Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. METHODS: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. RESULTS: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. CONCLUSIONS: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

Early outcomes of kidney transplant recipients from donors with severe SARS-CoV-2 pneumonia: A report of 5 cases.

BACKGROUND: Transplanting kidneys from donors with a recent history of severe SARS-CoV-2 pneumonia is uncommon due to concerns about the risk of viral transmission and the quality of kidneys from these donors. To date, there are no conclusive data on viral transmission from extrapulmonary solid organ transplants. Given the prevalence of SARS-CoV-2 infections in potential donors, shortage of kidneys available for transplantation, and low risk of viral transmission, we developed a clinical protocol for accepting kidneys from donors with recent severe SARS-CoV-2 pneumonia who demonstrate preserved kidney function. MATERIALS AND METHODS: We collected data on early outcomes of 5 kidney transplant recipients from 4 deceased donors hospitalized for severe SARS-CoV-2 infection. RESULTS: Donor creatinine ranged from 0.51 to 0.60 mg/dL and kidney donor profile index (KDPI) from 14 to 52%. Three of the five kidneys were from donation after circulatory death. All recipients were fully vaccinated, and 4/5 received post-exposure prophylactic monoclonal antibody treatment. While 3 recipients had delayed graft function, all had excellent graft function at 3 or 4 weeks post-operatively. None of the recipients displayed signs or symptoms of SARS-CoV-2 infection post-transplant. CONCLUSION: Our findings suggest that kidney grafts from donors with a recent history of severe SARS-CoV-2 infection but with preserved kidney function can be safely used and have good early outcomes.

New ERAS in liver transplantation - Past, present, and next steps.

There are parallels between the history of Enhanced Recovery after Surgery (ERAS) and liver transplantation. Both have been established and advanced by innovative individuals, often going against perceived wisdom and convention. Liver transplantation has traditionally been considered too complex for ERAS pathways, despite a small number of trials showing them to be both safe and of benefit. To date, there are very few randomized controlled trials and cohort studies publishing outcomes on liver transplant patients enrolled in comprehensive ERAS pathways. To progress our field, the 2022 International Liver Transplantation Society's Consensus Conference has created expert panels to analyze the evidence in 32 domains of the liver transplantation pathway using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to generate expert recommendations. These recommendations will be voted on by the international community to gain consensus using the Danish model, and create the ERAS4OLT.org Enhanced Recovery after Liver Transplantation Pathway.

Technological Advancements in Uterus Transplantation.

Uterus transplantation is barely a decade old and in a young, evolving field it is hard to identify "technological advances" since it is, in of itself, a technological advance. Nonetheless, one can still identify advances in diagnostic imaging that have improved donor screening to avoid graft losses, highlight the adoption of robotic surgery to make the living donor uterus procurement more minimally invasive, and look to a future of biotechnology like perfusion pumps and bioengineering such as synthetic uterus to increase donor supply. Additional technologies are on the horizon and promise to shape the field further.

Robotic Donor Hysterectomy Results in Technical Success and Live Births After Uterus Transplantation: Subanalysis Within the Dallas Uterus Transplant Study (DUETS) Clinical Trial.

Minimally invasive procurement of uterine grafts for transplantation can decrease living donor recovery time. We examined recipient outcomes for grafts procured by robotic-assisted donor hysterectomies with transvaginal extraction in the Dallas UtErus Transplant Study (DUETS). All 5 grafts were successfully transplanted. Recipients had a median 4.5-hour surgical time, 0.25 L estimated blood loss, and 4-day hospital stay. Four recipients had grade III surgical complications and three had acute cellular rejection. At 18 months, graft viability was 100%, with an 80% live birth rate. This report demonstrates the feasibility and reproducible success of using uterus grafts from living donors who underwent robotic-assisted donor hysterectomy.

Longitudinal profiling of plasma and urine metabolites during liver regeneration in living liver donors.

BACKGROUND: Knowledge of metabolic processes affected by major hepatectomy (MHx), and the metabolic pathways involved in liver regeneration and recovery of function, is limited and mainly derived from animal models. Assessment of restoration of hepatic function is essential in human living liver donors (LD). METHODS: We used a targeted metabolomic approach to longitudinally quantify changes in plasma and urine biomarkers from healthy LD. The biomarkers were analyzed before MHx and at scheduled intervals up to 12 months thereafter. RESULTS: Marked changes were found in the concentration of 15 primary and secondary plasma bile acids. Most significant changes occurred 2 days after MHx and persisted for up to 3 months. In addition, there were significant changes in acylcarnitine, phospholipid, and amino acid metabolism. The sum of aromatic amino acids and the Fischer ratio, both metabolic markers of liver damage, and the symmetrically demethylated arginine to arginine ratio, a marker of kidney function, were affected. CONCLUSIONS: This is the first comprehensive longitudinal study investigating metabolic processes during recovery of liver function after MHx in LD. It provides further evidence of full restoration of metabolic processes 3 months after MHx and supports future investigation to understand how metabolic changes affect donors' hepatic function.

