Risk Of Early Allograft Dysfunction Research Articles

The adverse impact of perioperative body composition abnormalities on outcomes after split liver transplantation: a multi-center retrospective cohort study.

Split liver transplantation increases graft availability, but its safe and effective utilization is insufficiently documented. This study aimed to investigate the association between perioperative body composition abnormalities and outcomes in adult split liver transplantation. 240 recipients who underwent split liver transplantation in three centers were enrolled in this retrospective cohort study. Body composition abnormalities including sarcopenia, myosteatosis, visceral obesity, and sarcopenic obesity were evaluated at baseline and one month after surgery using computed tomography. Their impact on outcomes including early allograft dysfunction, early complications, intensive care unit stay, graft regeneration rate and survival was analyzed. Recipients with sarcopenia or myosteatosis had a higher risk of early allograft dysfunction, higher early complication rate, and longer length of intensive care unit stay (all P<0.05), while there was no difference in graft regeneration rate. Recipient and graft survival were significantly worse for recipients with body composition abnormalities (all P<0.05). In multivariable Cox-regression analysis, sarcopenia (hazard ratio=1.765, P=0.015), myosteatosis (hazard ratio=2.066, P=0.002), and visceral obesity (hazard ratio=1.863, P=0.008) were independently associated with shorter overall survival. Piling up of the three factors increased the mortality risk stepwise (P<0.001). Recipients experienced skeletal muscle loss and muscle fat infiltration one month after surgery. Postoperative worsening sarcopenia (hazard ratio=2.359, P=0.009) and myosteatosis (hazard ratio=1.878, P=0.026) were also identified as independent risk factors for mortality. Sarcopenia, myosteatosis and their progression negatively affect outcomes including early allograft dysfunction, early complications, intensive care unit stay and survival after SLT. Systemic evaluation and dynamic monitoring of body composition are valuable.

How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27–24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain?

Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.

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 >50min). 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 ≤30min 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 6h. In conclusion, shorter rWIT in DBD-LT provided significantly better post-transplant outcomes.

Normothermic Machine Perfusion (NMP) of the Liver - Current Status and Future Perspectives.

A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and improvement of marginal allografts. The most exciting development in the past decade has been continuous mechanical perfusion of livers with blood or preservation solution to mitigate ischemia-reperfusion injury in contrast to the current standard of static cold storage. Two variations of machine perfusion have emerged in clinical practice. During hypothermic oxygenated perfusion the liver is perfused using a red blood cell-free perfusate at 2–10°C. In contrast, normothermic machine perfusion mimics physiologic liver perfusion using a red blood cell-based solution at 35.5–037.5°C, offering a multitude of potential advantages. Putative effects of normothermic perfusion include abrogation of hyperfibrinolysis after reperfusion and inflammation, glycogen repletion, and regeneration of adenosine triphosphate. Research in normothermic machine perfusion focuses on development of biomarkers predicting allograft quality and susceptibility to ischemia-reperfusion injury. Moreover, normothermic perfusion of marginal allografts allows for application of a variety of therapeutic interventions potentially enhancing organ quality. Both methods need to be subjected to translational investigation and evaluation in clinical trials. A clear advantage is transformation of an emergency procedure at night into a planned daytime surgery. Current clinical trials suggest that normothermic perfusion not only increases the use of hepatic allografts but is also associated with milder ischemia-reperfusion injury, resulting in a reduced risk of early allograft dysfunction and less biliary complications, including ischemic cholangiopathy, compared to static cold storage. The aim of this review is to give a concise overview of normothermic machine perfusion and its current applications, benefits, and possible advances in the future.

The Concept of Functional Graft Size: An Eternal Theme of Maximizing Donor Safety and Recipient Survival in Living Donor Liver Transplantation.

The Concept of Functional Graft Size: An Eternal Theme of Maximizing Donor Safety and Recipient Survival in Living Donor Liver Transplantation.

HPi: A Novel Parameter to Predict Graft-related Outcome in Adult Living Donor Liver Transplant.

