On June 18, 2013, the United Network for Organ Sharing (UNOS) instituted a change in the liver transplant allocation policy known as "Share 35." The goal was to decrease waitlist mortality by increasing regional sharing of livers for patients with a model for end-stage liver disease (MELD) score of 35 or above. Several studies have shown Share 35 successful in reducing waitlist mortality, particularly in patients with high MELD. However, the MELD score at transplant has increased, resulting in sicker patients, more complications, and longer hospital stays. Our study aimed to explore factors, along with Share 35, that may affect the cost of liver transplantation. Our results show Share 35 has come with significantly increased cost to transplant centers across the nation, particularly in regions 2, 5, 10, and 11. Region 5 was the only region with a median MELD above 35 at transplant, and cost was significantly higher than other regions. Several other recipient factors had changes with Share 35 that may significantly affect the cost of liver transplant. While access to transplantation for the sickest patients has improved, it has come at a cost and regional disparities remain. Financial implications with proposed allocation system changes must be considered.

Welcome to the inaugural issue of the Journal of Renal and Hepatic Disorders. The aim of the journal is to promote the study and dissemination of research involving both renal and hepatic organ systems and their impact on the whole organism in both healthy and diseased states. In addition, the focus of the journal will provide a unique forum in which the interdependence and interactions between the liver and kidney will be of particular interest.

Expanded criteria donor kidneys (ECD) have the potential to greatly increase the number of kidneys available for transplantation; however utilization is limited by poorer outcomes [1-5]. One strategy to improve outcomes and secondarily utilization is improved matching of kidneys based on recipient factors such as surface area [6,7], kidney graft size to recipient weight [8] and kidney weight to recipient weight [9,10]. Recently our group developed the creatinine clearance match ratio (CCMR) as an improved matching technique. The CCMR is calculated using a manipulation of the Cockcroft-Gault equation estimating the creatinine clearance required by the recipient at a serum creatinine level of 1.0 thereby producing an estimated value for an individual’s creatinine production and in intellectual shorthand, “nephron need” [11,12]. We simply asked; “how much Creatinine clearance would a potential recipient require to achieve a post-transplant serum creatinine of 1.0,” and then created a variable utilizing Cockcroft-Gault estimated donor creatinine clearance from known donor variables. Simplification results in the equation below.

Pompe disease results from inherited deficiency of the enzyme acid alpha-glucosidase resulting in lysosomal accumulation of glycogen primarily in skeletal muscle. Reported is the first case in which a donor with late onset Pompe disease (LOPD) was successfully used for deceased donor liver and kidney transplantation. This case demonstrates co-operative transplant surgery and genetic medicine evaluation and risk estimation for donors with inherited metabolic disorders some of which may be suitable for donation of selected organs for transplantation.

Improved outcomes have been associated with various methods of size matching between expanded criteria (ECD) donors and recipients. A novel method for improved functional based matching was developed utilizing manipulation of Cockcroft-Gault estimated creatinine clearances for donor and recipient. We hypothesized that optimal clearance-based matches would have superior outcomes for both immediate graft function and long-term graft survival. For the analysis, recipients of ECD kidneys in the Scientific Registry of Transplant Recipients (SRTR) transplanted between October 1, 1987 and August 31, 2011 were included. Univariate and multivariate analyses predicted the hazard ratio of graft failure and the odds ratio of requiring dialysis within the first week. A total of 25,640 ECD kidney transplants were analyzed. On multivariate analysis, higher creatinine clearance match ratio (CCMR) was associated with increased graft failure and odds of requiring dialysis within the first week (comparing highest ratio quintile versus lowest ratio quintile: HR 1.43, p < 0.001; OR 2.08, p < 0.001). This study suggests that ECD kidneys have improved outcomes when the recipient/donor CCMR is optimized.

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

AIM To hypothesize that the product of calculated Model for End-Stage Liver Disease score excluding exception points and donor age (D-MELD) risk capping ± Rule 14 could improve post liver transplant and overall survival after listing. METHODS Probabilities derived from the United Network for Organ Sharing database between 2002 and 2004 were used to simulate potential outcomes for all patients listed for transplantation. The Markov simulation was then modified by screening matches using a 1200 or 1600 D-MELD risk cap ± allowing transplants for Model for End-Stage Liver Disease (MELD) ≤ 14 (Rule 14). The differential impact of the rule changes was assessed. RESULTS The Markov simulation accurately reproduced overall and post transplant survival. A 1200 D-MELD risk cap improved post-transplant survival. Both the 1200 and 1600 risk caps improved overall survival for waitlisted patients. The addition of Rule 14 further improved post transplant and overall survival by redistribution of donor livers to recipients in higher MELD subgroups. The mechanism for improved overall and post-transplant survival after listing was due to shifting a larger percentage of transplants to the moderate MELD score subgroup (MELD 15-29) while also ensuring that high MELD recipients have livers of high quality to achieve excellent post transplant survival. CONCLUSION A 1200 D-MELD risk cap + Rule 14 provided the greatest overall benefit primarily by focusing liver transplantation towards the moderate MELD recipient.