The Impact of Transitions, a Mental Health Literacy Intervention With Embedded Life Skills for Postsecondary Students: Preliminary Findings From a Naturalistic Cohort Study.

OBJECTIVE: Mental illness is a common medical condition to onset during adolescence. Young people who leave for postsecondary life are at an especially challenging period of lifetime when many will leave home and familiar environments for prolonged periods of time. These new circumstances may put young people at risk of developing mental health problems or disorders or exacerbate existing mental disorders. Alternatively, some young people may misinterpret the normal negative emotional states occurring as a result of these new challenges as a mental disorder requiring professional intervention. We conducted a quasiexperimental cohort study to investigate the effectiveness of a mental health literacy intervention Transitions with blended life skills to address these challenges for first-year postsecondary students. METHODS: Students (n = 2,397) from five Canadian postsecondary institutions were assigned to the intervention or the control group and were administered a survey at baseline, postintervention, and at 2-month follow-up (September 2017 to February 2018). We applied generalized linear mixed effects (PROC Mixed procedure) to test the between-group difference in the post-pre/follow-up-pre and to determine the predicted least-square mean values. RESULTS: The findings showed that students who were exposed to the Transitions intervention significantly improved their mental health knowledge, decreased stigma against mental illness, improved help-seeking attitudes and behaviours, and decreased perceived stress when compared to students who had not been exposed to the intervention. However, we did not identify significant changes in general health. This may be due to the relatively short follow-up time (2 months) to determine participants' general health status. CONCLUSIONS: Transitions delivered to first-year postsecondary students may be a beneficial intervention to help young people adjust to their new postsecondary life and improve their mental health.

Center Variation in Intention-to-Treat Survival Among Patients Listed for Liver Transplant.

In the United States, centers performing liver transplant (LT) are primarily evaluated by patient survival within 1 year after LT, but tight clustering of outcomes allows only a narrow window for evaluation of center variation for quality improvement. Alternate measures more relevant to patients and the transplant community are needed. We examined adults listed for LT in the United States, using data submitted to the Scientific Registry of Transplant Recipients. Intention-to-treat (ITT) survival was defined as survival within 1 year from listing, regardless of transplant. Mixed effects/frailty models were used to assess center variation in ITT survival. Between January 2010 and December 2016, there were 66,428 new listings at 113 centers. Overall, median 1-year ITT survival was 79.8% (interquartile range [IQR], 76.1%-83.4%), whereas 1-year waiting-list (WL) survival was 75.8% (IQR, 71.2%-79.4%), and 1-year post-LT survival was 90.0% (IQR, 87.9%-91.8%). Higher rates of ITT mortality were correlated with increased WL mortality (correlation, r = 0.76), increased post-LT mortality (r = 0.31), lower volume centers (r = -0.34), and lower transplant rate ratio (r = -0.25). Similar patterns were observed in the subgroup of WL candidates listed with Model for End-Stage Liver Disease (MELD) ≥25: median 1-year ITT survival was 65.2% (IQR, 60.2%-72.6%), whereas 1-year post-LT survival was 87.5% (IQR, 84.0%-90.9%), and 1-year WL survival was 36.6% (IQR, 27.9%-47.0%). In mixed effects modeling, the transplant center was an independent predictor of ITT survival even after adjustment for age, sex, MELD, and sociodemographic variables. Center variation for ITT survival was larger compared with post-LT survival. The measurement of ITT outcome offers a complementary method to assess center performance. This is a first step toward understanding differences in program quality beyond patient and graft survival after LT.

The Evolution of Transplantation From Saving Lives to Fertility Treatment: DUETS (Dallas UtErus Transplant Study).

