Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Current status and recent advances of liver transplantation from donation after cardiac death

The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.

Primary graft dysfunction after liver transplantation

BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay and have higher mortality and graft loss rates compared with those without graft dysfunction. However, because of the lack of universally accepted definition, early diagnosis of graft dysfunction is difficult. Additionally, numerous factors affect the allograft function after transplantation, making the prediction of PGD more difficult. The present review was to analyze the literature available on PGD and to propose a definition.DATA SOURCE: A search of PubMed (up to the end of 2012) for English-language articles relevant to PGD was performed to clarify the characteristics, risk factors, and possible treatments or interventions for PGD.RESULTS: There is no pathological diagnostic standard; many documented definitions of PGD are different. Many factors such as donor status, procurement and transplant process and recipient illness may affect the function of graft, and ischemia reperfusion injury is considered the direct cause. Potentia managements which are helpful to improve graft function were investigated. Some of them are promising.CONCLUSIONS: Our analyses suggested that the definition of PGD should include one or more of the following variables: (1)bilirubin ≥10 mg/dL on postoperative day 7; (2) internationa normalized ratio ≥1.6 on postoperative day 7; and (3) alanine aminotransferase or aspartate aminotransferase 】2000 IU/L within 7 postoperative days. Reducing risk factors may decrease the incidence of PGD. A majority of the recipients could recover from PGD; however, when the graft progresses intoprimary non-function, the patients need to be treated with retransplantation.

Predictive factors of short term outcome after liver transplantation: A review

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Compared efficacy of preservation solutions on the outcome of liver transplantation:Meta-analysis

AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31^(st), 2017. The inclusion criteria were comparative, randomized controlled trials(RCTs) for deceased donor liver(DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin(UW) solution or histidinetryptophan-ketoglutarate(HTK), Celsior(CS) and Institut Georges Lopez(IGL-1) solutions. Fifteen RCTs(1830 livers) were included; the primary outcomes were primary non-function(PNF) and one-year posttransplant graft survival(OGS-1). RESULTS All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1(RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1(RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSION Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

Liver retransplantation: indications and outcomes

BACKGROUND: Liver transplantation is a life-saving the- rapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% pa- tients may lose the grafts caused by a variety of reasons. This review covers the most frequent indications for liver retransplantation as well as the results and specific problems with each indication. DATA RESOURCES: Searching MEDLINE (1997-2003) for articles on liver retransplantation. RESULTS: The most frequent indications of liver retrans- plantation are primary non-function, hepatic artery throm- bosis, graft rejection and recurrent diseases. The results af- ter liver retransplantation remain inferior to those after first transplantation. CONCLUSION: Liver retransplantation, which is the only means of prolonging survival in those patients whose initial graft has failed, makes an important contribution to overall survival.

Meta-analysis of the efficacy and safety of extended right liver transplantation versus whole liver transplantation

Objective:To compare the differences in postoperative survival and complications between extended right liver transplantation(ERLT)and whole liver transplantation(WLT).Methods:The Chinese and English databases were searched for clinical studies on comparing ERLT with WLT for end-stage liver disease from the date of database construction to April 15,2022.The searched literature was de-duplicated and selected according to the order of title,abstract and content,after which NOS quality evaluation was performed for literature that matched the study.Postoperative complications and survival data were extracted from the eligible literature and subjected to Meta-analysis with Review Manager 5.3,and finally data sensitivity analysis and publication bias tests were performed.Results:The complication of ERLT such as biliary complications[OR=1.77,95%CI=(1.39,2.25),P<0.00001],biliary leakage[OR=2.16,95%CI=(1.64,2.84),P<0.0001],total vascular complications[OR=2.00,95%CI=(1.48,2.70),P<0.0001],hepatic arterial thrombosis[OR=2.06,95%CI=(1.50,2.83),P<0.00001],re-Transplantation[OR=1.93,95%CI=(1.53,2.45),P<0.00001]have a higher occurrence rate compared with WLT.While the biliary stenosis[OR=0.74,95%CI=(0.48,1.15),P=0.18],hepatic portal vein thrombosis[OR=1.72,95%CI=(0.84,3.49),P=0.14],primary non-function[OR=1.27,95%CI=(0.80,2.02),P=0.32]had no statistically difference in the incidence of complications after liver transplantation.In terms of survival,ERLT had lower 1-year graft survival rate[OR=0.64,95%CI=(0.54,0.76),P<0.00001]and patient survival rate[OR=0.75,95%CI=(0.62,0.91),P=0.003]than WLT.Fortunately,there was no statistically difference in 5-year graft survival rate[OR=0.97,95%CI=(0.76,1.23),P=0.78]and 5-year patient survival rate[OR=0.94,95%CI=(0.78,1.14),P=0.54].Conclusion:ERLT is a safe and effective treatment for adult end-stage liver disease.As a surgical method with postoperative complications and survival similar to that of WLT,ERLT can increase the source of donor liver.

Predictors of graft function and survival in second kidney transplantation: A single center experience

BACKGROUND The increasing kidney retransplantation rate has created a parallel field of research,including the risk factors and outcomes of this advanced form of renal replacement therapy.The presentation of experiences from different kidney transplantation centers may help enrich the literature on kidney retransplantation,as a specific topic in the field of kidney transplantation.AIM To identify the risk factors affecting primary graft function and graft survival rates after second kidney transplantation(SKT).METHODS The records of SKT cases performed between January 1977 and December 2014 at a European tertiary-level kidney transplantation center were retrospectively reviewed and analyzed.Beside the descriptive characteristics,the survivals of patients and both the first and second grafts were described using Kaplan-Meier curves.In addition,Kaplan-Meier analyses were also used to estimate the survival probabilities at 1,3,5,and 10 post-operative years,as well as at the longest followup duration available.Moreover,bivariate associations between various predictors and the categorical outcomes were assessed,using the suitable biostatistical tests,according to the predictor type.RESULTS Out of 1861 cases of kidney transplantation,only 48 cases with SKT were eligible for studying,including 33 men and 15 women with a mean age of 42.1±13 years.The primary non-function(PNF)graft occurred in five patients(10.4%).In bivariate analyses,a high body mass index(P=0.009)and first graft loss due to acute rejection(P=0.025)were the only significant predictors of PNF graft.The second graft survival was reduced by delayed graft function in the first(P=0.008)and second(P<0.001)grafts.However,the effect of acute rejection within the first year after the first transplant did not reach the threshold of significance(P=0.053).The mean follow-up period was 59.8±48.6 mo.Censored graft/patient survival rates at 1,3,5 and 10 years were 90.5%/97.9%,79.9%/95.6%,73.7%/91.9%,and 51.6%/83.0%,respectively.CONCLUSION Non-immediate recovery modes of the first and second graft functions were significantly associated with unfavorable second graft survival rates.Patient and graft survival rates of SKT were similar to those of the first kidney transplantation.