Shorter Height is Associated with Lower Probability of Liver Transplantation in Patients with Hepatocellular Carcinoma Background: The effect of height and sex on liver transplantation (LT) for hepatocellular carcinoma (HCC) remains unclear. Methods: Using United Network for Organ Sharing (UNOS) data, 14,844 HCC patients listed for LT from 2005-2015 were identified. Cumulative incidence of waitlist events (LT and dropout for death or too sick) were calculated and modeled using Fine and Gray competing risk regression. Results: Short (SWR), Mid (MWR) and Long (LWR) UNOS wait regions comprised 25%, 42%, and 33% of the cohort. Three-year cumulative incidence of LT was lower in shorter height patients (≤150, 151-165, and >185 cm; 70.8%, 76.7%, and 83.5%, p<0.001) and women (78.2% vs 79.8%, p<0.001) and. On multivariable analysis, shorter height (≤150, 151-165 cm, HR versus >185 cm) was associated with lower probability of LT (0.81 and 0.89, p=0.02) and greater dropout (HR 1.99 and 1.43, p<0.001). Female sex was not associated with LT overall, but a significant sex and wait region interaction (p=0.006) identified lower LT probability for women in MWR (HR versus men, 0.91, p=0.02). Conclusion: Despite uniform HCC MELD exception across height and sex, shorter patients and females in MWR have lower probability of LT. Consideration should be given to awarding additional MELD exception points to these patients. Disclosures: None of the authors have any relevant potential conflicts of interest to disclose Financial Support: This work was supported by the Clinical and Translational Core of the UCSF Liver Center (P30 DK026473). Corresponding Author: Neil Mehta, M.D., University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0538, E-mail: neil.mehta@ucsf.edu Tel: (415)-476-2777, Fax: (415)-476-0659 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Randomized Sirolimus-based early calcineurin inhibitor reduction in liver transplantation: impact on renal function Background. The long-term use of calcineurin inhibitors (CNI) after liver transplantation (LT) is associated with nephrotoxicity. Methods. 5-year follow-up data was retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mTOR-free immunosuppression (group A, n=264) was compared to a 50 % reduction of CNI and introduction of the mTOR inhibitor Sirolimus within 4 to 6 weeks after LT (group B, n=261). Results. Median MELD at LT was low with 10 (7 - 15) (group A) and 11 (8 - 15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months post transplantation. Renal function was preserved at 3 months after LT in the Sirolimus arm [eGFR 74 (57-95) versus 67 (55-85) ml/min/1.73m2, p=0.004] but was similarly impaired thereafter compared to group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and Sirolimus treatment ≥ year 1 with significantly superior eGFR and lowest rate of chronic kidney disease (≥ stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder and hyperglycemia) were not associated with worse kidney function. Conclusions. Prevention of CNI nephrotoxicity by Sirolimus-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and Sirolimus maintenance achieved better long-term renal outcomes compared to real-world practice. * The SiLVER study investigators that are not authors of this work are listed under Acknowledgments. Clinical Trial Number EudraCT: 2005-005362-36; Clinicaltrials.gov: NCT00355862 Funding: This investigator initiated trial (SiLVER) was supported by a research grant from Pfizer Inc. to EKG and sponsored by the University Hospital Regensburg, Germany. Disclosure: EKG has received speaking fees from Novartis. AAS received travel support from Pfizer. BMB, JWF, PN, HJS and DFM declare no conflict of interest. Correspondence/Reprints: Prof. Darius F Mirza, Consultant Liver Transplant Surgeon, Liver Unit, Queen Elizabeth Hospital Birmingham and Birmingham Childrens’ Hospital, Mindelsohn Way, Birmingham, United Kingdom B15 2TH., Phone +44 (121) 697-8391, Email: Darius.Mirza@uhb.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A case of hidroacanthoma simplex in a cardiac transplant recipient No abstract available

Posttransplant outcomes for cPRA-100% recipients under the new Kidney Allocation System Background: There is concern in the transplant community that outcomes for the most highly sensitized recipients might be poor under KAS high-prioritization. Methods: To study this, we compared posttransplant outcomes of 525 pre-KAS (12/4/2009-12/3/2014) cPRA-100% recipients to 3026 post-KAS (12/4/2014-12/3/2017) cPRA-100% recipients using SRTR data. We compared mortality and death-censored graft survival using Cox regression, acute rejection and delayed graft function (DGF) using logistic regression, and length of stay (LOS) using negative binomial regression. Results: Compared to pre-KAS recipients, post-KAS recipients were allocated kidneys with lower KDPI (median 30% vs. 35%, p<0.001) but longer cold ischemic time (median 21.0 hours vs. 18.6, p<0.001). Compared to pre-KAS cPRA-100% recipients, those post-KAS had higher 3-year patient survival (93.6% vs. 91.4%, p=0.04) and 