Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for End-stage Liver Disease Score of 40.

OBJECTIVE: To determine the association of sex with access to liver transplantation among candidates with the highest possible model for end-stage liver disease score (MELD 40). BACKGROUND: Women with end-stage liver disease are less likely than men to receive liver transplantation due in part to MELD's underestimation of renal dysfunction in women. The extent of the sex-based disparity among patients with high disease severity and equally high MELD scores is unclear. METHODS: Using national transplant registry data, we compared liver offer acceptance (offers received at match MELD 40) and waitlist outcomes (transplant vs death/delisting) by sex for 7654 waitlisted liver transplant candidates from 2009 to 2019 who reached MELD 40. Multivariable logistic and competing-risks regression was used to estimate the association of sex with the outcome and adjust for the candidate and donor factors. RESULTS: Women (N = 3019, 39.4%) spent equal time active at MELD 40 (median: 5 vs 5 days, P = 0.28) but had lower offer acceptance (9.2% vs 11.0%, P < 0.01) compared with men (N = 4635, 60.6%). Adjusting for candidate/donor factors, offers to women were less likely accepted (odds ratio = 0.87, P < 0.01). Adjusting for candidate factors, once they reached MELD 40, women were less likely to be transplanted (subdistribution hazard ratio = 0.90, P < 0.01) and more likely to die or be delisted (subdistribution hazard ratio = 1.14, P = 0.02). CONCLUSIONS: Even among candidates with high disease severity and equally high MELD scores, women have reduced access to liver transplantation and worse outcomes compared with men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.

DCD liver transplant in patients with a MELD over 35.

Introduction: Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. Methods: We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. Results: In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). Discussion: In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

The Reality of Inadequate Patient Care and the Need for a Global Action Framework in Organ Donation and Transplantation.

BACKGROUND: Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. METHODS: We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. RESULTS: We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. CONCLUSIONS: This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.

Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Optimizing pre-donation physiologic evaluation for enhanced recovery after living liver donation - Systematic review and multidisciplinary expert panel recommendations.

BACKGROUND: While preoperative physiologic evaluation of live liver donors is routinely performed to ensure donor safety and minimize complications, the optimal approach to this evaluation is unknown. OBJECTIVES: We aim to identify predonation physiologic evaluation strategies to improve postoperative short-term outcomes, enhance donor's recovery, and reduce length of stay. We also aim to provide multidisciplinary expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: The systematic review followed PRISMA guidelines, and the recommendations were formulated using GRADE approach and experts' opinion. The search included retrospective or prospective studies, describing outcomes of physiologic evaluation predonation. The outcomes of interest were length of stay, postoperative complications (POC), recovery after donation, and mortality. PROSERO protocol ID CRD42021260662. RESULTS: Of 1386 articles screened, only three retrospective cohort studies met eligibility criteria. Two studies demonstrated no impact of age (< 70 years) on POC. Increased body mass index's (BMI) association with POC was present in one study (23.8 vs 21.7 kg/m2 , OR 1.67 (1.14-2.48), P = .01) and absent in another (< 30 vs 30-35 kg/m2 , P = .61). One study demonstrated decreased risk for postdonation subclinical hepatic dysfunction in donors with higher normal platelet count (PLT). None of the studies noted donor death. Given the scarce data on predonation physiologic testing, the expert panel recommended a battery of tests to guide clinical practice and future investigations. CONCLUSION: Advancing age (60-69 years) is not a contraindication for liver donation. There is insufficient evidence for a specific predonation BMI cut-off. Abbreviated predonation physiologic testing is recommended in all candidates. Comprehensive testing is recommended in high-risk candidates while considering the pretest probability in various populations (Quality of evidence; Low to Very Low | Grade of Recommendation; Strong).

International Travel for Liver Transplantation: A Comprehensive Assessment of the Impact on the United States Transplant System.

