Taner, C. Burcin

The tragedy of the national opioid epidemic has resulted in a significant increase in the number of opioid‐related deaths and accordingly an increase in the number of potential donors designated Public Health Service (PHS) increased risk. Previous studies have demonstrated reluctance to use these PHS organs, and as a result, higher discard rates for these organs have been observed. All patients listed for liver transplantation in the United States from January 2005 to December 2016 were investigated. Patients on the waiting list were divided into 2 groups: those in which a PHS liver was used for transplantation (accepted PHS group) and those in which a PHS liver was declined and transplanted into a recipient lower on the match run (declined PHS group). Intention‐to‐treat patient survival from the time of PHS offer was significantly higher in the accepted PHS compared with the declined PHS group (P < 0.001). On Cox multivariate regression, declining a PHS donor liver was associated with a hazard ratio of 2.36 (95% confidence interval, 2.23‐2.49; P < 0.001). For patients in which a PHS organ offer was declined, 11.6% died or were delisted for being too sick within the subsequent year. Donor liver allografts implanted in the accepted PHS group were of a lower donor risk index (1.28 versus 1.44) compared with the non‐PHS organs that patients in the declined PHS group ultimately received if they underwent transplantation. In conclusion, there is a significantly higher survival for patients in which a PHS liver is accepted and used compared with those patients in which a PHS organ is declined. These data will help inform decisions about whether or not to accept a PHS donor liver for both patients and transplant professionals. Liver Transplantation 24 497–504 2018 AASLD.

In experimental hypercholesterolemia, endothelium-dependent relaxations decrease, as does endothelial immunoreactivity for nitric oxide (NO) synthase (NOS; eNOS) in coronary arteries. Systemic levels of NO also decrease with concomitant elevations in systemic circulating levels of endothelin (ET)-1. Chronic treatment of hypercholesterolemic pigs with ET-receptor antagonists increases circulating NO and improves endothelium-dependent relaxations. Mechanisms causing these increases are not known. Therefore, experiments were designed to test the hypothesis that chronic administration of ET-receptor antagonists to hypercholesterolemic pigs increases NO production through increases in NOS activity. Female juvenile pigs were fed a 2% cholesterol atherogenic diet and were randomly allocated to receive no treatment (controls), a selective ET A -receptor antagonist (ABT-624), or a combined ET A + ET B -receptor antagonist (RO-48-5695) daily for 12 wk. After 12 wk, endothelial cells from thoracic aorta were prepared for measurement of eNOS mRNA or eNOS activity. Total cholesterol, low-density-lipoprotein cholesterol, and concentrations of ET-1 were significantly higher in all three groups at 12 wk compared with baseline levels. Circulating plasma-oxidized products of NO (NOx) increased with ET-receptor blockade. NOS mRNA was similar among groups. Total and Ca-dependent NOS activity was significantly higher in aortic endothelial cells from the ET A + ET B -treated pigs compared with those treated with ET A antagonist alone. These results suggest that changes in systemic NOx after chronic inhibition of ET A + ET B receptors in hypercholesterolemia may result from posttranscriptional changes in NOS.

The use of liver grafts from donation after cardiac death (DCD) has been limited due to the increased rate of graft failure, mostly related to ischemic cholangiopathy (IC). It is our hypothesis that longterm outcomes and quality of life (QOL) similar to patients undergoing liver transplantation (LT) with donation after brain death (DBD) can be achieved. Clinical outcomes of all patients undergoing DCD LT (n = 300) between 1998 and 2015 were compared with a propensity score–matched cohort of patients undergoing DBD LT (n = 300). Patients were contacted for a follow‐up questionnaire and short‐form (SF)–12 QOL Survey administration. Median follow‐up was >5 years. Graft survival at 1‐, 3‐, and 5‐years was 83.8%, 75.5%, and 70.1% in the DCD LT group and 88.4%, 80.3%, and 73.9% in the DBD LT group ( P = 0.27). Patient survival at 1‐, 3‐, and 5‐years was 92.3%, 86.1%, and 80.3% in the DCD LT group and 92.3%, 85.1%, and 79.5% in the DBD LT group ( P = 0.81). IC developed in 11.7% and 2% of patients in the DCD LT group and DBD LT group, respectively ( P < 0.001). DCD LT recipients who developed IC had inferior graft survival compared with both the DCD non‐IC group ( P < 0.001) and the DBD LT group ( P < 0.001); no difference in graft survival was observed between the DCD non‐IC group and the DBD LT group ( P = 0.50). Physical and Mental Composite Scores on the SF‐12 QOL questionnaire were similar between the DCD LT and DBD LT groups (44.0 versus 45.4; P = 0.34 and 51.9 versus 52.2; P = 0.83), respectively. Similar longterm survival and QOL scores can be achieved between DCD LT and DBD LT. Prevention of IC in DCD LT yields excellent graft and patient survival with virtually no difference compared with DBD LT. Liver Transplantation 23 342–351 2017 AASLD .

