MELD transplantrecipients were older, more male, had more fulminant hepatic failure, and had older donors(all p,.01). In both cohorts, blacks transplant recipients were younger and more likely tobe male and have fulminant hepatic failure compared to whites (all p ,0.01). Blacks had ahigher risk of graft failure than whites in both the pre-MELD, HR=1.17 (95% CI,1.04,1.31)and post-MELD, HR=1.50 (95% CI,1.34,1.67); however, after adjusting for recipient diagno-sis and donor demographics, the excess risk associated with black race was no longersignificant in the pre-MELD group, HR 1.11 (95% CI, 0.99,1.25), whereas, post-MELD theexcess risk of graft failure among blacks remained significant, HR 1.43 (95% CI, 1.28,1.60).For whites, the risk of graft failure decreased 31% in the post-MELD era, HR=0.69 (95%CI,0.85,1.16), while the introduction of MELD conferred no such decrease in risk forblacks, HR=.92 (95% CI,0.78,1.08), even after adjustment for recipient and donor factors.Conclusions We identified an excess risk of graft failure associated with black race in a largenationally representative sample in both the pre-MELD and post-MELD eras; surprisingly,the excess risk could be explained by recipient and donor factors pre- but not post-MELD.The introduction of MELD decreased the risk of graft failure in whites but not blacks. TheMELD score has introduced a more objective approach to liver transplant selection that mayeliminate some unmeasured or subjective factors that may be important to consider withminority transplant patients.

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Chronic Kidney Disease Progression and Mortality in Liver TransplantRecipientsAlina M. Allen, W. Ray Kim, Terry M. Therneau, Chun Fan, Andrew D. Rule, Julie K.Heimbach

Background/Aims: Chronic kidney disease (CKD) is a common comorbidity in liver transplant(LTx) recipients as a result of multiple causes, such as pre-LTx renal injury and calcineurininhibitor nephrotoxicity as well as diabetes and hypertension. It is well known that CKDleads to increased mortality; however, the exact magnitude of mortality risk as a result ofreduced renal function is not defined in LTx recipients.Methods: A database that prospectivelytracks all LTx recipients at this academic transplant program from 1985 to 2011 was queriedto identify all adult primary LTx recipients. CKD has been defined by a glomerular filtrationrate (GFR) , 60 ml/min/1.73 m2 and our post-LTx protocol incorporates GFR assessmentat regular intervals. If measured GFR data were not available, it was estimated by using aformula that we previously developed for this population based on age, sex, standardizedserum creatinine and albumin and hemoglobin. Time-dependent Cox regression analysiswas performed to evaluate the impact of GFR changes on survival. Results: A total of 1860liver transplant recipients met the eligibility criteria. At the time of LTx, the median agewas 52 years, 58% were male and 78% were Caucasians. After a mean follow-up of 7.6years, 612 (32.9%) died and 58 (3.1%) underwent renal transplantation. The figure illustratesthe influence of GFR on mortality. Mortality risk does not increase when GFR remainedabove 60; however, reduction in GFR below 60 was associated with significant increase inthe risk of death. Thus, patients with a GFR of 30-59 ml/min/1.73 m2 had 1.17 fold increase(hazard ratio [HR]=1.17, 95% confidence interval [CI]=0.89-1.55) in mortality, whereas aGFR of 15-29 ml/min/1.73m2 had 2.5-fold increase (HR=2.5, 95%CI=1.8-3.45 ). Asexpected, patients with kidney failure (GFR ,15 ml/min/1.73 m2) faced extremely highmortality risk (HR=4.24, 95%CI=2.69-6.67). Conclusion: Variation in GFR .60 did nothave demonstrable effect on mortality, whereas reduction of GFR below 60 ml/min/1.73

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sm2 increased mortality in an exponential fashion. These data highlight the importance ofprevention and early recognition of CKD in LTx recipients.

