Characterization of Perioperative Serotonin in Patients Undergoing Orthotopic Liver Transplantation.

Background: Platelets were shown to be relevant for liver regeneration. In particular, platelet-stored serotonin (5-HT) proved to be a pro-regenerative factor in this process. The present study aimed to investigate the perioperative course of 5-HT and evaluate associations with patient and graft outcomes after othotopic liver transplantation (OLT). Methods: 5-HT was quantified in plasma and serum of 44 OLT recipients perioperatively, and in their respective donors. Olthoff's criteria for early allograft dysfunction (EAD) were used to evaluate postoperative outcomes. Results: Patients with higher donor intra-platelet 5-HT per platelet (IP 5-HT PP) values had significantly lower postoperative transaminases (ASAT POD1: p = 0.006, ASAT POD5: p = 0.006, ASAT POD10: p = 0.02, ALAT POD1: p = 0.034, ALAT POD5: p = 0.017, ALAT POD10: p = 0.04). No significant differences were seen between postoperative 5-HT values and the occurrence of EAD. A tendency was measured that donor IP 5-HT PP is lower in donor-recipient pairs that developed EAD (p = 0.07). Conclusions: Donor IP 5-HT PP might be linked to the postoperative development of EAD after OLT, as higher donor levels are correlated with a more favorable postoperative course of transaminases. Further studies with larger cohorts are needed to validate these findings.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplantant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Rescue Allocation Modes in Eurotransplant Kidney Transplantation: Recipient Oriented Extended Allocation Versus Competitive Rescue Allocation-A Retrospective Multicenter Outcome Analysis.

BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

Challenges With the Implementation of Machine Perfusion in Clinical Liver Transplantation.

Dynamic organ preservation is a relatively old technique which has regained significant interest in the last decade. Machine perfusion (MP) techniques are applied in various fields of solid organ transplantation today. The first clinical series of ex situ MP in liver transplantation was presented in 2010. Since then, the number of research and clinical applications has substantially increased. Despite the notable beneficial effect on organ quality and recipient outcome, MP is still not routinely used in liver transplantation. Based on the enormous need to better preserve organs and the subsequent demand to continuously innovate and develop perfusion equipment further, this technology is also beneficial to test and deliver future therapeutic strategies to livers before implantation. This article summarizes the various challenges observed during the current shift from static to dynamic liver preservation in the clinical setting. The different organ perfusion strategies are discussed first, together with ongoing clinical trials and future study design. The current status of research and the impact of costs and regulations is highlighted next. Factors contributing to costs and other required resources for a worldwide successful implementation and reimbursement are presented third. The impact of research on cost-utility and effectivity to guide the tailored decision-making regarding the optimal perfusion strategy is discussed next. Finally, this article provides potential solutions to the challenging field of innovation in healthcare considering the various social and economic factors and the role of clinical, regulatory, and financial stakeholders worldwide.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). METHODS: A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. RESULTS: It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. CONCLUSIONS: Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation.

Introduction: Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients. Methods: We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients. Results: Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE. Discussion: These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

MELD-Na Alterations on the Liver Transplant Waiting List and Their Impact on Listing Outcome.

BACKGROUND: Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. METHOD: 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. RESULTS: Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. CONCLUSIONS: Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.

A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.53-0.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation.

A Multi-Centre Non-Interventional Study to Assess the Tolerability and Effectiveness of Extended-Release Tacrolimus (LCPT) in De Novo Liver Transplant Patients.

BACKGROUND: Available tacrolimus formulations exhibit substantial inter- and intra-individual variability in absorption and metabolism. The present non-interventional cohort study aimed to assess the tolerability and effectiveness of the once-daily tacrolimus formulation, LCPT, in hepatic allograft recipients in real life. MATERIALS AND METHODS: This study was conducted in Austria and the Czech Republic between July 2016 and August 2019. Patients aged ≥ 18 years old received LCPT per the approved label and local clinical routine. All the participants provided informed consent. Patients newly treated with tacrolimus (de novo) directly after transplantation were observed for six months. The relevant clinical variables were tacrolimus trough level (TL), total daily dose (TDD), number of dose adjustments, kidney and liver function, and tolerability. RESULTS: Of the 70 analyzed patients, 72.9% were male and 85.7% were aged < 65 years old. The mean (SD) time to achieve tacrolimus target TL was 6.4 (4.6) days after 4.4 (4.0) dose adjustments; thereafter, TL remained stable throughout observation at approximately 8 ng/mL. The LCPT TDD at initiation was 8 mg and decreased by a median of 41.4% to 5 mg at 6 months. Liver function continuously improved, and kidney function remained stable. LCPT was well tolerated with 24 adverse events in eight patients (17 related to immunosuppression, mostly mild renal insufficiency, and hematological adverse events); two serious unrelated adverse events were reported (atrial flutter and liver dysfunction). CONCLUSIONS: TL was rapidly attained with few dose adaptations after LCPT initiation in de novo liver transplant patients. Liver function rapidly improved, whereas kidney function remained normal. LCPT was well-tolerated in this population.