BACKGROUND: International travel for transplantation remains a global issue as countries continue to struggle in establishing self-sufficiency. In the United States, the United Network for Organ Sharing (UNOS) requires citizenship classification at time of waitlisting to remain transparent and understand to whom our organs are allocated. This study provides an assessment of patients who travel internationally for liver transplantation and their outcomes using the current citizenship classification used by UNOS. METHODS: Adult liver UNOS data from 2003 to 2019 were used. Patients were identified as citizens, noncitizen, nonresidents (NCNR), or noncitizen residents (NC-R) according to citizenship status. Descriptive statistics compared demographics among the waitlisted patients and demographics and donor characteristics among transplant recipients. A competing risks model was used to examine waitlist outcomes. The Kaplan-Meier method and Cox proportional hazards were used for posttransplant outcomes. RESULTS: There were significant demographic differences according to citizenship group among waitlisted (n = 125 652) and transplanted (n = 71 536) patients. Compared with US citizens, NCNR was associated with a 9% increase in transplant (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 1.00-1.18; P = 0.04), and NC-R was associated with a 24% decrease in transplant (SHR, 0.76; 95% CI, 0.72-0.79; P < 0.0001) and a 23% increase in death or removal for being too sick (SHR, 1.23; 95% CI, 1.14-1.33; P < 0.0001). US citizens had significantly inferior graft and patient survival (P < 0.001). CONCLUSIONS: Though the purpose of the citizenship classification system is transparency, the results of this study highlight significant disparities in the access to and outcomes following liver transplantation according to citizenship status.

Expedited evaluation for liver transplantation: A critical look at processes and outcomes.

BACKGROUND: Most patients are listed for liver transplant (LT) following extensive workup as outpatients ("conventional evaluation"). Some patients undergo urgent evaluation as inpatients after being transferred to a transplant center ("expedited evaluation"). We hypothesized that expedited patients would have inferior survival due to disease severity at the time of transplant and shorter workup time. METHODS: Patients who underwent evaluation for LT at our institution between 2012 and 2016 were retrospectively reviewed. The expedited and conventional cohorts were defined as above. Living donor LT recipients, combined liver-kidney recipients, acute liver failure patients, and re-transplant patients were excluded. We compared patient characteristics and overall survival between patients who received a transplant following expedited evaluation and those who did not, and between LT recipients based on expedited or conventional evaluation. RESULTS: Five-hundred and nine patients were included (110 expedited, 399 conventional). There was no difference in graft or patient survival at 1 year for expedited versus conventional LT recipients. In multivariable analysis of overall survival, only Donor Risk Index (HR 1.97, CI 1.04-3.73, P = .037, per unit increase) was associated with increased risk of death. CONCLUSIONS: Patients who underwent expedited evaluation for LT had significant demographic and clinical differences from patients who underwent conventional evaluation, but comparable post-transplant survival.

"The use of bilateral continuous erector spinae plane blocks for postoperative analgesia after right-sided living donor hepatectomy: A feasibility study".

BACKGROUND: Postoperative pain after living donor hepatectomy is significant. Postoperative coagulopathy may limit the use of epidural analgesia, the gold standard for pain control in abdominal surgery. The erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we examined the effect of continuous ESPB, administered via catheters, on perioperative opioid requirements after right living donor hepatectomies for liver transplantation. METHODS: We performed a retrospective cohort study in patients undergoing right living donor hepatectomy. Twenty-four patients who received preoperative ESPB were compared to 51 historical controls who did not receive regional anesthesia. The primary endpoint was the total amount of oral morphine equivalents (OMEs) required on the day of surgery and postoperative day (POD) 1. RESULTS: Patients in the ESPB group required a lower total amount of OMEs on the day of surgery and POD 1 [141 (107-188) mg] compared the control group [293 (220-380) mg; P < .001]. CONCLUSIONS: The use of continuous ESPB significantly reduced opioid consumption following right living donor hepatectomy.

Standardizing Discharge Opioid Prescriptions in Kidney Transplant Patients Decreases Opioid Usage.