Portal hyperperfusion is frequently associated with early allograft dysfunction (EAD). It is imperative to identify patients who would require portal inflow modulation. We aimed to identify factors associated with hyperperfusion-related graft injury and develop a predictive index for the same. Prospectively maintained database was queried to identify 135 adult living donor liver transplant recipients between September 2016 and July 2020. According to the calculated sample size, 96 patients were randomly selected for "test cohort". The remaining 39 patients made the "validation cohort." EAD was defined according to the A2ALL study. "Hyperperfusion index (HPi)," defined as posttransplant portal pressure gradient (ΔPpost)/graft-to-recipient splenic volume ratio (GRSVR), was devised on the basis of laws of flow dynamics and regression analysis. Overall, 40 patients (29.6%) had EAD, six 90-d mortalities (4.4%) were attributable to EAD. In the test cohort, EAD patients (n = 29, 30.2%) had lower GRSVR (1.00 versus 2.22, P < 0.001), higher ΔPpost (14.8 versus 11.9, P = 0.004), and HPi (20.89 versus 8.67, P < 0.001). Multivariate analysis revealed GRSVR, ΔPpost, and HPi as significant factors to predict EAD. Receiver operating characteristic determined cutoff of HPi ≥9.97 could predict EAD with sensitivity of 90% and specificity of 73% (F-score = 0.712). HPi ≥16.25 predicted 90-d mortality with sensitivity of 100% and specificity of 78.9%. Patients with higher HPi had delayed graft-related recovery. Non-EAD patients had a higher 1-y (96% versus 79%) and 2-y (88% versus 79%) survival. The cutoff of HPi was validated well in the validation cohort (F-score = 0.645) (Hosmer-Lemeshow test, P = 0.89). While predicted GRSVR may help identify at-risk patients preoperatively, intraoperatively calculated HPi is more accurate in identifying patients who would require portal inflow modulation. Achieving an HPi below target cutoff significantly decreases the risk of EAD even in low-GRSVR patients.

Early Allograft Dysfunction Increases Hospital Associated Costs After Liver Transplantation-A Propensity Score-Matched Analysis.

Concepts to ameliorate the continued mismatch between demand for liver allografts and supply include the acceptance of allografts that meet extended donor criteria (ECD). ECD grafts are generally associated with an increased rate of complications such as early allograft dysfunction (EAD). The costs of liver transplantation for the health care system with respect to specific risk factors remain unclear and are subject to change. We analyzed 317 liver transplant recipients from 2013 to 2018 for outcome after liver transplantation and hospital costs in a German transplant center. In our study period, 1‐year survival after transplantation was 80.1% (95% confidence interval: 75.8%‐84.6%) and median hospital stay was 33 days (interquartile rage: 24), with mean hospital costs of €115,924 (SD €113,347). There was a positive correlation between costs and laboratory Model for End‐Stage Liver Disease score (rs = 0.48, P < 0.001), and the development of EAD increased hospital costs by €26,229. ECD grafts were not associated with a higher risk of EAD in our cohort. When adjusting for recipient‐associated risk factors such as laboratory Model for End‐Stage Liver Disease score, recipient age, and split liver transplantation with propensity score matching, only EAD and cold ischemia increased total costs. Conclusion: Our data show that EAD leads to significantly higher hospital costs for liver transplantation, which are primarily attributed to recipient health status. Strategies to reduce the incidence of EAD are needed to control costs in liver transplantation.

A nomogram for prediction of early allograft dysfunction in living donor liver transplantation.

Liver transplantation is the treatment of choice for end-stage liver diseases. However, early allograft dysfunction (EAD) is frequently encountered and associated with graft loss or mortality after transplantation. This study aimed to establish a predictive model of EAD after living donor liver transplantation. A total of 77 liver transplants were recruited to the study. Multivariate analysis was utilized to identify significant risk factors for EAD. A nomogram was constructed according to the contributions of the risk factors. The predictive values were determined by discrimination and calibration methods. A cohort of 30 patients was recruited to validate this predictive model. Four independent risk factors, including donor age, intraoperative blood loss, preoperative alanine aminotransferase (ALT), and reperfusion total bilirubin, were identified and used to build the nomogram. The c-statistics of the primary cohort and the validation group were 0.846 and 0.767, respectively. The calibration curves for the probability of EAD presented an acceptable agreement between the prediction by the nomogram and the actual incidence. In conclusion, the study developed a new nomogram for predicting the risk of EAD following living donor liver transplantation. This model may help clinicians to determine individual risk of EAD following living donor liver transplantation.

Donor Hepatectomy and Implantation Time Are Associated With Early Complications After Liver Transplantation: A Single-center Retrospective Study.