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.

BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.

Optimum timing of antithymocyte globulin in relation to adoptive regulatory T cell therapy.

Reducing the recipient's T cell repertoire is considered to increase the efficacy of regulatory T cell (Treg) therapy. This necessitates timing the administration of antithymocyte globulin (ATG) early enough before adoptive cell therapy (ACT) so that residual serum ATG does not deplete the transferred Tregs. The optimum time point in this regard has not been defined. Herein, we report the effects of residual serum ATG on the viability of an in vitro expanded Treg cell product used in a clinical trial of ACT in kidney transplant recipients (NCT03867617). Patients received ATG monotherapy (either 6 or 3 mg/kg body weight) without concomitant immunosuppression 2 to 3 weeks before transplantation and Treg transfer. An anti-ATG immunoglobulin G (IgG) immune response was elicited in all patients within 14 days. In turn, the elimination of total and Treg-specific ATG was accelerated substantially over control patients receiving the same dose of ATG with concomitant immunosuppression. However, ATG serum concentrations of <1 µg/mL, which had previously been reported as subtherapeutic threshold, triggered apoptosis of Tregs in vitro. Therefore, ATG levels need to decline to lower levels than those previously thought for efficacious Treg transfer. In 5 of 6 patients, such low levels of serum ATG considered safe for Treg transfer were reached within 2 weeks after ATG administration.

The impact of COVID-19 on liver transplantation programs in Austria.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) has affected liver disease management. The impact of the COVID-19 pandemic on the Austrian orthotopic liver transplantation (OLT) programs, however, has not been systematically investigated. METHODS: All patients listed for OLT in Austria during 2020-2021 were studied. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, vaccinations, infections, mortality and the overall number of OLTs (vs. pre-COVID-19: 2015-2019) were analyzed. RESULTS: Overall, 490 patients (median age: 58.0 years, 70.4% men, hepatocellular carcinoma: 27.3%) were listed for OLT in Austria in 2020-2021. Alcohol-related cirrhosis (35.3%), cholestatic (16.7%) and viral liver disease (13.9%) were the main etiologies. Of the patients 61.2% underwent OLT and 8.8% died while on the waiting list. The number of OLTs performed during COVID-19 (2020: n = 150; 2021: n = 150) remained unchanged compared to pre-COVID-19 (median: n = 152). Among waiting list patients, 7.7% (n = 31/401) were diagnosed with COVID-19 and 7 (22.6%) of these patients died. By the end of 2021, 45.1% (n = 176/390; 82.8% mRNA vaccinations) and 28.8% (105/365) of patients received 2 and 3 SARS-CoV­2 vaccinations, respectively. After two SARS-CoV­2 vaccinations, antibodies more often remained undetectable in patients vaccinated post-OLT (25.6% vs. 6.5% in patients vaccinated pre-OLT; p = 0.034). Patients with three vaccinations after OLT had lower antibody titers than patients vaccinated pre-OLT (post-OLT: 513.5, IQR 44.4-2500.0 vs. pre-OLT: 2500.0, IQR 1462.0-2500.0 BAU/mL; p = 0.020). CONCLUSION: The number of OLTs in Austria remained unchanged during COVID-19. SARS-CoV­2 infections were rare but associated with high mortality in patients on the Austrian OLT waiting lists. SARS-CoV­2 vaccination rates at the end of 2021 were suboptimal, while serological response was better in patients vaccinated pre-OLT vs. post-OLT.

Leptin increases hepatic triglyceride export via a vagal mechanism in humans.

