Liver Transplant Costs and Activity After United Network for Organ Sharing Allocation Policy Changes.

Importance: A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level. Objective: To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation. Design, Setting, and Participants: This cross-sectional study collected and reviewed LT volume from multiple centers across the US and cost data with attention to 8 specific center demographics. Two separate 12-month eras were compared, before and after the new UNOS allocation policy: March 4, 2019, to March 4, 2020, and March 5, 2020, to March 5, 2021. Data analysis was performed from May to December 2022. Main Outcomes and Measures: Center volume, changes in cost. Results: A total of 22 of 68 centers responded comparing 1948 LTs before the policy change and 1837 LTs postpolicy, resulting in a 6% volume decrease. Transplants using local donations after brain death decreased 54% (P < .001) while imported donations after brain death increased 133% (P = .003). Imported fly-outs and dry runs increased 163% (median, 19; range, 1-75, vs 50, range, 2-91; P = .009) and 33% (median, 3; range, 0-16, vs 7, range, 0-24; P = .02). Overall hospital costs increased 10.9% to a total of $46 360 176 (P = .94) for participating centers. There was a 77% fly-out cost increase postpolicy ($10 600 234; P = .03). On subanalysis, centers with decreased LT volume postpolicy observed higher overall hospital costs ($41 720 365; P = .048), and specifically, a 122% cost increase for liver imports ($6 508 480; P = .002). Transplant centers from low-income states showed a significant increase in hospital (12%) and import (94%) costs. Centers serving populations with larger proportions of racial and ethnic minority candidates and specifically Black candidates significantly increased costs by more than 90% for imported livers, fly-outs, and dry runs despite lower LT volume. Similarly, costs increased significantly (>100%) for fly-outs and dry runs in centers from worse-performing health systems. Conclusions and Relevance: Based on this large multicenter effort and contrary to current assumptions, the new liver distribution system appears to place a disproportionate burden on populations of the current LT community who already experience disparities in health care. The continuous allocation policies being promoted by UNOS could make the situation even worse.

Indications, Techniques, and Barriers for Pancreas Transplant Biopsy: A Consensus Perspective From a Survey of US Centers.

BACKGROUND: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described. METHODS: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies. RESULTS: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist's or biopsy performer's comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically. CONCLUSIONS: This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted.

Generating strategies for a national comeback in pancreas transplantation: A Delphi survey and US conference report.

In the United States, potential transplant candidates with insulin-dependent diabetes mellitus are inconsistently offered pancreas transplantation (PTx), contributing to a dramatic decline in pancreas allograft utilization over the past 2 decades. The American Society of Transplantation organized a workshop to identify barriers inhibiting PTx and to develop strategies for a national comeback. The 2-day workshop focused on 4 main topics: (1) referral/candidate selection, (2) organ recovery/utilization, (3) program performance/patient outcomes, and (4) enhanced education/research. Topics were explored through expert presentations, patient testimonials, breakout sessions, and strategic planning, including the identification of tasks for immediate focus. Additionally, a modified-Delphi survey was conducted among workshop members to develop and rate the importance of barriers, and the impact and feasibility of workgroup-identified improvement strategies. The panelists identified 16 barriers to progress and 44 strategies for consideration. The steps for a national comeback in PTx involve greater emphasis on efficient referral and candidate selection, better donor pancreas utilization practices, eliminating financial barriers to procurement and transplant, improving collaboration between transplant and diabetes societies and professionals, and increasing focus on PTx training, education, and research. Partnership between national societies, patient advocacy groups, and professionals will be essential to realizing this critical agenda.

Role of gastric peroral endoscopic myotomy (GPOEM) in chronic gastroparesis management after pancreas transplantation.

Gastroparesis is a common complaint among patients with diabetes. Symptoms tend to improve following successful pancreas transplantation (PTx), but persist despite euglycemia in a subset of patients. We aimed to assess the benefit of gastric peroral endoscopic myotomy (G-POEM) in persistent gastroparesis following PTx. This was a single center retrospective review of all patients who underwent G-POEM for persistent gastroparesis following PTx. Patient demographics, pre and post procedure perception of symptom severity according to the patient assessment of upper gastrointestinal symptoms severity index (PAGI-SYM), gastroparesis cardinal symptom index (GCSI) score, and 36-item short form survey (SF36) score along with gastric emptying scintigraphy (GES) were analyzed. Seven PTx recipients underwent G-POEM for persistent gastroparesis symptoms. The majority were female. All reported nausea/vomiting, abdominal pain, bloating, and post prandial fullness prior to G-POEM. The post procedure survey scores improved in all patients although this was not significant. The improvement in gastric emptying on GES was statistically significant. G-POEM is a relatively new treatment option for gastroparesis. While it requires specialized proceduralist and training, we have documented improvement in the management of symptoms. With increasing experience, we anticipate more significant benefit in post PTx patients with persistent symptoms of gastroparesis undergoing G-POEM.

Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study.

Pancreas transplantation alone (PTA) is a ß cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

Epidemiology and Risk Factors for Invasive Fungal Infections in Pancreas Transplant in the Absence of Postoperative Antifungal Prophylaxis.

Background: Invasive fungal infections (IFIs) remain a rare yet dreaded complication following pancreas transplantation. Current guidelines recommend antifungal prophylaxis in patients with 1 or more risk factors. At our center, single-dose antifungal prophylaxis is administered in the operating room but none subsequently, regardless of risk factors. Here we evaluate the 1-year incidence, outcome, and risk factors associated with IFI following pancreas transplantation. Methods: A retrospective, single-center cohort study was conducted in patients who underwent pancreas transplantation between 1 January 2009 and 31 December 2019. Records were manually reviewed, and cases were adjudicated using consensus definitions. The 1-year cumulative incidence, mortality, and risk factors were analyzed by Kaplan-Meier method and differences between populations were assessed with Fisher test and Mann-Whitney U test. Results: Three hundred sixty-nine recipients were included. Twelve IFIs were identified: candidiasis (8), aspergillosis (2), histoplasmosis (1), and cryptococcosis (1). Intra-abdominal infections were the most common presentation (5), followed by bloodstream infections (3), disseminated disease (2), pulmonary disease (1), and invasive fungal sinusitis (1). Median time to IFI was 64 days (interquartile range, 30-234 days). One-year cumulative incidence was 3.25% (95% confidence interval, 1.86%-5.65%). There were no significant differences between patients with or without IFI regarding type of transplant (P = .17), posttransplant dialysis (P = .3), rejection (P = .5), cytomegalovirus serostatus (P = .45), or reoperation (P = .19). For patients with IFI, the 1-year graft and patient survival rates were 58% versus 95% (P < .0001) and 75% versus 98.6% (P < .001), respectively. Conclusions: Our study suggests that the use of a single-dose antifungal prophylaxis administered in the operating room but none subsequently does not result in an increased incidence of IFI following pancreas transplantation.

Revitalizing pancreas transplantation: creation of a hands-on training course for pancreas allograft procurement, backbench preparation, and transplantation.

Despite a steady increase in the number of organs available for transplant in the United States, over the last two decades there has been a precipitous decrease in the annual number of pancreas transplants performed. One overlooked consequence of this decline in pancreas transplant volume has been a decrease in experience in proper pancreas procurement and transplantation techniques for transplant surgeons as well as fewer trained abdominal transplant fellows entering the workforce certified for pancreas procurement and transplantation, with those achieving certification having less-developed judgment, skills, and experience. To augment current fellowship training and provide a concentrated experience in pancreas procurement and transplantation, the ASTS developed a hands-on surgical skills workshop focused on proper techniques for pancreas allograft procurement and backbench preparation.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. METHODS: All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. RESULTS: Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. CONCLUSIONS: Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

Impact of gut microbiota on liver transplantation.

The gut microbiota has been gaining attention due to its interactions with the human body and its role in pathophysiological processes. One of the main interactions is the "gut-liver axis," in which disruption of the gut mucosal barrier seen in portal hypertension and liver disease can influence liver allograft function over time. For example, in patients who are undergoing liver transplantation, preexisting dysbiosis, perioperative antibiotic use, surgical stress, and immunosuppressive use have each been associated with alterations in gut microbiota, potentially impacting overall morbidity and mortality. In this review, studies exploring gut microbiota changes in patients undergoing liver transplantation are reviewed, including both human and experimental animal studies. Common themes include an increase in Enterobacteriaceae and Enterococcaceae species and a decrease in Faecalibacterium prausnitzii and Bacteriodes, while a decrease in the overall diversity of gut microbiota after liver transplantation.

Modern indications for referral for kidney and pancreas transplantation.

PURPOSE OF REVIEW: Pancreas transplantation (PTx) is currently the only therapy that can predictably achieve sustained euglycemia independent of exogenous insulin administration in patients with insulin-dependent diabetes mellitus. This procedure involves a complex abdominal operation and lifetime dependence on immunosuppressive medications. Therefore, PTx is most frequently performed in combination with other organs, usually a kidney transplant for end stage diabetic nephropathy. Less frequently, solitary PTx may be indicated in patients with potentially life-threatening complications of diabetes mellitus. There remains confusion and misperceptions regarding indications and timing of patient referral for PTx. RECENT FINDINGS: In this review, the referral, evaluation, and listing process for PTx is described, including a detailed discussion of candidate assessment, indications, contraindications, and outcomes. SUMMARY: Because the progression of diabetic kidney disease may be less predictable than other forms of kidney failure, early referral for planning of renal and/or pancreas transplantation is paramount to optimize patient care and allow for possible preemptive transplantation.

