Risk Factors For Early Allograft Dysfunction Research Articles

Re-thinking of T-tube use in whole liver transplantation: an analysis on the risk of delayed graft function

The liver–gut axis has been identified as crucial mediator of liver regeneration. Thus, the use of a T-tube in liver transplantation (LT), which interrupts the enterohepatic bile circulation, may potentially have a detrimental effect on the early allograft functional recovery. We retrospectively analyzed a cohort of 261 patients transplanted with a whole liver graft, with a duct-to-duct biliary anastomosis, who did not develop any surgical complication within postoperative day 14. Early allograft dysfunction (EAD) was defined according to the criteria of Olthoff et al. (EAD-O), and graded according to the Model for Early Allograft Function (MEAF) score. EAD-O developed in 24.7% of recipients and the median MEAF score was 4.0 [interquartile range 2.9–5.5]. Both MEAF and EAD predicted 90-day post-LT mortality. A T-tube was used in 49.4% of cases (n = 129). After a propensity score matching for donor age, cold and warm ischemia time, donor risk index, balance of risk score, Child–Pugh class C, and MELD score, the T-tube group showed a significantly higher prevalence of EAD-O and value of MEAF than the no-T-tube group (EAD-O: 29 [34.1%] vs 16 [19.0%], p = 0.027; MEAF 4.5 [3.5–5.7] vs 3.7 [2.9–5.0], p = 0.014). In conclusion, T-tube use in LT may be a risk factor for EAD and higher MEAF, irrespective of graft quality and severity of pre-LT liver disease.

Risk factors of early liver dysfunction after liver transplantation using grafts from donation after citizen death donors

BackgroundAs an early complication after liver transplantation, early allograft dysfunction (EAD) indicates a poor prognosis. This study analyzes the risk factors related to early allograft dysfunction (EAD) after liver transplantation using grafts from donation after citizen death (DCD) to provide a reference for the prevention of EAD after DCD liver transplantation. MethodsA total of 32 patients who underwent DCD liver transplantation in the organ transplantation center of our hospital from September 2013 to January 2021 were enrolled in this study. The patients were divided into the EAD group and non-EAD group according to whether they developed EAD after transplantation. The general data of the donors and recipients before transplantation, intraoperative conditions, and clinical data within one week after transplantation were compared between the two groups, and related complications were statistically analyzed. The follow-up time was one week postoperatively or, if they died within the first week postoperatively, until the patient died. ResultsThe subjects included 10 females and 22 males, and the incidence of postoperative EAD was 25% (8/32). Four patients (12%) had primary malignant tumors (primary liver cancer and cholangiocarcinoma), and five donors (15%) had fatty liver. The univariate analysis revealed that the donor BMI (P = 0.005), degree of fatty liver (P = 0.025), aspartate aminotransferase (P = 0.001), alanine aminotransferase (P < 0.001), and total bilirubin (P = 0.009) were related to the occurrence of EAD after DCD liver transplantation. By analyzing the correlation between the incidence EAD and postoperative complications after liver transplantation using grafts from DCD donors, it was shown that the incidence of primary nonfunction (PNF) is related to EAD (P = 0.024). ConclusionDonor BMI, the degree of fatty liver, and preoperative liver function are risk factors for EAD after DCD liver transplantation, and the occurrence of EAD after DCD liver transplantation significantly increases the probability of PNF.

Detection of early allograft dysfunction at 30 min of reperfusion in liver transplantation: An intraoperative diagnostic tool with real time assessment of graft function

IntroductionDuring the anhepatic phase of liver transplantation (LT), fibrinolytic activity increases, since the liver clears tissue plasminogen activator (tPA). We hypothesize that patients who fail to reduce fibrinolytic activity following graft reperfusion will have an increased rate of early allograft dysfunction (EAD). MethodsAssessment of fibrinolysis in liver transplant recipients was quantified with thrombelastography (TEG) LY30. Changes in LY30 were assessed after graft reperfusion. The 30-min post-reperfusion LY30 was subtracted from the anhepatic LY30 quantifying fibrinolytic changes (delta-LY30). ResultsSeventy-three primary LT patients were included in the analysis. Receiver operating characteristic curve (ROC) analysis identified an inflection point of delta-LY30–5.3% as a risk factor for EAD. EAD occurred in 44% of these patients compared to 5% in high delta-LY30 (p = 0.002). ConclusionLT recipients that develop hyperfibrinolysis who fail to reduce fibrinolytic activity 30 min after graft reperfusion had an EAD rate 8-fold higher than patients who had a large reduction in LY30 following reperfusion.

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.

Prevalence of Antiphospholipid Antibody Positivity and Association of Pretransplant Lupus Anticoagulant Positivity With Early Allograft Dysfunction in Liver Transplantation

BackgroundAntiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). MethodsData of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. ResultsThe prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-β2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P < .001). Model for End-stage Liver Disease score, operation time, and C-reactive protein level remained significant after multivariable analysis. ConclusionA positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin >or=10mg/dL on day 7, international normalized ratio >or=1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk = 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk = 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function.