Body: Based on an intention to treat model, we have shown that simultaneous liver kidney (SLK) transplantation offers significantly better graft and patient survival than liver transplantation alone (LA) in patients listed for SLK. SLK transplantation in the setting of retransplantation may increase risk due to increased surgical difficulty, cold ischemia time, and immunological risk. We hypothesized that retransplants (ReTx) will have worse outcomes in patients listed for SLK transplants. Methods: Using UNOS STAR files, all 4867 patients listed for SLK from 7/1988 to 10/2012 were analyzed. There were 4091 SLK primary transplants (SLK and No ReTx), 596 LA primary transplants (LA and No ReTx), 141 SLK retransplants (SLK and ReTx), and 39 LA retransplants (LA and ReTx). Kaplan Meier analysis, the log rank test, and Cox multivariate analysis were used. Results: In patients listed for a SLK, there was significantly lower patient and liver graft survival in ReTx compared to primary SLK.Figure: No Caption available.Table: No Caption available.In the multivariate model, era, pediatric, and recipient and donor gender were not statistically significant risk factors. However, LA and no ReTx (RR = 1.9, p < 0.0001), SLK and ReTx (RR = 1.6, p < 0.0001), LA and ReTx (RR = 3.8, p < 0.0001) were statistically significant risk factors for worse graft survival. In addition, donor age (RR = 1.014, p < 0.0001), recipient age (RR < 1.007, p < 0.01), DCD (RR = 1.7, p < 0.0001) and cold ischemia (1.015, p = 0.03) were significant risk factors. Conclusions: For patients listed for SLK, retransplantation, especially LA retransplantation, results in significantly inferior patient and liver graft survival compared to primary SLK. Recipient and donor age, DCD, and CIT also appear to be important risk factors in this population.

Under the current liver organ allocation system organs are on a sickest first policy as prioritized by MELD score within one of the 11 multi-state UNOS regions for MELD scores greater than 35. In the unusual circumstance in which no patient has a MELD score above 35, the organ is offered within a local area, again prioritized by the MELD score. Both UNOS regions and local distribution areas called DSAs (Donor Service Areas) may be served by several transplant centers creating a competitive environment for organ placement primarily between transplant centers acting as proxy for their listed patients. Although donor livers are offered for recipients based solely on urgency as defined by the MELD score, centers and patients are free to accept or reject offers based on their personal estimate for successful transplantation.

Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p = 0.0062, OR = 0.15, 95% CI (0.04, 0.59)). ICU (p = 0.47) and hospital length of stay (p = 0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were $1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010.

Purpose: To determine the incidence and management of NAFLD and NASH in prescreened living kidney donors. Methods: Between January 2010 and December 2013, 399 potential kidney donors were registered and underwent blood and HLA typing at our institution. Of these potential donors, 106 completed the evaluation including computed tomography (CT) scan. Diagnosis of NAFLD was based upon presence of hepatic steatosis on imaging using liver to spleen ratio (L:S ratio, <1.1) criteria, and absence of anti-HCV and HBsAg, and negative history of excessive alcohol use, and secondary causes of hepatic steatosis or other causes of elevated serum ALT or AST (LFTs). 14 patients (13.2%) had elevated ALT, TB or AST, and 10 patients (9.4%%) had hepatic steatosis noted on CT. 6 patients (5.6%) had both abnormal LFTS and hepatic steatosis on imaging. Results: From the group with abnormal LFTs or imaging, 8 patients (44%) proceeded to donation. Patients with mild steatosis and normal BMI and LFTs were allowed to donate (2). 2 patients had normalization of LFTs without intervention. 3 patients with mild transaminase elevation and/or mild steatosis on imaging were counseled about diet and weight loss, and allowed to donate once transaminases normalized. Average weight loss was 8 lbs. A patient with persistent abnormal LFTs, but normal BMI and imaging was referred for a liver biopsy examination. Liver biopsy showed mild (5-10%) steatosis without signs of NASH and he was cleared for donation. 10 patients were not cleared for donation. 4 patients were ruled out for medical or anatomic issues without work up of for liver disease. One patient was referred to hepatology and but had improvement in LFTs after weight loss, however was ruled out due to the presence of nephrolithiasis. 5 patients were excluded based upon on the presence of significant liver disease. One patient was found to have alcohol abuse as likely contributing factor for liver disease. 2 patients did not proceed with their evaluation after being referred to hepatology for further work up and liver biopsy. 2 patients had NASH without cirrhosis on liver biopsy and were excluded from donation. Conclusion: 10 - 13% of healthy potential living kidney donors are found to have NAFLD based upon either elevated ALT/AST or imaging during work up. Patients with mild transaminase elevation or mild steatosis on imaging are likely ok to proceed with donation, especially if diet and weight loss leads to normalization of ALT and AST. Patients with significant steatosis on imaging or persistent elevation

Donor-2-Recipient match (D2Rm) remains subject to debate in liver transplantation. A comparative analysis of D2Rm between Italy and US has not been performed. D-MELD (product of donor-age × biochemical MELD) has been used to identify poor matches. Individual prediction of prognosis using D-MELD can be achieved using specifically developed applications (www.D-MELD.com; i-phone/i-pad D-MELD app).

BACKGROUND:Vascular complications, most commonly arterial or venous thrombosis, are one of the most common causes of early graft loss after pancreas transplantation. However, only a few cases of pseudoaneurysm formation have been reported.CASE REPORT:This case report is unique for the presentation of pancreatic graft pseudoaneurysm with a sentinel retroperitoneal bleed as well as the failure to achieve diagnosis by ultrasound or standard cut CT scanning. The case emphasizes the importance of clinical suspicion and the need for dedicated fine-cut CT angiography or standard percutaneous angiography for diagnosis. The site of the anastomosis precluded minimally invasive treatment options and open repair with graft salvage was accomplished with minimal morbidity.CONCLUSIONS:Although pseudoaneurysm after pancreas transplantation is uncommon, unexplained post-operative bleeding, even in the stable patient, should raise the suspicion of a sentinel bleeding event necessitating urgent angiography. Rapid diagnosis and treatment can prevent potential life- and graft-threatening rebleeding. The choice between minimally invasive and open surgical repair should be individualized depending on the site of the lesion.