Short-term postoperative bacteriobilia or fungibilia in liver transplantation patients with donation after circulatory death allografts associated with a longer hospital stay: A single-center retrospective observational study in China.

BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.

Early allograft dysfunction in a pediatric liver allograft with an occult pathogenic mutation in the urea cycle.

Liver transplantation risks transferring a genetic defect in metabolic pathways, including the urea cycle. We present a case of pediatric liver transplantation complicated by metabolic crisis and early allograft dysfunction (EAD) in a previously healthy unrelated deceased donor. Allograft function improved with supportive care, and retransplantation was avoided. Because hyperammonemia suggested an enzymatic defect in the allograft, genetic testing from donor-derived deoxyribonucleic acid revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme argininosuccinate lyase. Homozygous ASL mutations precipitate metabolic crises during fasting or postoperative states, whereas heterozygous carriers retain sufficient enzyme activity and are asymptomatic. In the described case, postoperative ischemia/reperfusion injury created a metabolic demand that exceeded the enzymatic capacity of the allograft. To our knowledge, this is the first report of an acquired argininosuccinate lyase deficiency by liver transplantation and underscores the importance of considering occult metabolic variants in the allograft during EAD.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Real-world implementation of normothermic machine perfusion: A detailed analysis of intraoperative and early postoperative impact.

BACKGROUND: Outcome data for the great majority of liver normothermic machine perfusion (NMP) cases derive from the strict confines of clinical trials. Detailed specifics regarding the intraoperative and early postoperative impact of NMP on reperfusion injury and its sequelae during real-world use of this emerging technology remain largely unavailable. METHODS: We analyzed transplants performed in a 3-month pilot period during which surgeons invoked commercial NMP at their discretion. Living donor, multi-organ, and hypothermic machine perfusion transplants were excluded. RESULTS: Intraoperatively, NMP (n = 24) compared to static cold storage (n = 25) recipients required less peri-reperfusion bolus epinephrine (0 vs. 60 µg; p < .001) and post-reperfusion fresh frozen plasma (2.5 vs. 7.0 units; p = .0069), platelets (.0 vs. 2.0 units; p = .042), and hemostatic agents (0% vs. 24%; p = .010). Time from incision to venous reperfusion did not differ (3.6 vs. 3.1; p = .095) but time from venous reperfusion to surgery end was shorter for NMP recipients (2.3 vs. 2.8 h; p = .0045). Postoperatively, NMP recipients required fewer red blood cell (1.0 vs. 4.0 units; p = .0083) and fresh frozen plasma (4.0 vs. 7.0 units; p = .046) transfusions, had shorter intensive care unit stays (33.5 vs. 58.4 h; p = .012), and experienced less early allograft dysfunction according to both the Model for Early Allograft Function Score (3.4 vs. 5.0; p = .0047) and peak AST within 10 days of transplant (619 vs. 1,181 U/L; p = .036). Liver acceptance for the corresponding recipient was conditional on NMP use for 63% (15/24) of cases. CONCLUSION: Real-world NMP use was associated with significantly lower intensity of reperfusion injury and intraoperative and postoperative care that may translate into patient benefit.

Lactate concentration at the end of liver transplant: Early predictor of graft function or just one piece of the puzzle?

BACKGROUND: The post-operative course after Liver Transplantation (LT) can be complicated by early allograft dysfunction (EAD), primary nonfunction (PNF) and death. A lactate concentration at the end of transplant of ≥5 mmol/L was recently proposed as a predictive marker of PNF, EAD, and mortality; this study aimed to validate these previous reports in a large single center cohort. METHODS: This retrospective cohort study included adult liver transplant recipients who received grafts from deceased donors at our center between June 2012 and May 2021. Receiver operating characteristic (ROC) curves for the lactate concentration at the end of transplantation were computed to determine the AUC for PNF, EAD and mortality at 90 days. RESULTS: In our cohort of 1137 cases, the AUCs for lactate to predict EAD, PNF and mortality were respectively .56 (95% confidence interval [CI]: .53-.60), .69 (95% CI: .52-.85), and .74 (95% CI: .63-.84). CONCLUSION: The clinical value of lactate concentration at the end of transplantation to predict PNF, EAD and mortality at 90 days was, at best, modest, as shown by the relatively low AUCs. Our findings cannot validate previous reports that the lactate level alone is a good predictor of poor outcomes after liver transplantation.