3-year death-censored graft survival (93.7% vs. 90.6%, p=0.005). The incidence of DGF (29.3%vs. 29.2%, p=0.9), acute rejection (11.2% vs. 11.7%, p=0.8), and median LOS (5 days vs. 5, p=0.2) were similar between pre-KAS and post-KAS recipients. After accounting for secular trends and adjusting for recipient characteristics, post-KAS recipients had no difference in mortality (adjusted hazard ratio [aHR]: 0.861.623.06, p=0.1), death-censored graft failure (aHR: 0.521.001.91, p>0.9), DGF (adjusted odds ratio [aOR]: 0.580.861.27, p=0.4), acute rejection (aOR: 0.610.941.43, p=0.8), and LOS (adjusted LOS ratio: 0.981.161.36, p=0.08). Conclusion: We did not find any statistically significant worsening of outcomes for cPRA-100% recipients under KAS, although longer-term monitoring of posttransplant mortality is warranted. DISCLOSURES:The authors of this manuscript have no conflicts of interest to disclose as described by Transplantation FUNDING:This work was supported by grant numbers F32DK113719 (Jackson), F32DK109662 (Holscher), K01DK101677 (Massie), K23DK115908 (Garonzik-Wang), and K24DK101828 (Segev) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dr. Holscher is supported by the American College of Surgeons Resident Research Scholarship. Correspondence: Dorry Segev, M.D., Ph.D., Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology, Associate Vice Chair, Department of Surgery, Director, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University, 2000 E Monument St., Baltimore, MD 21205, 410-502-6115 (tel) 410-614-2079 (fax), dorry@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Liver transplantation for hepatic epithelioid hemangioendothelioma is facilitated by exception points with acceptable long-term outcomes Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with a high mortality rate. HEHE is now a formally recognized indication for exception point priority in the U.S. under the new National Liver Review Board. The role of liver transplantation (LT) and exception point waitlist priority in the U.S. for patients with HEHE remains understudied. Methods: This was a retrospective cohort study using the United Network for Organ Sharing transplant database. From 2/27/02-1/31/18, 131 adults waitlisted for LT with HEHE were identified by free-text entry. Results: Exception point applications were submitted for 91.6% (120/131) of patients. All patients with fully reviewed applications received exception points at least once during waitlisting, and 85% (103/120) upon first submission. Among the 88 patients transplanted, median Model for End-stage Liver Disease (MELD) score at LT was 7 (IQR: 6-11) and waiting time 78.5 days [IQR: 29.5-237.5]. Unadjusted post-LT survival of HEHE recipients at 1-, 3- and 5-years from LT was 88.6%, 78.9% and 77.2%. Unadjusted post-LT patient and graft survival of HEHE patients was not different from patients with hepatocellular carcinoma within Milan receiving exception point priority (p=0.08). An increased rate of graft failure due to hepatic artery thrombosis ≤14 days from initial LT was observed in HEHE versus non-HEHE patients (4.6% vs 0.5%). Conclusions: The majority of HEHE recipients receive exception points at a universal approval rate allowing prompt access to deceased donor LT. Disclosure: The authors declare no actual or potential conflicts of interest for this study. Funding: This study received no external funding. Correspondence Information: Therese Bittermann, MD, MSCE, Hospital of the University of Pennsylvania, Penn Transplant Institute, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, Email: therese.bittermann@pennmedicine.upenn.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Macrosteatotic Allografts and Obese Recipients Have Nearly Equal Negative Impact on Liver Transplant Survival Background: Our aim was to evaluate liver transplant outcomes involving donors with high macrosteatosis grafts in the obese modern liver transplant recipient population. Methods: A high-steatosis graft was defined as donor graft macrosteatosis ≥ 30% on biopsy. Recipient obesity was defined as body mass index (BMI) > 35 adjusted for ascites. Raw and adjusted recipient liver transplant survival were evaluated and compared between four cohorts: 1) High-steatosis graft in high-BMI recipient, 2) Low-steatosis graft in high-BMI recipient, 3) High-steatosis graft in normal-BMI recipient, 4) Low-steatosis graft in normal-BMI recipient. Results: After adjustment for multiple factors, recipient high-BMI remained an independent predictor of post-transplant mortality at 30 days (p<0.0001) and persisted at one year (p=0.009). A high-steatosis graft was the strongest independent predictor of mortality at 30 days (HR 2.05, 1.66-2.53, p<0.0001) and that effect was diminished but persistent at one year (1.27, 1.10-1.46, p=0.001). Conclusions: Recipient high-BMI and a high-steatosis graft are both significant independent and equally powerful predictors of mortality after modern liver transplant. High-steatosis grafts transplanted into obese recipients have the highest mortality. The increase in mortality