Donor hepatectomy and liver implantation time reduce long-term graft and patient survival after liver transplantation. It is not known whether these surgical times influence early outcomes after liver transplantation. This single-center study evaluated the effect of donor hepatectomy and implantation time on the risk of nonanastomotic biliary strictures (NAS) occurring within 1 year and of early allograft dysfunction (EAD) after deceased-donor solitary liver transplantation, adjusting for other donors, recipient, and surgical factors. Of 917 transplants performed between January 2000 and December 2016, 106 (11.56%) developed NAS and 247 (27%) developed EAD. Donor hepatectomy time (median 35 min, IQR: 26-46) was an independent risk factor of NAS [adjusted hazard ratio, 1.19; 95% CI, 1.04-1.35; P = 0.01]. Implantation time (median 80 min, IQR: 69-95) was independently associated with EAD [adjusted odds ratio (OR), 1.15; 95% CI,1.07-1.23; P < 0.0001). The risk of EAD was increased by anastomosis time of both portal vein (adjusted OR, 1.26; 95% CI, 1.12-14.42; P = 0.0001) and hepatic artery (adjusted OR, 1.13; 95% CI, 1.04-1.22; P = 0.005). The magnitude of these effects was similar in donation after circulatory death liver grafts. Donor hepatectomy and implantation time negatively affect short-term outcomes.

Early allograft dysfunction paradox: Is the increasing donor age and BMI a concern?

Background: In recent years, there has been an increase in the use of graft from older donors and with higher BMI. There is a concern regarding the effect of this change in practice on the incidence of Early Allograft Dysfunction (EAD). Materials and Methods: Data regarding liver function, ischemic times, donor history and complications for all adults, elective, first liver transplant performed with whole grafts, in the last five years were extracted from a prospectively maintained database.EAD was defined according to Olthoff et al (bilirubin = 10mg/dL on day 7, INR = 1.6 on day 7, and ALT >2000 IU/L within the first 7 days). Results: 476 liver transplants met the criteria for this study; data analysis was performed for 100 transplants (77 DBDs, 23 DCDs) performed between September 2017 and 2018. Incidence of EAD was 30%, 24.7% in DBDs and 47.8% in DCDs (p=0.041).Donor BMI was significantly higher in the cases that developed EAD (28.6 vs 26.2, p=0.05) although this wasn't confirmed as significant risk factor in the univariate analysis. There was no significant difference in donor age between the 2 groups (47.1 vs 50.8, p=0.291) but a donor age above 61 years was a protective factor against the risk of EAD at the univariate analysis (p=0.032, RR=0.242).Other risk factors for EAD were, DCD graft (p=0.037, RR 2.798) and cold ischemia above 522 minutes (p=0.035, RR 3.185); while EAD increased the incidence of sepsis (p<0.001, RR=5.524), CVVH (p=0.022, RR= 3.879), graft loss (p=0.027, RR=6.8), recipient mortality (p=0.065, RR 5.231) and morbidity (p=0.08, RR 2.667). Conclusions: EAD can affect up to one third of liver transplant recipients and it can lead to sepsis, renal impairment and graft loss. More data are necessary to determine the role of donor age and BMI and other risk factors.

Predictive utility of the C-reactive protein to albumin ratio in early allograft dysfunction in living donor liver transplantation: A retrospective observational cohort study.

This study was performed to determine the association between the ratio of C-reactive protein to albumin (CRP/ALB) and the risk of early allograft dysfunction (EAD) in patients undergoing living donor liver transplantation (LDLT). A total of 588 adult patients undergoing LDLT were retrospectively investigated, after 22 were excluded because of signs of overt infection or history of ALB infusion. The study population was classified into high and low CRP/ALB ratio groups according to EAD. All laboratory variables, including CRP and ALB, had been collected on the day before surgery. A percentage value for the CRP/ALB ratio (%) was calculated as CRP/ALB × 100. After LDLT, 83 patients (14.1%) suffered EAD occurrence. A higher CRP/ALB ratio was independently associated with risk of EAD, Model for End-stage Liver Disease score, fresh frozen plasma transfusion, and donor age. Based on a cutoff CRP/ALB ratio (i.e., > 20%), the probability of EAD was significantly (2-fold) higher in the high versus low CRP/ALB group. The predictive utility of CRP/ALB ratio for EAD was greater than those of other inflammatory markers. In addition, patients with a high CRP/ALB ratio had poorer survival than those with a low CRP/ALB ratio during the follow-up period. The easily calculated CRP/ALB ratio may allow estimation of the risk of EAD after LDLT and can provide additional information that may facilitate the estimation of a patient's overall condition.