High Systemic Immune-Inflammation Index, Predicting Early Allograft Dysfunction, Indicates High 90-Day Mortality for Acute-On-Chronic Liver Failure after Liver Transplantation.

INTRODUCTION: The aim of the study was to investigate the relationship between systemic immune-inflammation index (SII) and early allograft dysfunction (EAD) and 90-day mortality after liver transplantation (LT) in acute-on-chronic liver failure (ACLF). METHODS: Retrospective record analysis was done on 114 patients who had LT for ACLF. To identify the ideal SII, the receiver operating characteristic curve was used. The incidence of EAD and 90-day mortality following LT were calculated. The prognostic value of SII was assessed using the Kaplan-Meier technique and the Cox proportional hazards model. RESULTS: The cut-off for SII was 201.5 (AUC = 0.728, p < 0.001). EAD occurred in 40 (35.1%) patients of the high SII group and 5 (4.4%) patients of the normal SII group, p < 0.001. 18 (15.8%) deaths occurred in the high SII group and 2 (1.8%) deaths occurred in the normal SII group, p = 0.008. The multivariate analysis demonstrated that SII ≥201.5, MELD ≥27 were independent prognostic factors for 90-day mortality after LT. CONCLUSION: SII predicts the occurrence of EAD and is an independent risk factor for 90-day mortality after LT.

The impact of center volume on the utilization and outcomes of machine perfusion technology in liver transplantation: An international survey.

INTRODUCTION: Machine perfusion (MP) was developed to expand the donor pool and improve liver transplantation (LT) outcomes. Despite optimal results in clinical trials, the real-world MP benefit in centers with low-/mid-volume activity (LVCs) is still being determined. METHODS: Online survey on MP for LT, distributed to worldwide LT-centers representatives. Variables of interest included logistics, technicalities, and outcomes. Responders were grouped into high-volume centers (HVCs) (>60 LTs/year) and LVCs and results compared. RESULTS: Sixty-seven centers were included, 36 HVCs and 31 LVCs. Significant differences in MP regarded: (I) existence of an established program (80.6% vs. 41.9%; p = 0.02), (II) presence of a dedicated perfusionist (58.3% vs. 22.6%; p = 0.006), (III) duration (>4 h: 47.2% vs. 16.1%; p = 0.01), (IV) routine use (20%-40% vs. 5%-20%; p = 0.002), (V) graft utilization (>50%: 75% vs. 51.6%; p = 0.009), (VI) 90-day patient-survival (90%-100% vs. 50%-90%; p = 0.001) and (VII) subjectively perceived benefit (always vs. only in selected ECD; p = 0.009). Concordance was found for indications, type, viability tests, graft-salvage, 90-day graft-loss, and major-complications. CONCLUSIONS: This study captured a picture of MP in real-world LT-practice. Significant disparities have surfaced between LVCs and HVCs regarding logistics, utilization, and results. To close this gap, efforts should be made to more efficiently deliver dedicated support, training and mentoring to LVC teams adopting MP technology.

Biomarkers and predictive models of early allograft dysfunction in liver transplantation - A systematic review of the literature, meta-analysis, and expert panel recommendations.

BACKGROUND: Prompt identification of early allograft dysfunction (EAD) is critical to reduce morbidity and mortality in liver transplant (LT) recipients. OBJECTIVES: Evaluate the evidence supporting biomarkers that can provide diagnostic and predictive value for EAD. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach was derived from an international expert panel. Studies that investigated biomarkers or models for predicting EAD in adult LT recipients were included for in-depth evaluation and meta-analysis. Olthoff's criteria were used as the standard reference for the diagnostic accuracy evaluation. PROSPERO ID: CRD42021293838 RESULTS: Ten studies were included for the systematic review. Lactate, lactate clearance, uric acid, Factor V, HMGB-1, CRP to ALB ratio, phosphocholine, total cholesterol, and metabolomic predictive model were identified as potential early EAD predictive biomarkers. The sensitivity ranged between .39 and .92, while the specificity ranged from .63 to .90. Elevated lactate level was most indicative of EAD after adult LT (pooled diagnostic odds ratio of 7.15 (95%CI: 2.38-21.46)). The quality of evidence (QOE) for lactate as indicator was moderate according to the GRADE approach, whereas the QOE for other biomarkers was very low to low likely as consequence of study design characteristics such as single study, small sample size, and large ranges of sensitivity or specificity. CONCLUSIONS: Lactate is an early indicator to predict EAD after LT (Quality of Evidence: Moderate | Grade of Recommendation: Strong). Further multicenter studies and the use of machine perfusion setting should be implemented for validation.

