Effects of major liver allocation policy changes on waitlist outcomes in multivisceral transplantation in the United States

Background: Organ allocation in multivisceral transplant (MVT; liver-intestine, liver-pancreas-intestine) is determined based on their ranking in the liver transplant waitlist. MVT candidates do not usually have high laboratory MELDNa (MELD) score and an exception point is given per the OPTN policy. Currently, their exception point is determined as 10% increase in mortality risk to their MELD score. Since 2013, an exception point of 29 has been applied to MVT candidates with approval by regional review board. As major revisions in liver allocation, Share 35 rule and MELDNa score were implemented in 2013 and 2016. The aim of this study was to evaluate effects of these updates in liver allocation policy on waitlist outcomes in MVT. Methods: We examined adult patients who were registered for liver alone (LTA), liver-kidney (L-K), and MVT between 2011 and 2018 by using the UNOS registry. Registration periods were grouped according to the major revisions of liver allocation; 1) pre-Share 35 period (1/1/2011-6/17/2013), 2) post- Share 35 period (6/18/2013-1/10/2016), 3) MELDNa period (1/11/2016- 3/31/2018). 90-day waitlist mortality in MVT candidates were evaluated in each period in comparison with those in LTA/L-K candidates who had similar MELD score (score categories of 20-28 and 29-34) to exception points for MVT candidates. Risks were adjusted by using Fine-Gray regression model. Results: In MVT candidates, while there was no difference between the pre and post-Share 35 periods (HR, 0.96; P=0.29), 90 day-mortality significantly increased in the MELDNa period compared with that in post-Share 35 period (HR, 1.08; P=0.02). Mortality within 90 days in LTA/L-K candidates with MELD score of 20-28 continued to decrease over periods (hazard ratio [HR], 0.91 and 0.82; P=0.042 and \u3c0.001 for pre vs. post-Share 35 periods and post-Share 35 vs. MELDNa periods). 90 day-mortality in LTA/L-K candidates with MELD score of 29-34 significantly decreased in the MELDNa period compared with the post-Share 35 period (HR, 0.78; P\u3c0.001), whereas there was no difference between the pre and post-Share 35 periods (HR, 0.99; P=0.9). Conclusions: While the recent revisions of liver allocation improved waitlist outcomes in LTA/L-K candidates, MVT candidates did not benefit from them and 90 day-mortality significantly increased in the MELDNa period. Exception point for MVT candidates may need to be reconsidered, given the increased number of high score patients

Effects of Major Liver Allocation Policy Changes on Waitlist Outcomes in Multivisceral Transplantation

Purpose: Liver-intestine allocation is determined in the liver waitlist. This study aimed to evaluate effects of recent updates in liver allocation policy on waitlist outcomes in liver-intestine (multivisecral) transplant (MVT). Methods: We examined adult patients who were registered for liver-alone/liver-kidney transplant (LTA/LKT), and MVT between 2011 and 2018 by using the UNOS registry. Registration periods were grouped according to the recent revisions of liver allocation; pre-Share 35 (1/1/2011-6/17/2013), post-Share 35 (6/18/2013-1/10/2016). and MELDNa (1/11/2016-3/31/2018). 90-day waitlist mortality in MVT and LTA/LKT candidates were evaluated and effects of allocation changes were compared. Results: The number of LTA/LKT candidates listed with score of \u3e29 significantly increased over penods (128, 149, and 189/month in pre-Share 35, post-Share 35. and MELDNa periods, respectively; PO. 001). A risk of 90 day-waitlist mortality in LTA/LKT candidates with MELD score of 20-28 decreased over periods (hazard ratio [HR], 0. 91 and 0. 82; P-0. 042 and \u3c0. 001 for pre vs. post-Share 35 and post-Share 35 vs. MELDNa). In those with score of 29-34, a risk of 90-day morality significantly decreased in the MELDNa period (HR, 0. 78; PO. 001 [ref post-Share 35]). In MVT candidates, while no difference in 90-day mortality between pre and post-Share 35 (HR, 0. 96; PO. 29), it significantly increased in the MELDNa period (HR, 1. 08; P-0. 02 [ref. post-Share 35]). Conclusions: Exception score for MVT candidates may need to be reconsidered. given the adverse impact of MELDNa based allocation which might be associated with the increasing number of high score patients

Effects of Major Liver Allocation Policy Changes on Waitlist Outcomes in Multivisceral Transplantation