OBJECTIVE: We report the results of the first 20 uterus transplants performed in our institution. SUMMARY BACKGROUND DATA: Uterus transplantation (UTx) aims at giving women affected by absolute uterine-factor infertility the possibility of carrying their own pregnancy. UTx has evolved from experimental to an established surgical procedure. METHODS: The Dallas Uterus Transplant Study (DUETS) program started in 2016. The uterus was transplanted in orthotopic position with vascular anastomoses to the external iliac vessels and removed when 1 or 2 live births were achieved. Immunosuppression lasted only for the duration of the uterus graft. RESULTS: Twenty women, median age 29.7 years, enrolled in the study, with 10 in phase 1 and 10 in phase 2. All but 2 recipients had a congenital absence of the uterus. Eighteen recipients received uteri from living donors and 2 from deceased donors. In phase 1, 50% of recipients had a technically successful uterus transplant, compared to 90% in phase 2. Four recipients with a technical success in phase 1 have delivered 1 or 2 babies, and the fifth recipient with a technical success is >30 weeks pregnant. In phase 2, 2 recipients have delivered healthy babies and 5 are pregnant. CONCLUSIONS: UTx is a unique type of transplant; whose only true success is a healthy child birth. Based on results presented here, involving refinement of the surgical technique and donor selection process, UTx is now an established solution for absolute uterine-factor infertility.

DUETS (Dallas UtErus Transplant Study): Complete report of 6-month and initial 2-year outcomes following open donor hysterectomy.

INTRODUCTION: Uterus transplantation has shown success in treating women with uterine factor infertility who want to carry their own pregnancy. METHODS: We report the medical, sexual, and psychological outcomes of our first cohort of 13 living donor hysterectomies. As we have transitioned from open to robotically assisted hysterectomy, this report represents the complete series of open donor hysterectomies at our center, all with ≥6-month postoperative outcomes. RESULTS: The open donor hysterectomy had a median of a 6.5-hour surgical time, 0.8 L estimated blood loss, 6-day hospital stay, and 28-day sick leave. Three donors had a grade III or IV complications, one reported new-onset psychological symptoms, and 9 experienced transient sexual discomfort. All complications were addressed and resolved, and all donors returned to their presurgical social and physical activities. CONCLUSION: Since uterus transplantation is not life-saving or life-extending, the risks in living uterus donation must be weighed against the benefit of giving another woman the opportunity to give birth to her own child. This report provides data to support more detailed informed consent regarding the medical, psychological, and sexual complications of open living donor hysterectomy and allows for further evaluation of the ethical acceptability of this procedure.

Impact of Prior Bariatric Surgery on Perioperative Liver Transplant Outcomes.

Bariatric surgery (BS) is effective in treating morbid obesity, but the impact of prior BS on candidacy for liver transplantation (LT) is unclear. We examined 78 patients with cirrhosis with prior BS compared with a concurrent cohort of 156 patients matched by age, Model for End-Stage Liver Disease score, and underlying liver disease. We compared rates of transplant denial after evaluation, delisting on the waiting list, and survival after LT. The median time from BS to LT evaluation was 7 years. Roux-en-Y gastric bypass was the most common BS procedure performed (63% of cohort). Nonalcoholic fatty liver disease was the leading etiology for liver cirrhosis (47%). Delisting/death on the waiting list was higher among patients with BS (33.3% versus 10.1%; P = 0.002), and the transplantation rate was lower (48.9% versus 65.2%; P = 0.03). Intention-to-treat (ITT) survival from listing to 1 year after LT was lower in the BS cohort versus concurrent cohort (1-year survival, 84% versus 90%; P = 0.05). On adjusted analysis, a history of BS was associated with an increased risk of death on the waiting list (hazard ratio [HR], 5.7; 95% confidence interval [CI], 2.2-15.1), but this impact was attenuated (HR, 4.9; 95% CI, 1.8-13.4) by the presence of malnutrition. When limited to matched controls by sex, mortality attributed to BS was no longer significant for females (P = 0.37) but was significant for males (P = 0.046). Sarcopenia, as captured by skeletal muscle index, was calculated in a subset of patients (n = 49). The total skeletal surface area was lower in the BS group (127 [105-141] cm2 versus 153 [131-191] cm2 ; P = 0.005). Rates of sarcopenia were higher among patients delisted after listing (71.4% versus 16.7%; P = 0.04). In conclusion, a history of BS was associated with higher rates of delisting on the waiting list as well as lower survival from the time of listing on ITT analysis. Presence of malnutrition and sarcopenia among patients with BS may contribute to worse outcomes.

Eversion Bile Duct Anastomosis: A Safe Alternative for Bile Duct Size Discrepancy in Deceased Donor Liver Transplantation.

