Estimating the potential pool of uncontrolled DCD donors in the United States.

Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all-payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454-10 202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor-recipient combination.

The impact of donor quality on post-kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post-KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5-year post-KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5-year waitlist survival was 47.6%, and 5-year post-KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool (www.transplantmodels.com/kdpi-epts) can support individualized decision-making on kidney offers in clinical practice.

MELD as a metric for survival benefit of liver transplantation.

Currently, there is debate among the liver transplant community regarding the most appropriate mechanism for organ allocation: urgency-based (MELD) versus utility-based (survival benefit). We hypothesize that MELD and survival benefit are closely associated, and therefore, our current MELD-based allocation already reflects utility-based allocation. We used generalized gamma parametric models to quantify survival benefit of LT across MELD categories among 74 196 adult liver-only active candidates between 2006 and 2016 in the United States. We calculated time ratios (TR) of relative life expectancy with transplantation versus without and calculated expected life years gained after LT. LT extended life expectancy (TR > 1) for patients with MELD > 10. The highest MELD was associated with the longest relative life expectancy (TR = 1.05 1.201.37 for MELD 11-15, 2.29 2.492.70 for MELD 16-20, 5.30 5.726.16 for MELD 21-25, 15.12 16.3517.67 for MELD 26-30; 39.26 43.2147.55 for MELD 31-34; 120.04 128.25137.02 for MELD 35-40). As a result, candidates with the highest MELD gained the most life years after LT: 0.2, 1.5, 3.5, 5.8, 6.9, 7.2 years for MELD 11-15, 16-20, 21-25, 26-30, 31-34, 35-40, respectively. Therefore, prioritizing candidates by MELD remains a simple, effective strategy for prioritizing candidates with a higher transplant survival benefit over those with lower survival benefit.

Racial differences in completion of the living kidney donor evaluation process.

Racial disparities in living donor kidney transplantation (LDKT) persist but the most effective target to eliminate these disparities remains unknown. One potential target could be delays during completion of the live donor evaluation process. We studied racial differences in progression through the evaluation process for 247 African American (AA) and 664 non-AA living donor candidates at our center between January 2011 and March 2015. AA candidates were more likely to be obese (38% vs 22%: P < .001), biologically related (66% vs 44%: P < .001), and live ≤50 miles from the center (64% vs 37%: P < .001) than non-AAs. Even after adjusting for these differences, AAs were less likely to progress from referral to donation (aHR for AA vs non-AA: 0.26 0.47 0.83; P = .01). We then assessed racial differences in completion of each step of the evaluation process and found disparities in progression from medical screening to in-person evaluation (aHR: 0.41 0.620.94; P = .02) and from clearance to donation (aHR: 0.28 0.510.91; P = .02), compared with from referral to medical screening (aHR: 0.78 1.021.33; P = .95) and from in-person evaluation to clearance (aHR: 0.59 0.931.44; P = .54). Delays may be a manifestation of the transplant candidate's social network, thus, targeted efforts to optimize networks for identification of donor candidates may help address LDKT disparities.

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

Donor BMI and Post-living Donor Liver Transplantation Outcomes: A Preliminary Report.

Living liver donor obesity has been considered a relative contraindication to living donation given the association with hepatic steatosis and potential for poor donor and recipient outcomes. We investigated the association between donor body mass index (BMI) and donor and recipient posttransplant outcomes. Methods: We studied 66 living donors and their recipients who underwent living donor liver transplant at our center between 2013 and 2020. BMI was divided into 3 categories (<25, 25-29.9, and ≥30 kg/m2). Magnetic resonance imaging-derived proton density fat fraction was used to quantify steatosis. Donor outcomes included length of stay (LOS), emergency department visits within 90 d, hospital readmissions within 90 d, and complication severity. Recipient outcomes included LOS and in-hospital mortality. The Student t test was used to compare normally distributed variables, and Kruskal-Wallis tests were used for nonparametric data. Results: There was no difference in donor or recipient characteristics based on donor BMI. There was no significant difference in mean magnetic resonance imaging fat percentage among the 3 groups. Additionally, there was no difference in donor LOS (P = 0.058), emergency department visits (P = 0.64), and hospital readmissions (P = 0.66) across BMI category. Donor complications occurred in 30 patients. There was no difference in postdonation complications across BMI category (P = 0.19); however, there was a difference in wound complications, with the highest rate being seen in the highest BMI group (0% versus 16% versus 37%; P = 0.041). Finally, there was no difference in recipient LOS (P = 0.83) and recipient in-hospital mortality (P = 0.29) across BMI category. Conclusions: Selecting donors with BMI ≥30 kg/m2 can result in successful living donor liver transplantation; however, they are at risk for perioperative wound complications. Donor counseling and perioperative strategies to mitigate wound-related issues should be used when considering obese living donors.