Purpose: Liver-intestine allocation is determined in the liver waitlist. This study aimed to evaluate effects of recent updates in liver allocation policy on waitlist outcomes in liver-intestine (multivisecral) transplant (MVT). Methods: We examined adult patients who were registered for liver-alone/liver-kidney transplant (LTA/LKT), and MVT between 2011 and 2018 by using the UNOS registry. Registration periods were grouped according to the recent revisions of liver allocation; pre-Share 35 (1/1/2011-6/17/2013), post-Share 35 (6/18/2013-1/10/2016). and MELDNa (1/11/2016-3/31/2018). 90-day waitlist mortality in MVT and LTA/LKT candidates were evaluated and effects of allocation changes were compared. Results: The number of LTA/LKT candidates listed with score of \u3e29 significantly increased over penods (128, 149, and 189/month in pre-Share 35, post-Share 35. and MELDNa periods, respectively; PO. 001). A risk of 90 day-waitlist mortality in LTA/LKT candidates with MELD score of 20-28 decreased over periods (hazard ratio [HR], 0. 91 and 0. 82; P-0. 042 and \u3c0. 001 for pre vs. post-Share 35 and post-Share 35 vs. MELDNa). In those with score of 29-34, a risk of 90-day morality significantly decreased in the MELDNa period (HR, 0. 78; PO. 001 [ref post-Share 35]). In MVT candidates, while no difference in 90-day mortality between pre and post-Share 35 (HR, 0. 96; PO. 29), it significantly increased in the MELDNa period (HR, 1. 08; P-0. 02 [ref. post-Share 35]). Conclusions: Exception score for MVT candidates may need to be reconsidered. given the adverse impact of MELDNa based allocation which might be associated with the increasing number of high score patients

Comparison of induction and maintenance immunosuppression regimens in intestinal and multivisceral transplantation: An analysis of the unos registry.

Aim: Induction and maintenance immunosuppression regimens in intestinal transplant widely vary among centers. The aim of this study was to investigate an association between immunosuppression regimens and transplant outcomes. Methods: We examined adult and pediatric patients who underwent primary intestinal/multivisceral transplant between January 1, 2001 and March 31, 2017 by using the United Network Organ Sharing registry. Intestine transplant without liver graft group and intestine and liver transplant group were separately analyzed. Patients were categorized based on immunosuppression regimens. Induction regimen groups included none, anti-thymocyte globulin (ATG) with or without rituximab, basiliximab, and alemtuzumab. Additional maintenance agent groups included none, mycophenolic acid, and sirolimus/everlolimus (mTOR-i). Graft and patient survival, death associated with infection, and incidence of acute rejection were evaluated using Cox and logistic multivariable analyses. Risks were adjusted for recipient age/ethnicity/functional status, donor age, and ischemia time. Results: A total of 1676 patients were eligible for this study (intestine without liver [n=780], intestine with liver [n=896]). In the intestine without liver group, alemtuzumab (hazard ratio [HR]=0.56, P=0.012) and mTOR-i (HR=0.62, P=0.026) showed significantly better graft survival, compared with ATG+rituximab and no additional maintenance agent, respectively. In the intestine with liver group, there was no induction regimen superior to others regarding graft/patient survival, whereas a risk of death associated with infection was lowest in the ATG+rituximab group and highest in the alemtuzumab group (HR=3.324, P=0.034). The mTOR-i group showed significantly better graft outcome in intestine and liver transplant (HR=0.476, P=0.003 [Ref. no additional maintenance agent]). A risk of acute rejection was significantly lower in the ATG+rituximab group, compared with the groups of ATG alone or almtuzumab, regardless of a graft type. Conclusion: Our results suggested that alemtuzumab induction with mTOR-i as an additional maintenance agent seemed appropriate in intestinal transplant without liver graft, and that ATG+rituximab induction with mTOR-i may be a better option in intestinal transplant with liver graft

Safety and efficacy of mTOR inhibitors following intestine and multivisceral transplantation

Purpose: Review the indications, outcomes and frequency of the use of mTOR inhibitors (mTORs) after intestine (IT) and multivisceral transplantation (MVT) assessed across two transplant centers in the United States. Methods: We evaluated patients receiving everolimus or sirolimus following MVT or IT and compiled retrospective data between 2009-2018 at multiple transplant centers. Results: 22 patients received immunosuppression including an mTOR. Twenty patients were over 18 years. Twelve patients received isolated IT. The most common reason for transplant was short gut syndrome (45%) followed by dysmotility (22%) and neuroendocrine tumor (18%). Mean age at transplant was 46 years (range 22 - 62) in adults and 2.5 in children. 54% patients were started on mTORs beyond 1 year post transplant. Mean time from transplant to initiation of mTOR was 24 months (range 1 - 78). 63.6% received sirolimus and 36.4% received everolimus. Other medications at the time of mTORs initiation included tacrolimus, prednisone, mycophenolate mofetil (MMF) and azathioprine. 18%, 13.6% and 59% of patients on mTORs were able to discontinue MMF, prednisone or reduce tacrolimus respectively. Only one patient was weaned to mTOR as single immunosuppression agent. Reason for mTOR use was renal dysfunction in 59% of cases; of these, only one patient had chronic kidney disease pre transplant. Mean glomerular filtration rate (GFR) prior to mTORs initiation was 40mL/min/1.73sqm. Of those placed on mTORs for renal insufficiency 69.2% had substantial improvement in GFR (defined as increase of 10 points). Nine patients developed some worsening of proteinuria but none were taken off treatment due to this. 27.3% cases developed acute cellular rejection (ACR), 13.6% had cytomegalovirus and two patients died while being on mTOR therapy. mTORs were discontinued in 11/22 cases due to side effects (54.5%), surgeries (18.1%) or ACR (9%). Sirolimus was discontinued in 8/14 (57%), everolimus was discontinued in 3/8 (37.5%). The mean duration of mTORs use in those stopping therapy was 7 months and 18 months in those remaining on therapy. Conclusion: Tolerance of therapy remains challenging with almost a third of those started on mTors unable to tolerate long term treatment due to side effects. If well tolerated, mTORs were generally safe and efficacious following IT and MVT. Further studies with a control group are warranted