BACKGROUND: Kidney transplant recipients are frequently prescribed excess opioids at discharge relative to their inpatient requirements. Recipients who fill prescriptions after transplant have an increased risk of death and graft loss. This study examined the impact of standardized prescriptions on discharge amount and number of outpatient refills. MATERIALS AND METHODS: A historical cohort (Group 1) was compared to a cohort without patient-controlled analgesia (Group 2) and a cohort in which providers prescribed no opioids to patients who required none on the day prior to discharge, and 10 pills to those who required opioids on the day prior (Group 3). Demographics, oral morphine equivalents (OMEs) prescribed on the day prior to and at discharge, and outpatient refills were collected. RESULTS: 270 recipients were included. There was a nonsignificant trend towards lower OMEs on the day prior to discharge in Groups 2 and 3. Nonopioid adjunct use increased (P < 0.001). Discharge OMEs significantly decreased (mean 87.2 in Group 1, 62.8 in Group 2, 26.6 in Group 3, P< 0.001). The number of patients discharged without opioids increased (23.8% of Group 1, 37.5% of Group 2, 60.6% of Group 3, P < 0.001). Group 3, Asian descent, and lower OMEs on the day prior were factors significantly associated with decreased discharge OMEs on multivariable linear regression. Twelve percent of Group 2 and 2% of Group 3 patients received an outpatient refill (P = 0.02). CONCLUSIONS: A protocol targeting discharge opioids significantly reduced the amount of opioids prescribed in kidney transplant recipients; most patients subsequently received no opioids at discharge.

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines.

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons' knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.

Opioid use prior to liver transplant is associated with increased risk of death after transplant.

BACKGROUND: Opioids are generally discouraged and used sparingly in liver transplant (LT) candidates prior to LT. This study examined the relationship between opioid use at the time of LT and graft and patient survival following transplantation. METHODS: A retrospective single center cohort study of LT recipients from June 2012 to December 2019 was performed. Primary outcomes were graft and patient survival, analyzed with the Kaplan-Meier method and Cox proportional hazards models; primary predictor was active opioid prescription at LT. RESULTS: 751 LT recipients were included; 16% had an opioid prescription at LT. Post-transplant death was significantly greater in opioid users (pvalue<0.001). In a multivariable Cox model examining predictors of death, opioid use remained associated with a significant increase in the risk of death (HR 2.4 CI 1.5-4.0, p < 0.001) even after controlling for other factors. CONCLUSION: Opioid use at LT is associated with a markedly increased risk of death following transplant.

Exploration of Individual and System-Level Well-being Initiatives at an Academic Surgical Residency Program: A Mixed-Methods Study.

Importance: Physician well-being is a critical component of sustainable health care. There are few data on the effects of multilevel well-being programs nor a clear understanding of where and how to target resources. Objective: To inform the design of future well-being interventions by exploring individual and workplace factors associated with surgical trainees' well-being, differences by gender identity, and end-user perceptions of these initiatives. Design, Setting, and Participants: This mixed-methods study among surgical trainees within a single US academic surgical department included a questionnaire in January 2019 (98 participants, including general surgery residents and clinical fellows) and a focus group (9 participants, all clinical residents who recently completed their third postgraduate year [PGY 3]) in July 2019. Participants self-reported gender (man, woman, nonbinary). Exposures: Individual and organizational-level initiatives, including mindfulness-based affective regulation training (via Enhanced Stress Resilience Training), advanced scheduling of time off, wellness half-days, and the creation of a resident-driven well-being committee. Main Outcomes and Measures: Well-being was explored using validated measures of psychosocial risk (emotional exhaustion, depersonalization, perceived stress, depressive symptoms, alcohol use, languishing, anxiety, high psychological demand) and resilience (mindfulness, social support, flourishing) factors. End-user perceptions were assessed through open-ended responses and a formal focus group. Results: Of 98 participants surveyed, 64 responded (response rate, 65%), of whom 35 (55%) were women. Women vs men trainees were significantly more likely to report high depersonalization (odds ratio [OR], 5.50; 95% CI, 1.38-21.85) and less likely to report high mindfulness tendencies (OR, 0.17; 95% CI, 0.05-0.53). Open-ended responses highlighted time and priorities as the greatest barriers to using well-being resources. Focus group findings reflected Job Demand-Resource theory tenets, revealing the value of individual-level interventions to provide coping skills, the benefit of advance scheduling of time off for maintaining personal support resources, the importance of work quality rather than quantity, and the demoralizing effect of inefficient or nonresponsive systems. Conclusions and Relevance: In this study, surgical trainees indicated that multilevel well-being programs would benefit them, but tailoring these initiatives to individual needs and specific workplace elements is critical to maximizing intervention effects.