High Coronary Artery Calcium Score Is Associated With Increased Major Adverse Cardiac Events After Liver Transplantation.

Liver transplantation (LT) candidates frequently have multiple cardiovascular risk factors, and cardiovascular disease is a major cause of morbidity and mortality after LT. Coronary artery calcium (CAC) scores are a noninvasive assessment of coronary artery disease using computed tomography. This study examines CAC scores and cardiac risk factors and their association with outcomes after LT. Methods: Patients who underwent LT between January 2010 and June 2019 with a pretransplant CAC score were included in this study. Patients were divided by CAC score into 4 groups (CAC score 0, CAC score 1-100, CAC score 101-400, CAC score >400). Major adverse cardiovascular events (MACEs) were defined as myocardial infarction, stroke, revascularization, heart failure, atrial fibrillation, and cardiovascular death. Associations between CAC score and MACE or all-cause mortality within the 5-y post-LT follow-up period were analyzed using Cox regression. Statistical significance was defined as P < 0.05. Results: During the study period, 773 adult patients underwent their first LT, and 227 patients met our study criteria. The median follow-up time was 3.4 (interquartile range 1.9, 5.3) y. After 5 y, death occurred in 47 patients (20.7%) and MACE in 47 patients (20.7%). In multivariable analysis, there was no difference in death between CAC score groups. There was significantly higher risk of MACE in the CAC score >400 group, with a hazard ratio 2.58 (95% confidence interval 1.05, 6.29). Conclusions: CAC score was not associated with all-cause mortality. Patients with CAC score >400 had an increase in MACEs within the 5-y follow-up period compared with patients with a CAC score = 0. Further research with larger cohorts is needed to examine cardiac risk stratification in this vulnerable patient population.

Intraoperative Type I Acute Myocardial Infarction During Liver Transplant Requiring Intra-Aortic Balloon Pump: A Case Report.

We describe a complex case of liver transplant in a 70-year-old male patient with no known history of coronary artery disease, normal preoperative left ventricular function, and negative preoperative cardiac workup who developed progressive intra-operative left ventricular myocardial dysfunction secondary to class I acute myocardial infarction, ultimately requiring intraoperative intra-aortic balloon pump insertion to optimize myocardial perfusion. Management of myocardial ischemia was complicated by bleeding in the setting of coagulopathy necessitating correction. Once hemostasis was achieved, the patient immediately underwent coronary angiography and bare metal stent placement in the mid-left anterior descending coronary artery for an acute plaque rupture.

Temporal Trends in Utilization and Outcomes of DCD Livers in the United States.

BACKGROUND: Historically, donation after circulatory death (DCD) livers were frequently discarded because of higher mortality and graft loss after liver transplantation (LT). However, the demand for LT continues to outstrip the supply of "acceptable" organs. Additionally, changes in the donor pool, organ allocation, and clinical management of donors and recipients, and improved clinical protocols might have altered post-DCD-LT outcomes. METHODS: We studied 5975 recovered DCD livers using US Scientific Registry of Transplant Recipients data from 2005 to 2017, with a comparison group of 78 235 adult donation after brain death (DBD) livers recovered during the same time period. We quantified temporal trends in discard using adjusted multilevel logistic regression and temporal trends in post-LT mortality and graft loss for DCD LT recipients using adjusted Cox regression. RESULTS: DCD livers were more likely to be discarded than DBD livers across the entire study period, and the relative likelihood of discard increased over time (adjusted odds ratio [aOR] of discard DCD versus DBD 3.854.455.14 2005-2007, 5.225.876.59 2015-2017) despite improving outcomes after DCD LT. Mortality risk for DCD LTs decreased in each time period (compared with 2005-2007, aHR 2008-2011 0.720.840.97, aHR 2012-2014 0.480.580.70, aHR 2015-2017 0.340.430.55), as did risk of graft loss (compared with 2005-2007, aHR 2008-2011 0.690.810.94, aHR 2012-2014 0.450.550.67, aHR 2015-2017 0.360.450.56). CONCLUSIONS: Despite dramatic improvements in outcomes of DCD LT recipients, DCD livers remain substantially more likely to be discarded than DBD livers, and this discrepancy has actually increased over time. DCD livers are underutilized and have the potential to expand the donor pool.