Procalcitonin in early allograft dysfunction after orthotopic liver transplantation: a retrospective single centre study.

BACKGROUND: Ischemia-reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT. METHODS: Patients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed. RESULTS: Of 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7-53.8) mcg/l vs. 11.1 (5.3-25.0) mcg/l; p < 0.001 and 27.7 (9.7-51.9) mcg/l vs. 11.5 (5.5-25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD. CONCLUSION: Generally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome.

Ischemia-reperfusion injury and its relationship with early allograft dysfunction in liver transplant patients.

Ischemia-reperfusion injury (IRI) is believed to contribute to graft dysfunction after liver transplantation (LT). However, studies on IRI and the impact of early allograft dysfunction (EAD) in IRI grafts are limited. Histological IRI was graded in 506 grafts from patients who had undergone LT and classified based on IRI severity (no, minimal, mild, moderate, and severe). Of the 506 grafts, 87.4% had IRI (no: 12.6%, minimal: 38.1%, mild: 35.4%, moderate: 13.0%, and severe: 0.8%). IRI severity correlated with the incidence of EAD and graft survival at 6 months. Longer cold/warm ischemia time, recipient/donor hypertension, and having a male donor were identified as independent risk factors for moderate to severe IRI. Among 70 grafts with moderate to severe IRI, 42.9% of grafts developed EAD, and grafts with EAD had significantly inferior survival compared to grafts without EAD. Longer cold ischemia time and large droplet macrovesicular steatosis (≥20%) were identified as independent risk factors for EAD. Our study demonstrated that increased IRI severity was correlated with inferior short-term graft outcomes. Careful consideration of IRI risk factors during donor-recipient matching may assist in optimizing graft utilization and LT outcomes. Furthermore, identification of risk factors of IRI-associated EAD may guide patient management and possible timely graft replacement.

Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. Previously we reported that the liver graft assessment following transplantation (L-GrAFT7) risk score was superior to binary EAD or the model for early allograft function (MEAF) score for estimating 3-month graft failure-free survival in a single-center derivation cohort. Herein, we sought to externally validate L-GrAFT7, and compare its prognostic performance to EAD and MEAF. METHODS: Accuracies of L-GrAFT7, EAD, and MEAF were compared in a 3-center US validation cohort (n = 3,201), and a Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion (NMP) trial cohort (n = 222); characteristics were compared to assess generalizability. RESULTS: Compared to the derivation cohort, patients in the validation and NMP trial cohort had lower recipient median MELD scores; were less likely to require pretransplant hospitalization, renal replacement therapy or mechanical ventilation; and had superior 1-year overall (90% and 95% vs. 84%) and graft failure-free (88% and 93% vs. 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; p <0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT7 maintained an excellent validation AUROC of 0.78, significantly superior to binary EAD (AUROC 0.68, p = 0.001) and MEAF scores (AUROC 0.72, p <0.001). In post hoc analysis of the COPE NMP trial, the highest tertile of L-GrAFT7 was significantly associated with time to liver allograft (hazard ratio [HR] 2.17, p = 0.016), Clavien ≥IIIB (HR 2.60, p = 0.034) and ≥IVa (HR 4.99, p = 0.011) complications; post-LT length of hospitalization (p = 0.002); and renal replacement therapy (odds ratio 3.62, p = 0.016). CONCLUSIONS: We have validated the L-GrAFT7 risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to existing scores. L-GrAFT7 may standardize grading of early hepatic allograft function and serve as a clinical endpoint in translational studies (www.lgraft.com). LAY SUMMARY: Early allograft dysfunction negatively affects outcomes following liver transplantation. In independent multicenter US and European cohorts totaling 3,423 patients undergoing liver transplantation, the liver graft assessment following transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure-free survival and post-liver transplantation complications.

Short recipient warm ischemia time improves outcomes in deceased donor liver transplantation.

