The history of ethical principles in liver transplant organ allocation in the United States: how historical and proposed allocations system fare in balancing utility vs. urgency and justice vs. pragmatism.

PURPOSE OF REVIEW: The United States (US) liver transplant community is processing changes to the allocation system and developing a new proposal that will result in even greater change. This review evaluates the ethical implications of these decisions, focusing on two sets of competing ethical principles (Urgency vs. Utility and Justice vs. Pragmatism). RECENT FINDINGS: About four years ago, the Organ Procurement and Transplantation Network (OPTN) implemented the Acuity Circle Model to replace the geographic boundaries of organ procurement organizations (OPOs). Here, we review how effectively this model reduced regional variation in access and improved waitlist survival. Likewise, the OPTN is planning to transition to a continuous distribution model which will redefine the scoring systems for allocation. We will discuss how the ethical priorities discussed above should be considered while developing the new system. SUMMARY: Every change in organ allocation policy must balance competing ethical imperatives. Although our community's emphasis on urgency over utility is appropriate, we should study the potential benefits of considering utility in the system. Meanwhile, our push for more Justice in the system should remain our imperative and Pragmatism should only be considered to minimize the costs of these changes.

Arterial Anastomosis Using Microsurgical Techniques in Adult Live Donor Liver Transplant: A Focus on Technique and Outcomes at a Single Institution.

BACKGROUND: Microvascular hepatic artery reconstruction (MHAR) is associated with decreased rates of hepatic artery thrombosis (HAT) in living donor liver transplantation (LDLT). There is a paucity of literature describing the learning points and initiation of this technique at the institutional level. The objective of this study is to report our institutional experience using MHAR in adult LDLT with a focus on technique and outcomes. METHODS: A retrospective review of adult patients who underwent LDLT from January 2012 to December 2020 was conducted. Patients were divided into two groups, those who underwent LDLT without MHAR and with MHAR. We analyzed cases for technical data including donor and recipient artery characteristics, anastomotic techniques, intraop events, and postop complications. A Mann-Whitney test was performed to compare outcomes between non-MHAR and MHAR patients. RESULTS: Fifty non-MHAR and 50 MHAR patients met inclusion criteria. Median age at transplantation was 58 (interquartile range [IQR] 11.8) and 57.5 years (IQR 14.5), respectively. Median follow-up for MHAR patients was 12.8 months (IQR 11.6). The most common recipient arteries were the right hepatic artery (HA) (58%) and left HA (20%). Median size of recipient and donor arteries were 3.3 mm (IQR 0.7) and 3.1 mm (IQR 0.7), resulting in a median mismatch size of 0.3 mm (IQR 0.4). Median microanastomosis time was 44 minutes (IQR 0). HAT, graft failure, and mortality rates were higher in the non-MHAR cohort (6% vs. 0%, 8% vs. 0%, and 16% vs. 6%, respectively); however, these did not reach statistical significance. CONCLUSION: This study found lower rates of HAT and graft failure after implementing MHAR, though statistical significance was not achieved. Larger cohort studies are needed to further assess the potential benefit of MHAR in adult LDLT. From our experience, MHAR requires cooperation between the transplant and microsurgical teams, with technical challenges overcome with appropriate instrumentation and planning.

Long-Term Suitability of Left Gastric Artery Inflow for Arterial Perfusion of Living Donor Right Lobe Grafts.

Poorer than expected, living donor liver transplant outcomes are observed after recipient graft artery thrombosis. At grafting, the risk for later thrombosis is high if a dissected hepatic artery is used for standard reconstruction. Surgeon diagnosis of dissection requires nonstandard management with alternative technique in addition to microvascular expertise. Intimal flap repair with standard reconstruction is contingent on basis of a redo anastomosis. It is a suboptimal choice for living donor transplantation. Achieving goal graft arterial perfusion at first revascularization is crucial for superior outcomes. Managing dissection at grafting with nonstandard left gastric artery reconstruction is unreported. Our experience is limited, but this is our preferred alternative technique to standard hepatic artery reconstruction complicated by dissection. Here, we describe our two-case experience with left gastric arterialized grafts for management of dissection. Our living donor graft recipients with alternatively arterialized grafts are now 6- and 2-years posttransplant.

A Programmatic Response, Including Bamlanivimab or Casirivimab-imdevimab Administration, Reduces Hospitalization and Death in COVID-19 Positive Abdominal Transplant Recipients.