Recombinant human leptin (metreleptin) reduces hepatic lipid content in patients with lipodystrophy and overweight patients with non-alcoholic fatty liver disease and relative hypoleptinemia independent of its anorexic action. In rodents, leptin signaling in the brain increases very-low-density lipoprotein triglyceride (VLDL-TG) secretion and reduces hepatic lipid content via the vagus nerve. In this randomized, placebo-controlled crossover trial (EudraCT Nr. 2017-003014-22), we tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. A single metreleptin injection stimulated hepatic VLDL-TG secretion (primary outcome) and reduced hepatic lipid content in fasted, lean men (n = 13, age range 20-38 years) but failed to do so in metabolically healthy liver transplant recipients (n = 9, age range 26-62 years) who represent a model for hepatic denervation. In an independent cohort of lean men (n = 10, age range 23-31 years), vagal stimulation by modified sham feeding replicated the effects of metreleptin on VLDL-TG secretion. Therefore, we propose that leptin has anti-steatotic properties that are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liver axis.

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion.

Women Leadership in Liver Transplantation-Results of an International Survey.

BACKGROUND: The International Liver Transplantation Society (ILTS) has placed a strong focus on achieving gender equality and equity in liver transplant (LT). We aimed to understand gender distribution in leadership positions among LT physicians around the world and within ILTS. METHODS: In 2019, the ILTS Equality, Diversity, and Inclusion Committee distributed a survey to obtain granular data on gender and characteristics of transplant physicians as well as those in leadership positions in each center. Additionally, data were collected on the gender composition of the ILTS membership, council, chairpersons, and committees and from the United Network for Organ Sharing. RESULTS: Data were collected from 243 transplant centers. Thirty-two (13.2%) had at least 1 woman as the director of LT, chief of transplant surgery, or chief of transplant hepatology. Of the 243 centers, 133 reported the age and gender of the leadership personnel. Women physicians comprised 152 of the 833 transplant surgeons (18.2%) and 298 of the 935 hepatologists (31.9%). Among the 1331 ILTS physician members, 588 (44.2%) provided gender information in their member profiles, and 155 (26.3%) identified themselves as women. Of the 26 ILTS leadership positions, 7 (26.9%) were held by women. CONCLUSIONS: This analysis of worldwide gender distribution in the LT physician workforce showed notable gender disparity in LT leadership around the globe and within the ILTS. These data provide a launching point for promoting and achieving gender equality and equity in LT.

Sex Disparities in Outcome of Patients with Alcohol-Related Liver Cirrhosis within the Eurotransplant Network-A Competing Risk Analysis.

Alcohol use disorder (AUD) is one of the most important risk factors for the development of alcohol-related liver cirrhosis (ALC). Importantly, psychiatrists are an integral part of the interdisciplinary care for patients with AUD and ALC. The aim of the current study was to investigate whether sex influences the outcome within this group of patients. For this purpose, data of all registrations for liver transplantations due to ALC within the Eurotransplant region from 2010 to 2019 were analyzed for sex disparities using competing risk models and in-between group comparisons. Relevant sex differences in registration numbers (24.8% female) and investigated outcomes were revealed. Risk ratios for a positive outcome, i.e., transplantation (0.74), and those of adverse outcomes, i.e., removal from waiting list (1.44) and death on waiting list (1.10), indicated a relative disadvantage for female patients with ALC. Further, women listed for liver transplantations were significantly younger than their male counterparts. Notably, sex disparities found in registration and outcome parameters were independent of differences found in the prevalence of AUD and liver transplantations. Further research is necessary to identify the underlying mechanisms and establish strategies to ensure equity and utility in liver transplantations due to ALC.

Biliary Viability Assessment and Treatment Options of Biliary Injury During Normothermic Liver Perfusion-A Systematic Review.

In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies in their clinical routine. Normothermic machine perfusion (NMP) is primarily used to determine the quality of extended criteria donor (ECD) organs and for logistical reasons. The vast majority of studies, which assessed the viability of perfused grafts, focused on hepatocellular injury. However, biliary complications are still a leading cause of post-transplant morbidity and the need for re-transplantation. To evaluate the extent of biliary injury during NMP, reliable criteria that consider cholangiocellular damage are needed. In this review, different approaches to assess damage to the biliary tree and the current literature on the possible effects of NMP on the biliary system and biliary injury have been summarized. Additionally, it provides an overview of novel biomarkers and therapeutic strategies that are currently being investigated. Although expectations of NMP to adequately assess biliary injury are high, scant literature is available. There are several biomarkers that can be measured in bile that have been associated with outcomes after transplantation, mainly including pH and electrolytes. However, proper validation of those and other novel markers and investigation of the pathophysiological effect of NMP on the biliary tree is still warranted.