While adverse effects of prolonged recipient warm ischemia time (rWIT) in liver transplantation (LT) have been well investigated, few studies have focused on possible positive prognostic effects of short rWIT. We aim to investigate if shortening rWIT can further improve outcomes in donation after brain death liver transplant (DBD-LT). Primary DBD-LT between 2000 and 2019 were retrospectively reviewed. Patients were divided according to rWIT (≤30, 31-40, 41-50, and >50 min). The requirement of intraoperative transfusion, early allograft dysfunction (EAD), and graft survival were compared between the rWIT groups. A total of 1,256 patients of DBD-LTs were eligible. rWIT was ≤30min in 203 patients (15.7%), 31-40min in 465 patients (37.3%), 41-50min in 353 patients (28.1%), and >50min in 240 patients (19.1%). There were significant increasing trends of transfusion requirement (P < 0.001) and increased estimated blood loss (EBL, P < 0.001), and higher lactate level (P < 0.001) with prolongation of rWIT. Multivariable logistic regression demonstrated the lowest risk of EAD in the WIT ≤30min group. After risk adjustment, patients with rWIT ≤30 min showed a significantly lower risk of graft loss at 1 and 5-years, compared to other groups. The positive prognostic impact of rWIT ≤30min was more prominent when cold ischemia time exceeded 6 h. In conclusion, shorter rWIT in DBD-LT provided significantly better post-transplant outcomes.

Application of ischaemia-free liver transplantation improves prognosis of patients with steatotic donor livers - a retrospective study.

The use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia-free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3-year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.

Hepatic Vein Flow Index During Orthotopic Liver Transplantation as a Predictive Factor for Postoperative Early Allograft Dysfunction.

OBJECTIVES: The authors devised a hepatic vein flow index (HVFi), using intraoperative transesophageal echocardiography and graft weight, and investigated its predictive value for postoperative graft function in orthotopic liver transplant. DESIGN: Prospective clinical trial. SETTING,: Single-center tertiary academic hospital. PARTICIPANTS: Ninety-seven patients who had orthotopic liver transplant with the piggy-back technique between February 2018 and December 2019. MEASUREMENTS AND MAIN RESULTS: HVFi was defined with HV flow/graft weight. Patients who developed early graft dysfunction (EAD) had low HVFi in systole (HVFi sys, 1.23 v 2.19 L/min/kg, p < 0.01), low HVFi in diastole (HVFi dia, 0.87 v 1.54 L/min/kg, p < 0.01), low hepatic vein flow (HVF) in systole (HVF sys, 2.04 v 3.95 L/min, p < 0.01), and low HVF in diastole (HVF dia, 1.44 v 2.63 L/min, p < 0.01). More cardiac death, more vasopressors at the time of measurement, more acute rejection, longer time to normalize total bilirubin (TIME t-bil), longer surgery time, longer neohepatic time, and more packed red blood cell transfusion were observed in the EAD patients. All HVF parameters were negatively correlated with TIME t-bil (HVFi sys R = -0.406, p < 0.01; HFVi dia R = -0.442, p < 0.01; HVF sys R = -0.44, p < 0.01; HVF dia R = -0.467, p < 0.01). The receiver operating characteristic curve analysis determined the best cut-off levels of HVFi to predict occurrence of EAD (HVFi sys <1.608, HVFi dia <0.784 L/min/kg), acute rejection (HVFi sys <1.388, HVFi dia <1.077 L/min/kg), and prolonged high total bilirubin (HVFi sys <1.471, HVFi dia <1.087 L/min/kg). CONCLUSIONS: The authors' devised HVFi has the potential to predict the postoperative graft function.

[Bilary anastomotic strictures after right lobe living donor liver transplantation: a single-center experience]. / Biliarnye anastomoticheskie striktury posle transplantatsii pravoi doli pecheni ot zhivogo rodstvennogo donora: opyt odnogo transplantatsionnogo tsentra.