Pancreas Transplantation: Current Challenges, Considerations, and Controversies.

Pancreas transplantation (PTx) reestablishes an autoregulating source of endogenous insulin responsive to normal feedback controls. In addition to achieving complete ß-cell replacement that frees the patient with diabetes from the need to monitor serum glucose and administer exogenous insulin, successful PTx provides counterregulatory hormone secretion and exocrine function. A functioning PTx mitigates glycemic variability, eliminates the daily stigma and burden of diabetes, restores normal glucose homeostasis in patients with complicated diabetes, and improves quality of life and life expectancy. The tradeoff is that it entails a major surgical procedure and requisite long-term immunosuppression. Despite the high likelihood of rendering patients euglycemic independent of exogenous insulin, PTx is considered a treatment rather than a cure. In spite of steadily improving outcomes in each successive era coupled with expansion of recipient selection criteria to include patients with a type 2 diabetes phenotype, a decline in PTx activity has occurred in the new millennium related to a number of factors including: (1) lack of a primary referral source and general acceptance by the diabetes care community; (2) absence of consensus criteria; and (3) access, education, and resource issues within the transplant community. In the author's experience, patients who present as potential candidates for PTx have felt as though they needed to circumvent the conventional diabetes care model to gain access to transplant options. PTx should be featured more prominently in the management algorithms for patients with insulin requiring diabetes who are failing exogenous insulin therapy or experiencing progressive diabetic complications regardless of diabetes type. Furthermore, all patients with diabetes and chronic kidney disease should undergo consideration for simultaneous pancreas-kidney transplantation independent of geography or location.

Vasopressin for Post-kidney Transplant Hypotension.

Introduction: Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods: Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results: Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion: Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.

Clinical Aspect of Cytokines and Chemokines in Liver Transplant.

BACKGROUND: The objective of this prospective observational study was to determine whether a transplanted liver graft releases proinflammatory cytokines and chemokines on reperfusion and to determine the relationship between these molecules and subsequent ischemic reperfusion injury and acute kidney injury. METHODS: Blood samples from 66 consecutive patients undergoing liver transplant were analyzed for cyto- and chemokines at different time frames before and after liver transplant. Ischemic reperfusion injury was defined based on the peak levels of arginine transaminase and divided into 3 groups: mild, moderate, and severe. Acute kidney injury was defined according to the latest Kidney Disease: Improving Global Outcomes classification. RESULTS: For more than 40 different cyto/chemokines and growth factors, a certain pattern of expression was observed in all patients with ischemic reperfusion injury. G-SCF, IP10, and HSP90a were significantly elevated in all patients with ischemic reperfusion injury. On the other hand, eotaxin and MCP1 levels were markedly elevated in patients without ischemic reperfusion, suggesting a possible cytoprotective effect. We identified cold ischemia, macrosteatosis > 30%, postreperfusion syndrome, and postoperative use of 2 or more vasoactive agents as independent risk factors for ischemic reperfusion injury. CONCLUSIONS: Ischemia reperfusion injury is accompanied by distinct innate and adaptive immune cytokine signatures before and after transplant. It can be used for therapeutic intervention with goal to improve post-transplant graft outcomes.

Analyzing outcomes following pancreas transplantation: Definition of a failure or failure of a definition.

Pancreas transplantation has an identity crisis and is at a crossroads. Although outcomes continue to improve in each successive era, the number of pancreas transplants performed annually in the United States has been static for several years in spite of increasing numbers of deceased donors. For most practitioners who manage diabetes, pancreas transplantation is considered an extreme measure to control diabetes. With expanded recipient selection (primarily simultaneous pancreas-kidney transplantation) in patients who are older, have a higher BMI, are minorities, or who have a type 2 diabetes phenotype, the controversy regarding type of diabetes detracts from the success of intervention. The absence of a clear and precise definition of pancreas graft failure, particularly one that lacks a measure of glycemic control, inhibits wider application of pancreas transplantation with respect to reporting long-term outcomes, comparing this treatment to alternative therapies, developing listing and allocation policy, and having a better understanding of the patient perspective. It has been suggested that the definition of pancreas graft failure should differ depending on the type of pretransplant diabetes. In this commentary, we discuss current challenges regarding the development of a uniform definition of pancreas graft failure and propose a potential solution to this vexing problem.

Impact of race on pancreas transplant outcomes in the current era: It is not all Black and White.

The growth in pancreas transplant is driven in part by expansion of indications to include an increasing number of select patients with type 2 diabetes. Two papers in this month's issue of Clinical transplantation specifically investigate this association, and in parallel illustrate the complexity of defining the association of race with pancreas transplant outcomes from different perspectives and illustrate several important concepts related to health equity in organ transplantation.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.