BACKGROUND: (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant recipients. In December 2020, at the peak of the Los Angeles outbreak, our center rapidly implemented a protocol to improve outpatient management and provide bamlanivimab or casirivimab-imdevimab [COVID monoclonal antibody (mAb) therapies] to all eligible COVID-19 positive liver and kidney transplant recipients. METHODS: A retrospective review of all abdominal organ transplant recipients who were COVID-19 polymerase chain reaction positive between February 2020 and February 2021 from our center was performed. Patient demographics, COVID-19 treatments, hospitalizations, and survival were reviewed. Patients were considered eligible for COVID mAb therapy if they met outpatient criteria at the time of diagnosis. RESULTS: In the study period, 121 patients in the kidney transplant recipients group (KG) and 105 patients in the liver or combined liver/kidney transplant recipients group (LG) were COVID-19 polymerase chain reaction positive. Hospitalization rates were similar for the KG (45%) versus LG (35%) (P = 0.20), but mortality was higher for the KG (22%) when compared to LG (10%) (P = 0.02). Our programmatic response, including outpatient COVID mAb therapies, reduced hospitalizations (P = 0.01) and deaths (P = 0.01). Ninety-four KG and 87 LG patients were identified as potentially eligible for COVID mAb therapy, and 17 KG and 17 LG patients were treated. COVID mAb therapies reduced hospitalization from 32% to 15% (P = 0.045) and eliminated mortality (13% versus 0%, P = 0.04). CONCLUSIONS: An aggressive approach including outpatient COVID mAb therapy in the COVID positive abdominal organ transplant recipients significantly decreased hospitalization and death. Early outpatient intervention for COVID-19 disease in transplant patients should be considered where possible.

Transfusion-free Retransplantation for Post-liver Transplantation Hepatic Artery Thrombosis: How Much Augmentation Is Too Much?

Liver transplantation presents unique challenges in patients who do not accept blood transfusions. The difficulty of balancing chemical augmentation and handling the technical difficulty of the surgery make transfusion-free liver transplantation an exception rather than the norm. However, at our center, we have performed 27 successful living donor liver transplants in transfusion-free patients. We describe a case of hepatic artery thrombosis (HAT) after living donor liver transplantation requiring retransplantation. This first report of safe retransplantation without blood products demonstrates that even graft-threatening complications can be safely managed in a transfusion-free setting. However, it remains unclear if the medical augmentation to meet hematologic and coagulation parameters before transfusion-free transplantation may increase the risk of postoperative HAT and other thrombotic complications. Although it is our center's experience that the thrombosis rate is comparable with the published rate in standard transfusion-eligible living donor liver transplantations and this case demonstrates that HAT can be safely managed in this setting, further study on the risks and benefits of hematopoietic stimulants as pretransplant optimization is warranted.

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation.

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81-0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.

Biliary Internal Stents and Biliary Complications in Adult Liver Transplantation.

BACKGROUND: Biliary complications in liver transplantation (LT) can cause significant morbidity or even lead to a potential graft loss and patient mortality. Oftentimes biliary internal stents (ISs) are used at the time of LT to lower the risk for or prevent these biliary complications; however, their efficacy and outcomes remain controversial. METHODS: A retrospective cohort study was conducted on all of the adult patients who underwent a deceased-donor LT (DDLT) with an end-to-end choledococholedocostomy. An IS was placed across the biliary anastomosis, passing through the ampulla. We compared the demographic profiles and various outcomes between the 2 groups (no-IS group vs IS group) and examined risk factors associated with anastomotic biliary complications. RESULTS: The study comprised 350 patients in the no-IS group and 132 patients in the IS group. Anastomotic biliary fistula (ABF) occurred in 5 (1.4%) and 1 (0.8%) patients in the no-IS group and the IS group, respectively (P = .55). Anastomotic biliary stricture (ABS) occurred in 53 (15.1%) and 18 (13.6%) patients, respectively (P = .68). No significant difference was found in the overall biliary complications between the 2 groups (P = .33). In multivariate logistic regression analysis, acute rejection was the only risk factor for ABS (P = .02). One biliary complication-induced mortality occurred in the no-IS group in which the patient died of an ABF-induced hepatic artery pseudoaneurysm rupture. CONCLUSION: The use of biliary ISs in DDLT did not reduce the overall risk for biliary complications, but more research is needed to draw definite conclusions.

A Potential Role for Robotic Cholecystectomy in Patients with Advanced Liver Disease: Analysis of the NSQIP Database.

Robotic surgery has been widely adopted by many specialties, including hepatobiliary surgery. However, robotic procedures generally require longer operative times and are costlier than their laparoscopic counterparts. The role for robotic cholecystectomy (RC), particularly in patients with advanced liver disease, has not been established. A retrospective analysis of the NSQIP database was performed, focusing on patients with chronic liver disease who underwent cholecystectomy. Patients were categorized based on their model for end-stage liver disease (MELD) score and the type of surgical procedure: open, laparoscopic, or RC. Rates of a variety of postoperative complications including length of stay (LOS) were analyzed. In patients with a MELD score of 21 to 30, open cholecystectomy was associated with a long hospital LOS (3 vs 1 vs 1; P -0.01). RC was equivalent to laparoscopic cholecystectomy in terms of perioperative mortality for higher MELD score patients but was associated with lower conversion rates and overall LOS. This data suggests that RC should be considered in patients with advanced liver disease needing cholecystectomy.

Striving for more just allocation of liver allografts between patients with and without hepatocellular carcinoma: successes and challenges.