Proteinuria in Deceased Kidney Transplant Donors for Prediction of Chronic Lesions in Pretransplant Biopsies: A Prospective Observational Study.

BACKGROUND: Pretransplant kidney graft biopsies have been suggested for organ quality assessment. Data on the association between donor proteinuria and organ quality of deceased donors are not available. METHODS: In this prospective study, we analyzed 147 pretransplant kidney biopsies from 88 deceased adult donors procured and transplanted consecutively at the Medical University Vienna between July 2017 and May 2020. Lesions in each renal compartment were scored from 0 to 5 with each ascending score representing a 20% increase in organ damage. A chronic lesions score was calculated including glomerulosclerosis, intima fibrosis, hyalinosis, interstitial fibrosis, and tubular atrophy. RESULTS: The median chronic lesion score was 2 (interquartile range [IQR] 1-4) and the median donor urinary protein to creatinine ratio (UPCR) was 382 mg/dL (IQR 222-703). There was a positive correlation between UPCR and number of chronic lesions (ß 0.15, 95% confidence interval, 0.03-0.28; P = 0.019). Biopsies with 2 or more lesions had a median UPCR of 486 mg/dL (IQR 251-717) compared with 274 mg/dL (IQR 211-556; P = 0.016) in biopsies with <2 lesions. The risk for detection of 2 or more lesions rose by 18% for every log increase in UPCR (risk ratio 1.18, 95% confidence interval, 1.03-1.25; P = 0.017). Multivariable and sensitivity analysis revealed an independent and robust association between chronic lesions and UPCR. CONCLUSIONS: Donor UPCR is associated with chronic lesions in pretransplant deceased donor kidney graft biopsies. This finding justifies further investigation of donor proteinuria for the assessment of organ quality and outcome.

When is the optimal time to discharge patients after liver transplantation with respect to short-term outcomes? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Several factors associated with prolonged hospital stay have been described. A recent study demonstrated that hospital length of stay (LOS) is directly associated with an increased cost for liver transplantation (LT) and may be associated with greater mortality; however, the factors associated with post-LT mortality are also related to a prolonged hospital stay, that is, those factors are confounders. Thus, the actual impact of the length of post-LT hospital stay on both short-term and long-term patient and graft survival remains uncertain. OBJECTIVES: To identify the optimal time to discharge patients after LT with respect to short-term outcomes; readmission rate, 30-90-mortality and morbidity. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Initial search keywords for screening were as follows; ((discharge AND (time OR "time point" OR "time-point")) OR "length of hospital stay" OR "length of stay") AND ((liver OR hepatic) AND (transplant OR transplantation)). PROSPERO ID: CRD42021245598 RESULTS: The strength of recommendation was rated as Weak, and we did not identify the direction of recommendations regarding the optimal timing after LT concerning short-term outcomes, including "Readmission rate," six studies on 30- and/or 90-day mortality, and five studies on "30- and/or 90-day morbidity rate." CONCLUSIONS: Evidence is scarce to judge the optimal timing to discharge patients after LT with respect to short-term outcomes. In centers with robust outpatient follow-up, discharge can occur safely as early as post-transplant 6-8 days (Quality of Evidence [QOE]; Low | Grade of Recommendation; Weak).

Oblique Carinal End-to-end Anastomosis for Pig Bronchus in Organ Donor and Lung Transplant Recipient.

Pig bronchi are rare anomalies in which the right upper lobe bronchus originates above the carina. During surgery this can lead to technical challenges associated with the bronchial anastomosis, especially during lung transplantation. We herein report the case of a combined liver-lung transplantation with a pig bronchus in both the organ donor and transplant recipient. In both cases the bronchi originated slightly above the level of the carina facilitating an oblique resection and a single tracheobronchial anastomosis with a running suture. Follow-up bronchoscopy showed a completely healed anastomosis with no evidence of malacia or stenosis.