Retransplantation After Living Donor Liver Transplantation: Data from the Adult to Adult Living Donor Liver Transplantation Study.

BACKGROUND: The use of living donor liver transplantation (LDLT) for primary liver transplantation (LT) may quell concerns about allocating deceased donor organs if the need for retransplantation (re-LT) arises because the primary LT did not draw from the limited organ pool. However, outcomes of re-LT after LDLT are poorly studied. The purpose of this study was to analyze the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) data to report outcomes of re-LT after LDLT, with a focus on long-term survival after re-LT. METHODS: A retrospective review of A2ALL data collected between 1998 and 2014 was performed. Patients were excluded if they received a deceased donor LT. Demographic data, postoperative outcomes and complications, graft and patient survival, and predictors of re-LT and patient survival were assessed. RESULTS: Of the 1065 patients who underwent LDLT during the study time period, 110 recipients (10.3%) required re-LT. In multivariable analyses, hepatitis C virus, longer length of stay at LDLT, hepatic artery thrombosis, biliary stricture, infection, and disease recurrence were associated with an increased risk of re-LT. Patient survival among re-LT patients was significantly inferior to those who underwent primary transplant only at 1 (86% versus 92%), 5 (64% versus 82%), and 10 years (44% versus 68%). CONCLUSIONS: Approximately 10% of A2ALL patients who underwent primary LDLT required re-LT. Compared with patients who underwent primary LT, survival among re-LT recipients was worse at 1, 5, and 10 years after LT, and re-LT was associated with a significantly increased risk of death in multivariable modeling (hazard ratios, 2.29; P < 0.001).

Live Donor Liver Transplantation in the United States: Impact of Share 35 on Live Donor Utilization.

BACKGROUND: Share 35 was a policy implemented in 2013 to increase regional sharing of deceased donor livers to patients with model for end-stage liver disease ≥ 35 to decrease waitlist mortality for the sickest patients awaiting liver transplantation (LT). The purpose of this study was to determine whether live donor liver transplantation (LDLT) volume was impacted by the shift in allocation of deceased donor livers to patients with higher model for end-stage liver disease scores. METHODS: Using Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files, we identified all adults who received a primary LT between October 1, 2008, and March 31, 2018. LT from October 1, 2008, through June 30, 2013, was designated as the pre-Share 35 era and July 1, 2013, through March 31, 2018, as the post-Share 35 era. Primary outcomes included transplant volumes, graft survival, and patient survival in both eras. RESULTS: In total, 48 779 primary adult single-organ LT occurred during the study period (22 255 pre-Share 35, 26 524 post). LDLT increased significantly (6.8% post versus 5.7% pre, P < 0.001). LDLT volume varied significantly by region (P < 0.001) with regions 2, 4, 5, and 8 demonstrating significant increases in LDLT volume post-Share 35. The number of centers performing LDLT increased only in regions 4, 6, and 11. Throughout the 2 eras, there was no difference in graft or patient survival for LDLT recipients. CONCLUSIONS: Overall, LDLT volume increased following the implementation of Share 35, which was largely due to increased LDLT volume at centers with experience in LDLT, and corresponded to significant geographic variation in LDLT utilization.