Delayed Graft Function in Simultaneous Liver Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF. METHODS: We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis. RESULTS: The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001). CONCLUSIONS: In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.

Liver Transplantation for Severe Alcoholic Hepatitis, Updated Lessons from the World's Largest Series.

BACKGROUND: Six-month sobriety before transplantation for alcoholic liver disease is typically required but poorly supported by data. We initiated a pilot program after a report of liver transplantation for severe alcoholic hepatitis (SAH) in which the 6-month rule was waived. We previously reported early outcomes; we now provide longer follow-up in the largest cohort of early liver transplantation for SAH in the literature to date. STUDY DESIGN: Forty-six carefully selected patients with SAH underwent liver transplantation from October 2012 through July 2017; none had been abstinent for 6 months. We also examined 34 patients with alcoholic cirrhosis who received liver transplants under standard protocols with at least 6 months sobriety. We identified patient characteristics and primary outcomes of patient and graft survival, as well as alcohol recidivism. Secondary outcomes included post-transplantation infection, malignancy, and rejection. RESULTS: Compared with patients with alcoholic cirrhosis, SAH patients were younger and with shorter drinking history and higher Model for End-Stage Liver Disease scores at listing and at transplantation. Of these patients, 46% received preoperative steroids; all were nonresponders by Lille score. At a median follow-up time of 532 days (interquartile range 281 to 998 days), there were no significant differences between groups by log-rank testing of Kaplan-Meier estimates for patient and graft survival or alcohol recidivism. CONCLUSIONS: In the largest cohort of patients reported, outcomes after liver transplantation for SAH had excellent 1-year outcomes, similar to those seen in patients who received transplants with 6 months of sobriety. Recidivism was similar in the 2 groups. Early liver transplantation for SAH represents life-saving therapy for patients with otherwise high mortality, calling into question the utility of the 6-month rule in predicting outcomes in patients receiving transplants for alcoholic liver disease.

Safety of belatacept bridging immunosuppression in hepatitis C-positive liver transplant recipients with renal dysfunction.

BACKGROUND: Perioperative renal dysfunction in liver transplant recipients complicates maintenance immunosuppressive therapy, particularly in patients with hepatitis C. Calcineurin inhibitors exacerbate renal dysfunction and mammalian target-of-rapamycin inhibitors are generally avoided because of perceived perioperative risks. The authors' experience with seven liver transplant patients who received belatacept and mycophenolic acid maintenance immunosuppression is reported. METHODS: A retrospective review of adult liver transplant recipients with hepatitis C receiving belatacept was conducted under Institutional Review Board approval. All patients were Epstein-Barr virus IgG seropositive. The primary endpoint was patient and graft survival, with secondary endpoints including the incidence of acute rejection, degree of renal function recovery, and occurrence of major side effects. RESULTS: Between December 19, 2011 and January 25, 2013, seven liver transplant recipients with hepatitis C received belatacept immunosuppression in the perioperative period. The primary indication for belatacept was perioperative renal dysfunction. Belatacept was initiated between 2 and 90 days posttransplant and the duration of belatacept therapy ranged from 19 to 89 days. Patients were transitioned onto calcineurin inhibitor therapy when they reached chronic kidney disease stage 2 or better. Six-month patient and graft survival was 86%. There was one episode of graft rejection on belatacept therapy in a patient who had also had early rejection before initiation of belatacept. CONCLUSIONS: The results in this initial group of patients suggest that belatacept with mycophenolic acid may be a safe maintenance immunosuppression regimen in hepatitis C-positive liver transplant recipients with renal dysfunction, and that this regimen can serve as an effective bridge to calcineurin inhibitor therapy.