Influence of GFR on mortality

625

Development and Pilot of a Checklist for Management of Acute Liver Failurein the Intensive Care UnitOren K. Fix, Iris Liou, Constantine Karvellas, Daniel Ganger, Kimberly A. Forde, Ram M.Subramanian, Alice M. Boylan, A. James Hanje, R. Todd Stravitz, William M. Lee

Background and Aims: Checklists in medicine decrease error and improve providers' adher-ence to best practices, particularly when rapid and critical decision making are required.The management of acute liver failure (ALF) in the intensive care unit (ICU) is a complex,multidisciplinary process involving multiple critical steps. We aimed to develop a checklistfor the management of ALF in the ICU that would help standardize the process and improveteamwork. Methods: Checklist development used published guidelines and expert opinion.Initial drafts were reviewed by experts and refined through consensus. We pilot tested useof the checklist at multiple sites in the US and Canada. Checklist users were asked to providean assessment of the use and quality of the checklist by anonymous survey. Results arereported using 5-point Likert scales (1=Disagree Strongly or Poor, 5=Agree Strongly orExcellent). Written comments were used to improve the checklist using an iterative processuntil no additional changes were received. Results: The checklist contains a list of recommen-dations and tasks to be performed on every ALF patient admitted to the ICU, followed bytests to be performed on admission to establish the etiology of ALF. It also contains a listof best practices organized by organ system, to be reviewed and performed on admissionand daily thereafter. 42 surveys were completed at 8 sites by a variety of practitioners inthe ICU, including fellows and faculty in hepatology, gastroenterology, surgery and criticalcare, residents in internal medicine and surgery, nurses, nurse practitioners and pharmacists.Pilot users found the checklist logical and useful and generally agreed or agreed stronglywith each survey item (see table). They rated the overall quality of the checklist as aboveaverage to excellent (mean 4.52 ± 0.59). All pilot users would use the checklist again forfuture patients. The lowest scores, while still favorable, suggested that users did not alwaysstrongly agree that the checklist allowed them the freedom to use their clinical judgment.Conclusions: The Acute Liver Failure Study Group (ALFSG) checklist for the managementof ALF in the ICU was easy to use, useful and accepted by a wide variety of practitionersat multiple sites. Although there may be a perception that the checklist could impact freedomof clinical judgment, this may be a desirable attribute for a tool designed to standardizemanagement and reduce variability across sites. A checklist is particularly suited to a complexbut rare critical illness where providers are unlikely to have significant prior experiencewith the condition. The impact of the use of the ALFSG checklist on the management ofALF is the subject of future study.

ALF, acute liver failure

629

A New Staging System for Perihilar CholangiocarcinomaRoongruedee Chaiteerakij, Carlos Romero-Marrero, Joseph Kaiya, William S. Harmsen,Terry M. Therneau, William Sanchez, Lewis R. Roberts, Gregory J. Gores

BACKGROUND: Current staging systems for perihilar cholangiocarcinoma (pCCA) are inade-quate as they are based on surgical pathology, and therefore, are not relevant to unresectablepatients. A broader staging system based on clinical variables is needed to address thisdeficiency. Thus, our AIMs were to create a new clinical staging system for pCCA patients