AbstractKidney transplant (KT) programs have extended recipient eligibility to those who were previously excluded due to advanced age. We aimed to determine the outcomes of the patients ≥70 years undergoing KT and investigate factors predicting survival. Two thousand six hundred and twenty‐four KT patients between 2003 and 2013 at two institutions were divided into two groups; those ≥70 years (n=300) and those <70 years (n=2324) at the time of KT. Patient survival at 1, 3, and 5 years was 95%, 86%, and 77% in ≥70 years of age group and 98%, 95%, and 90% in the <70 years group (P<.001). When graft loss due to death was censored, graft survival was not significantly different between the two groups (P=.18). On multivariable analysis, the significant predictors of inferior survival in patients ≥70 years included: body mass index (BMI)>30 kg/m2 (hazard ratio [HR] 1.07; P=.01), panel reactive antibody (PRA)>20% (HR 2.38; P=.01), previous coronary artery bypass grafting (CABG; HR 1.95; P=.03) and peripheral vascular disease (PVD; HR 2.60; P=.04). Acceptable outcomes can be achieved in KT recipients ≥70 years. Caution should be used when listing these patients if they have BMI>30 kg/m2, PRA>20%, CABG or PVD.

Although there is an agreement that liver grafts from pediatric donors (PDs) should ideally be used for pediatric patients, there remain situations when these grafts are turned down for pediatric recipients and are then offered to adult recipients. The present study aimed to investigate the outcomes of using these grafts for liver transplantation (LT) in adult patients. Data from all patients undergoing LT between 2002 and 2014 were obtained from the United Network for Organ Sharing Standard Analysis and Research file. Adult recipients undergoing LT were divided into 2 groups: those receiving a pediatric liver graft (pediatric‐to‐adult group) and those receiving a liver graft from adult donors (adult‐to‐adult group). A separate subgroup analysis comparing the PDs used for adult recipients and those used for pediatric recipients was also performed. Patient and graft survival were not significantly different between pediatric‐to‐adult and adult‐to‐adult groups (P = 0.08 andP = 0.21, respectively). Hepatic artery thrombosis as the cause for graft loss was higher in the pediatric‐to‐adult group (3.6%) than the adult‐to‐adult group (1.9%;P < 0.001). A subanalysis looking at the pediatric‐to‐adult group found that patients with a predicted graft‐to‐recipient weight ratio (GRWR) < 0.8 had a higher 90‐day graft loss rate than those with a GRWR ≥ 0.8 (39% versus 9%;P < 0.001). PDs used for adult recipients had a higher proportion of donors with elevated aspartate aminotransferase/alanine aminotransferase (20% vs. 12%;P < 0.001), elevated creatinine (11% vs. 4%;P < 0.001), donation after cardiac death donors (12% vs. 0.9%;P < 0.001), and were hepatitis B virus core positive (1% vs. 0.3%;P = 0.002) than PDs used for pediatric recipients. In conclusion, acceptable patient and graft survival can be achieved with the use of pediatric liver grafts in adult recipients, when these grafts have been determined to be inappropriate for usage in the pediatric population.Liver Transplantation 22 1099–1106 2016 AASLD

Although the consequences of implantation of a large whole liver graft into a small recipient such as compression and compromise of graft perfusion are well known, no accepted measure to aid in donor‐to‐recipient size matching exists. Donor liver graft and recipient native liver weights as well as donor and recipient size and amount of ascites were investigated in 1953 patients who underwent liver transplantation using deceased donor grafts between January 2002 and July 2013. We used a previously described formula for liver resections (standardized total liver volume [sTLV] = –794.41 + 1267.28 × body surface area [m2]) for calculating sTLV, in the current cohort of deceased liver donors. Early allograft dysfunction (EAD) and graft survival were the primary outcome measures. The formula for calculating sTLV for liver resections was validated as an accurate predictor of liver volume in the current cohort of deceased liver donors (r2 = 0.45;P < 0.001). A cutoff point of sTLV ratio ≥ 1.25 was determined through receiver operating characteristic curves, and patients were dichotomized into 2 groups. In the sTLV ratio ≥ 1.25 group, 50% of patients developed EAD compared to 25% of patients in the sTLV ratio < 1.25 group (P < 0.001). The proportion of patients developing graft failure within 90 days was 9.6% in the sTLV ratio ≥ 1.25 group and 5.4% in the sTLV ratio < 1.25 group (P = 0.045). This study validates the use of the sTLV for prediction of actual donor liver weight in the transplant setting. Using this formula, donors with a calculated sTLV size ratio ≥ 1.25 have an increased risk of EAD and therefore caution should be used when that value is exceeded. This adjusted size ratio can be used as a decision aid when considering donor and recipient matching with potential liver organ offers.Liver Transpl 21:1471‐1477, 2015. © 2015 AASLD.