PURPOSE OF REVIEW: Recently the United Network for Organ Sharing (UNOS) adopted new rules for the allocation of liver allografts for recipients with hepatocellular carcinoma (HCC) in hopes of removing regional variation in HCC practice and regional differences in patient survival. Understanding how previous changes to HCC allocation have both succeeded and failed to match the pretransplant mortality of HCC and non-HCC patients on the waitlist will help us to better evaluate these changes and predict where we may again fail. RECENT FINDINGS: Previous revisions of the HCC allocation rules were successful in more accurately matching the waitlist mortality of HCC and non-HCC patients. Efforts to select for less aggressive tumor biology have resulted in better disease free and patient survival. Several articles have also supported the practice of using locoregional therapies to downstage the patients to within Milan criteria. New rules seek to reduce the amount of geographic disparity in the allocation system. SUMMARY: Over time UNOS has steady improved the liver allocation polices to attempt to match pretransplant mortality for patients with HCC and without HCC. The latest changes to the organ allocation rules succeed in implementing some of these best practices. However, one can also predict several ongoing challenges to fair allocation that may not have been addressed by recent changes.

Successful Renal Transplantation after Presumed Cyanide Toxicity Treated with Hydroxocobalamin and Review of the Literature.

We report two cases of successful renal transplantation with allografts from donors who suffered anoxic brain injury as the primary cause of death from house fires. Each was treated prophylactically with hydroxocobalamin (Cyanokit) for suspected cyanide toxicity. During organ procurement, gross examination was notable for deep discoloration of the parenchymal tissues. Approximately 6 and 18 months after transplantation, both recipients have excellent renal graft function and remain independent from hemodialysis (HD). Hydroxocobalamin is the antidote for suspected acute cyanide toxicity. While largely tolerated by the recipient, there is concern over the potential functional implications of the associated side effects of dramatic tissue discoloration and development of oxalate crystals. Furthermore, difficulties performing hemodialysis in patients treated with hydroxocobalamin have been reported due to discoloration of the effluent fluid impacting the colorimetric sensor, causing false alarms and repetitive interruptions. As such, many transplant centers in the United States (US) continue to reject these organs. We seek to highlight two cases of successful transplantation following donor administration of hydroxocobalamin (Cyanokit) and present the first documented case of successful perioperative intermittent hemodialysis following transplantation of an allograft exposed to hydroxocobalamin. Furthermore, we emphasize the importance of optimal organ utilization and caution against unnecessary refusal.

Islet transplantation for Type 1 diabetes: where are we now?

Pancreatic islet transplantation is a minimally invasive procedure that can restore normoglycemia and insulin independence in Type 1 diabetics without the surgical complications associated with vascularized pancreas transplantation. The advances made in this field over the past decade have dramatically improved patient outcomes, and the procedure is now transitioning from an experimental treatment to a clinical reality. Nonetheless, a number of important issues continue to hamper the success of islet transplantation and must be addressed before there is widespread clinical acceptance. These include the relative inefficiency of the islet isolation process, the progressive loss of islet function over time and the need for multiple donors to achieve insulin independence. Here, we discuss the current status of islet transplantation and examine its future as a treatment for Type 1 diabetes.

Experience with laparoscopic donor nephrectomy among more than 1000 cases: low complication rates, despite more challenging cases.

HYPOTHESIS: Despite the overall acceptance of laparoscopic donor nephrectomy (LDNX), concern remains about the application of this technique in certain complex situations, such as right-sided nephrectomies and in donors with complex kidney anatomy and obese donors. This study was designed to determine if complication rates have remained stable as we have offered LDNX to all medically acceptable donors and to analyze the results of cases in each of the complex categories. We hypothesized that complication rates in the 3 complex categories would be equivalent to those among more straightforward cases. DESIGN: Retrospective medical record review. SETTING: Academic medical center. PATIENTS: A total of 1045 patients who underwent LDNX between November 3, 1999, and August 28, 2009. MAIN OUTCOMES MEASURES: Operative times, lengths of hospital stay, overall complications, major complications, conversions to open surgery, blood transfusions, readmissions, and reoperations. RESULTS: The outcomes of the first 250 patients (when LDNX was selectively offered) were compared with the outcomes of the last 795 patients (when LDNX was offered to all medically acceptable donors). Overall operative times significantly improved (212 vs 176 minutes), overall complication rates did not change (6.4% vs 5.5%), and major complication rates significantly declined (4.0% vs 1.4%). Among the last 795 patients, 1 conversion to open surgery and 1 blood transfusion occurred. There were no deaths in the series. Moreover, no differences in overall or major complication rates were seen when cases involving 200 right-sided nephrectomies, 204 donors with complex kidney anatomy, and 148 obese donors were analyzed independently. CONCLUSIONS: Low complication rates persist for LDNX, even when applied to more technically challenging cases. This procedure is offered to all medically acceptable donors, with an excellent safety profile, and should be considered the standard of care for kidney donation.

HIV-1 transgenic rats develop T cell abnormalities.

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4+ and CD8+ T cells able to produce IFN-gamma following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4+ and CD8+ effector/memory (CD45RC- CD62L-) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naïve (CD45RC+ CD62L+) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process.