S-956AASLD Abstracts

which would be of prognostic relevance and help stratify patients for clinical trials. METH-ODS: All pCCA patients seen at Mayo Clinic, Rochester, MN between 2002 - 2006 wereidentified (n=284). Demographic, clinical, laboratory and radiographic data were abstractedfrom the medical record. A model for predicting outcome was developed using Cox propor-tional hazards analysis methods, with overall survival as the primary endpoint. Patients withincomplete data or who were treated with resection or systemic chemotherapy prior to theirfirst Mayo Clinic visit (n=54) were excluded from the analysis. RESULTS: A total of 230pCCA patients were included in the analysis. ECOG performance status, identification of amass lesion, lobar atrophy, vascular encasement, and metastasis were significant predictorsof mortality. These variables were grouped into a 4-level staging system (see enclosed Table).Hazard ratios (95% confidence interval) of death for pCCA stages I, II, III, and IV were 1.0(reference), 1.6 (1.0-2.4), 2.7 (1.6-4.5), and 4.3 (2.9-6.3), respectively (p ,0.0001). Themedian survivals of pCCA patients in stages I, II, III, and IV were 27.7, 14.7, 11.0 and 4.9months, respectively (p,0.0001). Of the patients who had obstructive jaundice that wasinitially treated by stenting, those whose bilirubin improved substantially within 30 daysafter initial stenting (defined as a decrease of at least 50% or to a total bilirubin , 3 mg/dL) had significantly better survival than those whose bilirubin did not improve (7.8 vs 4.2months, p = 0.001). CONCLUSIONS: Clinical trials for potential targeted therapies arehampered by the lack of an accurate, non-operative staging system that predicts survival ofpatients with pCCA. We have developed a staging system based upon clinical and radiologicfindings for pCCA which divides patients into four discrete, prognostic stages and shouldbe useful to clinicians and design of clinical trials.Proposed staging system for perihilar cholangiocarcinoma

NA, not applicable; ECOG, Eastern Cooperative Oncology Group; LN, lymph node

630

Coffee Consumption Is Associated With Reduced Risk of Primary SclerosingCholangitis but Not Primary Biliary CirrhosisCraig Lammert, Brian D. Juran, Erik Schlicht, Xiao Xie, Elizabeth J. Atkinson, Mariza deAndrade, Konstantinos Lazaridis

Background: Coffee consumption has recently been associated with multiple health benefitsincluding protective effects in the liver and has been reported to reduce risk of clinical andpathologic fibrosis in chronic liver disease. Despite these observations, a detailed evaluationof coffee use among individuals with cholestatic liver disease is lacking. Therefore, we aimedto assess potential associations between coffee consumption and risk of primary biliarycirrhosis (PBC) and primary sclerosing cholangitis (PSC). Methods: Adult patients with well-defined PBC and PSC as well as otherwise healthy controls undergoing routine physicalexamination in primary care were recruited at our institution from 2002 to 2012 for studyparticipation. A coffee questionnaire (CQ) was mailed to our PBC, PSC patients and controls.The CQ was composed of 10 questions detailing current coffee drinking status and lifetimecoffee use. Statistical analyses of case (PBC or PSC) and control responses were completedutilizing chi-square and rank sum tests. Logistic regression was used to adjust the resultsfor age and sex. Results: Analysis of the CQ was completed using a total of 530 PBC, and348 PSC patients as well as 456 controls (response rate of 78%, 68%, and 77%, respectively).PBC cases and controls were significantly different in terms of sex (% female: 89% vs.74%,p , 0.001), but age at survey completion was similar (66 vs. 66 years, p = 0.9). Percentageof current coffee drinkers and never coffee drinkers did not differ among the groups (p =0.11). There was also no difference between coffee drinkers among PBC cases and controlsin terms of mean age at coffee start, estimated lifetime cups/month, and percent of lifeconsuming coffee. Comparison of PSC cases and controls revealed a significant differencein not only sex composition (p = 0.001), but also age at survey completion (57 vs. 66 years,p , 0.001). 21% of PSC patients and 13% of controls reported never drinking coffee and67% of PSC patients compared to 78% of controls were current coffee drinkers (p , 0.001).This difference remained significant after adjusting for age and sex (p = 0.01). On average,PSC cases consumed 50 cups/month and had spent 50% of their life actively drinking coffeewhereas controls consumed 78 cups/month and had spent 67% of their life drinking coffeeafter adjusting for age and sex (p , 0.01). Conclusions: We present findings supportingthat coffee consumption provides a protective benefit against the development of PSC butnot PBC. The identification of coffee as a protective factor in PSC and not PBC revealsanother environmental effect divergence between these disorders and highlights importantdisease discrepancies. Further dissection of these relationships may assist in elucidating keypathogenetic differences between these cholestatic liver diseases.