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

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. 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. 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. 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.

Recipient Outcomes with Younger Donors Undergoing Living Donor Liver Transplantation.

IntroductionThe impact of donor age on liver transplantation is well known. Data on an appropriate donor age cut-off for living donor liver transplantation (LDLT) with a background of hepatitis C (HCV) is generally limited. The objective of this study was to determine whether limiting donor age to less than 35 years improved outcomes in patients with HCV-related end-stage liver disease (ESLD).MethodsThis was a retrospective review of 169 patients who underwent LDLT for HCV-related ESLD. The patients were divided into two groups based on whether they received grafts from donors ≤ 35 (Group 1) or > 35 (Group 2) years of age. Kaplan Meier curves were used to determine survival. Uni and multivariate analysis were performed to determine independent predictors of mortality.ResultsMean donor age was 25.1 ± 5.2 and 40.1 ± 3.4 years (P < 0.0001). Early allograft dysfunction (EAD) was seen in 11.7% patients in Group 1 versus 29.6% in Group 2 (P = 0.02). A significant difference in mortality was present between the two groups, i.e., 33.3% versus 15.8% (P = 0.04). The estimated four-year overall survival (OS) was 78% and 64% (P = 0.03). Upon doing univariate analysis, the donor age (P = 0.04) and EAD (P = 0.006) were found to be significant variables for mortality. On multivariate analysis, EAD was the only independent predictor of mortality (Hazard ratio: 2.6; confidence interval: 1.1 - 5.8; P = 0.01).ConclusionOpting for younger donors (≤ 35 years) for HCV-related ESLD patients lowers the risk of EAD and improves overall survival.

Passive mesenterico-saphenous shunt: An alternative to portocaval anastomosis for tailored portal decompression during liver transplantation

Temporary portocaval shunt has a positive impact on short-term outcomes after liver transplantation. An alternative to temporary portocaval shunt is a distal passive decompression through mesenterico-saphenous shunt. The purpose of this study was to compare outcomes of these two types of surgical portosystemic shunt and discuss their respective place during the anhepatic phase. Patients transplanted with portal decompression during a 4-year period were included. Patients were compared according to two types of surgical decompression techniques: temporary portocaval shunt (n = 44) and mesenterico-saphenous shunt (n = 77). Spontaneous >5-mm portosystemic shunts were described as absent, nonpersistent, distal, or proximal. Intraoperative portal pressure variations and inhospital course were compared between the two groups, with special attention on the impact of competing spontaneous and surgical shunts. Mesenterico-saphenous shunt and temporary portocaval shunt showed a comparable hemodynamic efficiency, with no significant difference in terms of portal pressure variations. We found no significant difference in terms of reperfusion syndrome (P = .956), transfusion rate (P = .575), renal failure (P = .239) nor early allograft dysfunction (P = .976). There was a significantly higher risk of early allograft dysfunction when competing surgical and spontaneous shunts were used (P = .002) with a lesser hemodynamic efficiency (analysis of variance test; P = .04). Portacaval or mesenterico-saphenous shunts offer similar hemodynamic efficiency without impacting the outcomes after liver transplantation. Their respective place and the place of portal decompression should be discussed regarding the presence of portal thrombosis and pre-existing portosystemic shunts. Evaluation of the anatomy and the efficiency of these shunts may guide tailored portal decompression.

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

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. 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. 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. 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. 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.

Circulating sterols as predictors of early allograft dysfunction and clinical outcome in patients undergoing liver transplantation.