Bile duct size discrepancy in liver transplantation may increase the risk of biliary complications (BCs). The aim of this study was to evaluate the safety and outcomes of the eversion bile duct anastomosis technique in deceased donor liver transplantation (DDLT) with duct-to-duct anastomosis. A total of 210 patients who received a DDLT with duct-to-duct anastomosis from 2012 to 2017 were divided into 2 groups: those who had eversion bile duct anastomosis (n = 70) and those who had standard bile duct anastomosis (n = 140). BC rates were compared between the 2 groups. There was no difference in the cumulative incidence of biliary strictures (P = 0.20) and leaks (P = 0.17) between the 2 groups. The BC rate in the eversion group was 14.3% and 11.4% in the standard anastomosis group. All the BCs in the eversion group were managed with endoscopic stenting. A severe size mismatch (≥3:1 ratio) was associated with a significantly higher incidence of biliary strictures (44.4%) compared with a 2:1 ratio (8.2%; P = 0.002). In conclusion, the use of the eversion technique is a safe alternative for bile duct discrepancy in DDLT. However, severe bile duct size mismatch may be a risk factor for biliary strictures with such a technique.

Recipient characteristics and morbidity and mortality after liver transplantation.

BACKGROUND AND AIMS: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. We sought to identify an easily applicable set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within five years after liver transplantation. METHODS: We collected national (n = 31,829, 2002-2015) and center-specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95% CI 1.48-1.72); recipient age >60 years (three patients; HR 1.29; 95% CI 1.23-1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16-1.37); diabetes (two patients; HR 1.20; 95% CI 1.14-1.27); or serum creatinine ≥1.5 mg/dl without hemodialysis (two patients; HR 1.15; 95% CI 1.09-1.22). RESULTS: Graft survival within five years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with >8 points, graft survival was 42% (model for end-stage liver disease [MELD] score <25) and 50% (MELD score 25-35) in recipients receiving grafts from donors with a donor risk index >1.7. In center-specific data within the first year, subjects with ≥5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p <0.01), higher admissions for rehabilitation (12.3% vs. 2.7%, p <0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p <0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p = 0.03) within five years. CONCLUSION: The impact of co-morbidities in an MELD-based organ allocation system need to be reassessed. The proposed clinical tool may be helpful for center-specific assessment of risk of graft failure in non-HCV patients and for discussion regarding relevant morbidity in selected subsets. LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60 years, ventilator status, diabetes, hemodialysis and creatinine >1.5 mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival.

Living uterus donation and transplantation: experience of interest and screening in a single center in the United States.

BACKGROUND: Little is known about attitudes toward uterus donation and transplantation in society and the interest of the women the treatment is aimed to assist. OBJECTIVE: This study examined the interest of recipients and living donors in our uterus transplantation program; it describes the screening protocol we developed and the results of the screening and reports demographic data and characteristics of screened candidates. STUDY DESIGN: Initial screening and evaluation included physical examinations by a gynecologist and a transplant surgeon; psychological evaluation; imaging (x-ray, computed tomography, ultrasound); blood tests; immunological testing; viral, bacterial, and fungal testing; drug screen; hormonal testing; Papanicolau smear; urinalysis; and electrocardiogram. For selected recipients, the process also included in vitro fertilization. RESULTS: A total of 351 women contacted our department with interest in participating in uterus transplantation; 272 were potential recipients and 79 were potential donors. Among these women, 179 potential recipients and 62 potential donors continued the evaluation after the initial telephone screening. The mean age of the donor candidates was 40 years; all had completed their own family, and 80% were nondirected. Most recipient candidates (92%) had an anatomical lack of the uterus, and of these, 36% had a congenital malformation. The women with a congenital uterine absence were in general younger than the women in the group whose uterus had been removed (mean of 28 and 33 years, respectively). In every step of the initial screening and evaluation process, there were donor and recipient candidates that chose not to continue the process. The reasons for self-withdrawal after expressing interest were not returning phone calls or e-mails (17 donors and 76 recipients); after initial phone screening, no longer interested (1 donor and 9 recipients); in step 1, health history questionnaire not returned after 1 reminder (10 donors and 9 recipients); step 2, not right in their current life situation (2 donors and 2 recipients), and in step 3, chose another way to achieve motherhood (1 recipient). Most donor and recipient candidates (52% and 78%, respectively) could be screened out (because of self-withdrawal or transplant team's decision) during the noninvasive and cost-efficient initial screening. CONCLUSION: Our initial experience shows a great interest in participating in a trial of uterus transplantation by both potential recipients and donors. It is the first study to show interest in nondirected donation. A sufficient but thoughtful screening process of living donors and recipients is essential and should aim both to assure donor/recipient safety and to provide good quality grafts.

Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation.

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre-transplant locoregional therapy (LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty-five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha-fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five-yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre-transplant LRT did not affect post-transplant outcomes in patients meeting Milan criteria but did result in lower three-yr HCC recurrence (7% vs. 75%, p < 0.001) and better three-yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre-transplant LRT are important factors that determine the post-transplant outcomes in patients with HCC who meet R4T3 criteria.