Safety and efficacy of mTOR inhibitors following intestine and multivisceral transplantation

Purpose: Review the indications, outcomes and frequency of the use of mTOR inhibitors (mTORs) after intestine (IT) and multivisceral transplantation (MVT) assessed across two transplant centers in the United States. Methods: We evaluated patients receiving everolimus or sirolimus following MVT or IT and compiled retrospective data between 2009-2018 at multiple transplant centers. Results: 22 patients received immunosuppression including an mTOR. Twenty patients were over 18 years. Twelve patients received isolated IT. The most common reason for transplant was short gut syndrome (45%) followed by dysmotility (22%) and neuroendocrine tumor (18%). Mean age at transplant was 46 years (range 22 - 62) in adults and 2.5 in children. 54% patients were started on mTORs beyond 1 year post transplant. Mean time from transplant to initiation of mTOR was 24 months (range 1 - 78). 63.6% received sirolimus and 36.4% received everolimus. Other medications at the time of mTORs initiation included tacrolimus, prednisone, mycophenolate mofetil (MMF) and azathioprine. 18%, 13.6% and 59% of patients on mTORs were able to discontinue MMF, prednisone or reduce tacrolimus respectively. Only one patient was weaned to mTOR as single immunosuppression agent. Reason for mTOR use was renal dysfunction in 59% of cases; of these, only one patient had chronic kidney disease pre transplant. Mean glomerular filtration rate (GFR) prior to mTORs initiation was 40mL/min/1.73sqm. Of those placed on mTORs for renal insufficiency 69.2% had substantial improvement in GFR (defined as increase of 10 points). Nine patients developed some worsening of proteinuria but none were taken off treatment due to this. 27.3% cases developed acute cellular rejection (ACR), 13.6% had cytomegalovirus and two patients died while being on mTOR therapy. mTORs were discontinued in 11/22 cases due to side effects (54.5%), surgeries (18.1%) or ACR (9%). Sirolimus was discontinued in 8/14 (57%), everolimus was discontinued in 3/8 (37.5%). The mean duration of mTORs use in those stopping therapy was 7 months and 18 months in those remaining on therapy. Conclusion: Tolerance of therapy remains challenging with almost a third of those started on mTors unable to tolerate long term treatment due to side effects. If well tolerated, mTORs were generally safe and efficacious following IT and MVT. Further studies with a control group are warranted

An assessment of psychiatric needs pre-and postmultivisceral transplant

Introduction: As intestinal transplant becomes a more viable treatment option, there has been increased interest in quality of life and other psychosocial metrics. Systematic review suggests that quality of life improves post-transplant. However, there is limited data regarding psychosocial issues present at initial evaluation and post-transplant. Given that psychiatric issues are associated with increased mortality in solid organ transplant, this study aims to highlight psychosocial patterns that are present at initial evaluation and post-transplant. Methods: This study was a retrospective chart review of 28 patients who received intestinal transplants between 8/3/10-1/3/17 at an academic hospital in the United States. Psychosocial variables from encounters with health psychology senior staff and trainees were extracted. Descriptive data were evaluated from pre and post-transplant encounters. Results: Pre-transplant, the most common initial diagnosis was adjustment disorder (68%) with more significant pathology occurring in the remaining patients. 3/28 patients had comorbid substance use issues. 12/28 patients were on psychotropic medications during initial evaluation with 50% of those on multiple medications. Figure 1 describes data from initial psychological assessment. Of those eventually transplanted, 8 required further intervention prior to psychosocial clearance. Among the 28 patients, psychology was consulted an average of 2.71 times. Of those that required follow-up, there was an average of 8.25 follow-ups. Most common reasons for consult were; depression, pain, anxiety, eating related issues, mental status concerns, or other. Of the 28 patients, 19 had post-transplant psychiatric diagnoses. Although adjustment disorders were the most prevalent (8/19), more significant pathology was found in remaining patients including opioid abuse (4/19), PTSD (3/19), and pain disorders (3/19). Conclusion: Present analysis suggests that many pre-transplant patients have significant psychopathology. Post-transplant a number of psychosocial issues persist and can emerge on an inpatient and outpatient basis. Development of behavioral health protocols for the most common consultations will be a valuable clinical service. These interventions may improve psychosocial outcomes, decrease patient noncompliance and reduce disease burden and cost. Future prospective studies, extending period of follow up, and assessing a wider range of predictors and outcomes are needed. (Figure Preseted)