associated with a high-steatosis graft into a normal-BMI recipient is similar in magnitude to a low-steatosis graft placed into a high-BMI recipient. Authors’ contributions: Northup: Conceptualization of project, statistical analysis, manuscript writing, final editorial approval. Intagliata: Statistical analysis and review, manuscript preparation, editorial approval. Davis: Manuscript writing, editorial approval. Argo: Conceptualization, manuscript preparation, editorial approval. Pelletier: Conceptualization, manuscript preparation, editorial approval. Financial Support: No financial support was used in production of this work. The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the OPTN or the U.S. Government. The authors claim no financial conflicts with the material presented here. Contact Information: Patrick Northup, MD, Division of Gastroenterology and Hepatology, University of Virginia Health System, JPA and Lee Street, MSB 2145, Charlottesville, VA 22908-0708, northup@virginia.edu, 434.243.2718 (Office)M, 434.244. 9254 (Fax), Author emails: nmi4d@virginia.edu, jd5uu@virginia.edu, cka3d@virginia.edu, sjp7t@virginia.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Bronchial-arterial-circulation-sparing lung preservation: A new organ protection approach for lung transplantation Background: Compromised microvasculature resulting from disrupted bronchial arterial circulation appears to trigger chronic lung allograft dysfunction (CLAD). Maintaining the microvasculature throughout the transplant process could improve the long-term health of transplanted lungs. We recently developed a bronchial-arterial-circulation-sparing (BACS) lung preservation approach and tested whether this approach would decrease microvascular damage and improve allograft function. Material and Methods: The lungs of Lewis rats were procured using either the BACS approach, where the bronchial and pulmonary arteries were synchronously perfused; a conventional approach, where only the pulmonary artery was perfused; or a conventional approach with a prostaglandin flush. After 4 hours of cold ischemia, physiologic function and vascular tone of the grafts were evaluated during ex vivo lung perfusion (EVLP), and microvasculature damage was assessed using two-photon microscopy analysis. Lung function was compared after transplant among the groups. Results: After 4 hours of cold ischemia, the BACS group exhibited significantly higher adenosine triphosphate levels and lower expression of phosphorylated myosin light chain (p-MLC), which is essential for vascular smooth muscle contraction. On EVLP, the BACS and prostaglandin groups showed lower pulmonary vascular resistance and less arterial stiffness. BACS attenuated microvasculature damage in the lung grafts as compared with conventional preservation. After transplantation, the lungs preserved with the BACS approach exhibited significantly better graft function and lower expression of p-MLC. Conclusion: Our data suggest that BACS lung preservation protects the dual circulation inherent to the lungs, facilitating robust microvasculature in lung grafts after transplantation, leading to better posttransplant outcomes. Disclosure: The authors declare no conflicts of interest. Funding: The authors declare no funding was received for this study. Competing interests: All authors declare no conflict of interests. Address for Correspondence: Norihisa Shigemura, MD, PhD. Surgical Director of Lung Transplantation and Lung Failure, Division of Cardiovascular Surgery, Temple University Health System and Lewis Katz School of Medicine, Philadelphia, PA, USA. E-mail address: Norihisa.Shigemura@tuhs.temple.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Utilizing a Hospital Based Setting to Increase Organ Donor Registrations Background: Shortages of organs for transplantation is a concern for many countries. In Australia’s “opt-in” system, people register their donation decision on the Australian Organ Donor Register (AODR) in their own time, yet less than 30% of the population have done so. Consent registrations are honored by the next-of-kin in 90% of cases, so increasing registrations will increase donated organs for transplantation. This study investigated the efficacy of offering an immediate registration opportunity in 2 hospitals, and the role that beliefs about organ donation play in registration behavior. Methods: An immediate registration opportunity was offered at a public and private hospital in NSW, Australia. Participants (N = 168) categorized as medical/healthcare (e.g. doctor, nurse) and nonhealthcare (e.g. teacher, chef) completed a measure of beliefs about organ donation, were encouraged to discuss their fears and concerns about organ donation, and given an immediate opportunity to register on the AODR. Results: 81.5% of medical/ healthcare participants who were eligible registered, and 71.5% of all eligible participants registered on the spot. Beliefs about the negative consequences of donation and concerns over the medical care given to potential donors predicted (non) registration. Medical/healthcare participants reported lower levels of fears and concerns than nonhealthcare participants. Although both groups reported strong positive beliefs about donation, these did not predict registration. Conclusions: Offering an immediate registration opportunity in 2 hospitals notably increased the number of registrations on the Australian Organ Donor Register, suggesting this is a strategy that could potentially increase registrations in opt-in donation systems. Disclosure: The authors declare no conflicts of interest. Funding: This research was funded by NSW Organ and Tissue Donation Service Correspondence information: Dr Gail Moloney, School of Health and Human Sciences, Southern Cross University, Hogbin Drive, Coffs Harbour, NSW 2450. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Association of Clinical Rejection vs. Rejection on Protocol Biopsy with Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients Background: Two or more early rejections (<1 year) or any late acute rejection (>1 year) have been associated with coronary artery vasculopathy (CAV) in pediatric heart transplant (HT) recipients. We hypothesized that clinical rejection, defined by concurrent new-onset heart failure or left ventricular systolic dysfunction is more strongly associated with future CAV than rejection diagnosed on protocol biopsy. Methods: We identified all subjects <21 years old who received first HT at Boston Children’s Hospital during 1986-2015 with at least one post-HT coronary angiogram. CAV was diagnosed using 2010 ISHLT guidelines. Time to CAV diagnosis was assessed using a Cox model with occurrence of clinical rejection analyzed as a time-varying covariate. Results: Of 228 study subjects, 106 remained rejection-free, 77 had rejection diagnosed only on protocol biopsy (≥ 2R cellular or antibody-mediated) and 45 had a clinical rejection. Subjects with rejection diagnosed only on protocol biopsy were not at higher risk of CAV (HR 1.09, 95% CI 0.54, 2.09). In contrast, clinical rejection was significantly associated with risk of CAV (HR 4.84, 95% CI 2.99, 7.83). Late rejection was associated with a higher risk of CAV (HR 4.27, 95% CI 2.42, 7.51) if it was clinical rejection but not if it was diagnosed on protocol biopsy (HR 0.83, 95% CI 0.51, 1.37). Conclusion: Clinical rejection poses a far greater risk for future CAV than rejection on protocol biopsy in pediatric HT recipients. Preventing CAV should therefore become the focus of medical management after initial treatment and resolution of clinical rejection. * EPA and JCG contributed equally to this work Disclosure: The authors declare no conflict of interest. Funding: The study was supported by Heart Transplant Research and Education Fund, Boston Children’s Hospital, MA. J.C.G. was funded by the John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School. Address for Correspondence:Tajinder P. Singh, MD, MSc, Department of Cardiology, Children’s Hospital Boston, Tel: 617-355-0558; FAX: 617-734-9930, Email: TP.Singh@cardio.chboston.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Oral and Inhaled Ribavirin Treatment for Respiratory Syncytial Virus Infection in Lung Transplant Recipients Background: Respiratory syncytial virus (RSV) infection in lung transplant recipients (LTRs) causes mortality rates of 10-20% despite antiviral therapy. Ribavirin (RBV) has been used to treated RSV infected LTRs with limited data. Methods: A retrospective study including all LTRs at Duke Hospital during January 2013-May 2017 with positive RSV PCR respiratory specimens was performed. Results: Fifty six of 70 patients in the oral RBV group and 29 of 32 in the inhaled RBV group had symptomatic RSV infection. One patient receiving oral RBV had to prematurely stop drug due to significant nausea and vomiting. While unadjusted all-cause one-year mortality was significantly higher in the inhaled RBV group [24.1% vs 7.1% (oral RBV), p 0.03], adjusted hazard ratio (HR) for death and oral RBV use (compared to inhaled RBV), accounting for oxygen requirement and need for mechanical ventilation, showed the HR for death and oral RBV use was 0.38 ([0.10, 1.46], p 0.38). The HR for death in patients with supplemental oxygen > 2 L/min at diagnosis was 6.18 ([1.33, 26.83], p 0.02). Kaplan-Meier curves showed patients with FEV1 decline ≥ 5% and ≥ 10% at 90 days post-RSV infection had a higher 1-year mortality (p 0.004 and p 0.001, respectively). Conclusions: Oral and inhaled RBV appear to be well tolerated in LTRs and our data supports the use of oral RBV as a safe alternative to inhaled ribavirin in LTRs. Oxygen requirement > 2 L/min at diagnosis and FEV1 decline ≥ 5% post infection may be markers for increased mortality. Disclosure: N.P. served as a consultant for Alcimed. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Funding: No funding sources to be disclosed for the study. Corresponding author: Nitipong Permpalung, Address: 601 N Wolfe Street, Carnegie Building room 340, Baltimore, MD, 21231, USA. Business telephone: 443-287-6217; fax: 410-955-0788, Email: npermpa1@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.