OBJECTIVE: To determine the incidence of AS after right lobe living donor liver transplantation with various biliary reconstructions and to identify the predictors of this complication. MATERIAL AND METHODS: A retrospective and prospective analysis included 245 RLLDLTs for the period 2011-2018 at the Burnazjan Federal Medical Biophysical Center. The results of transplantations in 207 patients aged 19-68 years (median 43 years) were assessed. There were 82 men and 125 women. Follow-up period ranged from 10 to 98 months (median 35 months). We analyzed the relationship between surgical characteristics (preoperative data of recipients and donors, graft parameters, technical features of biliary reconstruction and features of post-transplantation period) and incidence of anastomotic strictures. A total of 58 parameters were analyzed. RESULTS: AS occurred in 20 (9.7%) recipients. Median AS-free period was 5 months (range 1-44). In 17 (85%) patients, AC developed within a year after surgery. Cumulative 1-, 2- and 5-year incidence of AS was 8.3%, 8.9%, and 11%, respectively. Significant predictors of AS were impaired arterial blood supply to the graft (HR 7.8, 95% CI 2.3-26.0, p<0.001), biliary leakage ISGLS class B or C (HR 5.0, 95% CI 2.0-12.8, p<0.001), early allograft dysfunction (HR 4.2, 95% CI 1.5-11.6, p=0.006) and female recipient (HR 3.2, 95% CI 1.1-9.9, p=0.04). In our sample, variant biliary anatomy of the graft and recipient liver, as well as technical features of biliary reconstruction did not affect the risk of AS. CONCLUSION: Variant biliary anatomy of potential donor alone should not be considered as a contraindication for organ donation and right liver lobe transplantation. Precise surgical technique, high transplantation activity, as well as experience of reconstructive interventions on the bile ducts during other operations can significantly reduce the incidence of AS after RLLDLT up to 9.7%.

Model for early allograft function is predictive of early graft loss in donation after circulatory death liver transplantation.

Donation after circulatory death (DCD) liver transplantation is associated with higher rates of graft loss. In this paper, we explored whether the Model for Early Allograft Function (MEAF) predicted outcome in DCD liver transplantation. We performed a retrospective analysis of prospectively collected data from all adult DCD (Maastricht 3) livers transplanted in Cambridge and Edinburgh between 1 January 2011 and 30 June 2017, excluding those undergoing any form of machine perfusion. 187 DCD liver transplants were performed during the study period. DCD liver transplants with a lower MEAF score had a significantly better survival compared to those with a high MEAF score (Mantel-Cox P < .0001); this was largely due to early graft loss. Beyond 28 days post-transplant, there were no significant long-term graft or patient survival differences irrespective of the grade of MEAF (Mantel-Cox P = .64 and P = .43, respectively). The MEAF score correlated with the length of ICU (P = .0011) and hospital stay (P = .0007), but did not predict the requirement for retransplantation for ischemic cholangiopathy (P = .37) or readmission (P = .74). In this study, a high MEAF score predicted early graft loss, but not the subsequent need for re-transplantation or late graft failure as a result of intrahepatic ischemic bile duct pathology.

[Research progress on factors influencing early liver dysfunction after liver transplantation].

Liver transplantation is the most effective treatment for end-stage liver disease, and early graft dysfunction often occurs after surgery. Early liver dysfunction after liver transplantation has become one of the complications after liver transplantation, which seriously affects the graft and patient survival. Therefore, reducing its occurrence can be an important means to improve the prognosis of recipients after liver transplantation. This paper discusses the research progress on the definition, influencing factors, and prognosis and prediction model in order to provide better prevention and effective reference for improving the success rate and prognosis of early liver dysfunction in recipients after liver transplantation.

Neutrophil-to-lymphocyte ratio is a predictor of early graft dysfunction following living donor liver transplantation.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) is predictive of poor graft and patient survival following living donor liver transplantation (LDLT). Considering the impact of the inflammatory response on graft injury extent following LDLT, we investigated the association between neutrophil-to-lymphocyte ratio (NLR) and EAD, 1-year graft failure, and mortality following LDLT, and compared it to C-reactive protein (CRP), procalcitonin, platelet-to-lymphocyte ratio and the Glasgow prognostic score. METHODS: A total of 1960 consecutive adult LDLT recipients (1531/429 as development/validation cohort) were retrospectively evaluated. Cut-offs were derived using the area under the receiver operating characteristic curve (AUROC), and multivariable regression and Cox proportional hazard analyses were performed. RESULTS: The risk of EAD increased proportionally with increasing NLR, and the NLR AUROC was 0.73, similar to CRP and procalcitonin and higher than the rest. NLR ≥ 2.85 (best cut-off) showed a significantly higher EAD occurrence (20.5% vs 5.8%, P < 0.001), higher 1-year graft failure (8.2% vs 4.9%, log-rank P = 0.009) and higher 1-year mortality (7% vs 4.5%, log-rank P = 0.039). NLR ≥ 2.85 was an independent predictor of EAD (odds ratio, 1.89 [1.26-2.84], P = 0.002) after multivariable adjustment, whereas CRP and procalcitonin were not. Increasing NLR was independently associated with higher 1-year graft failure and mortality (both P < 0.001). Consistent results in the validation cohort strengthened the prognostic value of NLR. CONCLUSIONS: Preoperative NLR ≥ 2.85 predicted higher risk of EAD, 1-year graft failure and 1-year mortality following LDLT, and NLR was superior to other parameters, suggesting that preoperative NLR may be a practical index for predicting graft function following LDLT.