IntroductionSensitive and specific assessment of the hepatic graft metabolism after liver transplantation (LTX) is essential for early detection of postoperative dysfunction implying the need for consecutive therapeutic interventions.ObjectivesHere, we assessed circulating liver metabolites of the cholesterol pathway, amino acids and acylcarnitines and evaluated their predictive value on early allograft dysfunction (EAD) and clinical outcome in the context of LTX.MethodsThe metabolites were quantified in the plasma of 40 liver graft recipients one day pre- and 10 days post-LTX by liquid chromatography/tandem mass spectrometry (LC–MS/MS). Plant sterols as well as cholesterol and its precursors were determined in the free and esterified form; lanosterol in the free form only. Metabolites and esterification ratios were compared to the model for early allograft function scoring (MEAF) which is calculated at day 3 post-LTX from routine parameters defining EAD.ResultsThe hepatic esterification ratio of all sterols, but not amino acids and acylcarnitine concentrations, showed substantial metabolic disturbances post-LTX and correlated to the MEAF. In ROC analysis, the low esterification ratio of β-sitosterol and stigmasterol from day 1 and of the other sterols from day 3 were predictive for a high MEAF, i.e. EAD. Additionally, the ratio of esterified β-sitosterol and free lanosterol were predictive for all days and the esterification ratio of the other sterols at day 3 or 4 post-LTX for 3-month mortality.ConclusionLow ratios of circulating esterified sterols are associated with a high risk of EAD and impaired clinical outcome in the early postoperative phase following LTX.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1129-z) contains supplementary material, which is available to authorized users.

Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors.

Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with ≤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.

A novel objective method for deceased donor and recipient size matching in liver transplantation.

Although the consequences of implantation of a large whole liver graft into a small recipient such as compression and compromise of graft perfusion are well known, no accepted measure to aid in donor-to-recipient size matching exists. Donor liver graft and recipient native liver weights as well as donor and recipient size and amount of ascites were investigated in 1953 patients who underwent liver transplantation using deceased donor grafts between January 2002 and July 2013. We used a previously described formula for liver resections (standardized total liver volume [sTLV] = -794.41 + 1267.28 × body surface area [m(2)]) for calculating sTLV, in the current cohort of deceased liver donors. Early allograft dysfunction (EAD) and graft survival were the primary outcome measures. The formula for calculating sTLV for liver resections was validated as an accurate predictor of liver volume in the current cohort of deceased liver donors (r(2) = 0.45; P < 0.001). A cutoff point of sTLV ratio ≥ 1.25 was determined through receiver operating characteristic curves, and patients were dichotomized into 2 groups. In the sTLV ratio ≥ 1.25 group, 50% of patients developed EAD compared to 25% of patients in the sTLV ratio < 1.25 group (P < 0.001). The proportion of patients developing graft failure within 90 days was 9.6% in the sTLV ratio ≥ 1.25 group and 5.4% in the sTLV ratio < 1.25 group (P = 0.045). This study validates the use of the sTLV for prediction of actual donor liver weight in the transplant setting. Using this formula, donors with a calculated sTLV size ratio ≥ 1.25 have an increased risk of EAD and therefore caution should be used when that value is exceeded. This adjusted size ratio can be used as a decision aid when considering donor and recipient matching with potential liver organ offers.

PTH-136 Activation of the pregnane X receptor (PXR) reduces the risk of early allograft dysfunction following liver transplantation

<h3>Introduction</h3> There has been increasing interest in the pregnane X receptor (PXR) in recent years as a promising drug target for the treatment of inflammatory liver disease. Our group has previously demonstrated that activation of the PXR reduces oxidative stress and fibrosis in a rat model of liver ischaemia-reperfusion injury. The aim of this study was to investigate the effect of PXR activation on early graft function in clinical liver transplantation. <h3>Method</h3> Data was collected retrospectively for all patients receiving liver transplants in a major transplant centre in the UK over the past three years. Patients were divided into high and low PXR activation groups based on the potency and number of PXR-activating drugs administered over the first week of transplantation. Early allograft dysfunction (EAD) was measured using a validated scoring system and was compared between the two groups in addition to graft and patient survival. <h3>Results</h3> Eighty three patients were considered eligible for inclusion in this study (n = 43 and 40 in the low and high PXR activation groups respectively). The incidence of EAD was significantly higher in the low PXR activation group (30.2% vs. 10% in the high PXR activation group; P &lt; 0.05). No significant differences in graft or patient survival were demonstrated in this small cohort. <h3>Conclusion</h3> Activation of the PXR resulted in a reduction in EAD following liver transplantation in the clinical setting; consistent with our previous results in the animal model. Our findings have important implications for the potential reduction of graft loss following DCD liver transplantation. <h3>Disclosure of interest</h3> None Declared.