Peri-transplant lactate levels and delayed lactate clearance as predictive factors for poor outcomes after liver transplantation: A propensity score-matched study.

This study aimed to investigate risk factors for early allograft dysfunction (EAD) and outcomes after liver transplantation (LT), focusing on peri-transplant lactate clearance. We reviewed patients who underwent deceased donor LTs between 2011 and 2014. Lactate levels were checked at reperfusion and at the time of intensive care unit admission. Early lactate clearance was defined as reduction rate of lactate between the times of reperfusion and immediately after LT. Patients were categorized into the normal and delayed clearance groups. We used propensity score matching (PSM) between these two groups to estimate an impact of lactate clearance on incidence of EAD and graft survival. A total of 256 recipients were eligible for this study. Cut-off value of lactate clearance to predict occurrence of EAD was determined at 0.2 mmol/L/h. After PSM, 120 patients in the normal clearance and 36 patients in the delayed clearance group were matched. Delayed lactate clearance was considered as an independent risk factor for EAD (Odds ratio 3.49, P = 0.002). The adjusted hazard of one-year graft loss was significantly increased in the delayed clearance group (hazard ratio 6.69, P = 0.001). In conclusion, peri-transplant delayed lactate clearance may be a strong predictor for EAD and poor liver graft outcomes.

Impact of real-time metabolomics in liver transplantation: Graft evaluation and donor-recipient matching.

BACKGROUND & AIMS: There is an emerging need to assess the metabolic state of liver allografts especially in the novel setting of machine perfusion preservation and donor in cardiac death (DCD) grafts. High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS-NMR) could be a useful tool in this setting as it can extemporaneously provide untargeted metabolic profiling. The purpose of this study was to evaluate the potential value of HR-MAS-NMR metabolomic analysis of back-table biopsies for the prediction of early allograft dysfunction (EAD) and donor-recipient matching. METHOD: The metabolic profiles of back-table biopsies obtained by HR-MAS-NMR, were compared according to the presence of EAD using partial least squares discriminant analysis. Network analysis was used to identify metabolites which changed significantly. The profiles were compared to native livers to identify metabolites for donor-recipient matching. RESULTS: The metabolic profiles were significantly different in grafts that caused EAD compared to those that did not. The constructed model can be used to predict the graft outcome with excellent accuracy. The metabolites showing the most significant differences were lactate level >8.3 mmol/g and phosphocholine content >0.646 mmol/g, which were significantly associated with graft dysfunction with an excellent accuracy (AUROClactates = 0.906; AUROCphosphocholine = 0.816). Native livers from patients with sarcopenia had low lactate and glycerophosphocholine content. In patients with sarcopenia, the risk of EAD was significantly higher when transplanting a graft with a high-risk graft metabolic score. CONCLUSION: This study underlines the cost of metabolic adaptation, identifying lactate and choline-derived metabolites as predictors of poor graft function in both native livers and liver grafts. HR-MAS-NMR seems a valid technique to evaluate graft quality and the consequences of cold ischemia on the graft. It could be used to assess the efficiency of graft resuscitation on machine perfusion in future studies. LAY SUMMARY: Real-time metabolomic profiles of human grafts during back-table can accurately predict graft dysfunction. High lactate and phosphocholine content are highly predictive of graft dysfunction whereas low lactate and phosphocholine content characterize patients with sarcopenia. In these patients, the cost of metabolic adaptation may explain the poor outcomes.