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Background: Health care-associated infection (HAI) represent a global health problem with an increase in hospital stays, deaths, and monetary costs. Recipients of solid organ transplants are a population at risk. The objectives of the study were to characterize the incidence of HAI in renal and hepatic transplant recipients as well as to compare them with the population without transplants in intensive care units (ICU)., Methods: The data on the incidence of HAI, localization, microorganisms, and demographics were taken from the patients admitted between the years 2013 to 2018 (n = 4307) from the registration of the Project for the Reduction of Nosocomial Infection in Intensive Care Units. The variables were compared with those of renal transplant (n = 96) and liver transplants (n = 68) recipients., Results: Renal transplant recipients showed 26% incidence of HAI. The most frequent were surgical site infection (SSI), urinary tract infection, and primary bacteremia; the most frequent microorganism was Staphylococcus spp, mortality 3.8%. Liver transplant recipients showed 41% incidence of HAI. The most frequent were tracheobronchitis associated with mechanical ventilation, SSI, and primary bacteremia; the most frequent microorganism was Staphylococcus spp, mortality 37%. The population without transplants in the ICU showed 17% incidence of HAI. The most frequent were respiratory infections associated with mechanical ventilation, primary bacteremia, and SSI; the most frequent microorganism was Acinetobacter spp, mortality 21%., Conclusions: HAI in recipients of solid organ transplants (renal and hepatic) have a higher incidence than in a population without transplants. The location and causal microorganisms have particularities that must be taken into account for the development of prevention protocols., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background Optimal haemostasis management in orthotropic liver transplant (OLT) could reduce blood loss and transfusion volume, improve patient outcomes and reduce cost. Methods We performed a study including 336 OLTs to evaluate the clinical and cost effectiveness of a new point-of-care (POC)-based haemostatic management approach in OLT patients. Results In terms of health benefit we found that the new approach showed a significant reduction in transfusion requirements (red blood cell transfusion units were reduced from 5.3±4.6 to 2.8±2.9 [p<0.001], free frozen plasma from 3.1±3.3 to 0.4±1.0 [p<0.001] and platelets from 2.9±3.9 to 0.4±0.9 [p<0.001], transfusion avoidance, 9.7% vs. 29.1% [p<0.001] and massive transfusion, 14.5% vs. 3.8% [p=0.001]); we also found a significant improvement in patient outcomes, such, reoperation for bleeding or acute-kidney-failure (8.3% vs. 2.4%, p=0.015; 33.6% vs. 5.4%, p<0.001), with a significant reduction in the length of the hospital total stay (40.6±13.8 days vs. 38.2±14.4 days, p=0.001). The lowest cost incurred was observed with the new approach (€73,038.80 vs. €158,912.90) with significant patient saving associated to transfusion avoidance (€1278.36), ICU-stay (€3037.26), total-stay (€3800.76) and reoperation for bleeding (€80,899.64). Conclusions POC haemostatic monitoring during OLT is cost effective.

Background: Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation., Methods: This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders., Results: Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation., Conclusion: Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.

Background: Studies suggest that vascular invasion may be a superior prognostic marker compared with traditional selection criteria, e.g. Milan criteria. This study aimed to investigate the prognostic value of micro and macrovascular invasion in a large database material., Methods: Patients liver transplanted for HCC and cirrhosis registered in the European Liver Transplant Registry (ELTR) database were included. The association between the Milan criteria, Up-to-seven criteria and vascular invasion with overall survival and HCC specific survival was investigated with univariate and multivariate Cox regression analyses., Results: Of 23,124 patients transplanted for HCC, 9324 had cirrhosis and data on explant pathology. Patients without microvascular invasion, regardless of number and size of HCC nodules, had a five-year overall survival of 73.2%, which was comparable with patients inside both Milan and Up-to-seven criteria. Patients without macrovascular invasion had an only marginally reduced survival of 70.7% after five years. Patients outside both Milan and Up-to-seven criteria without micro or macrovascular invasion still had a five-year overall survival of 65.8%., Conclusion: Vascular invasion as a prognostic indicator remains superior to criteria based on size and number of nodules. With continuously improving imaging studies, microvascular invasion may be used for selecting patients for transplantation in the future., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT) have a variable 5-year survival rate limited mostly by tumor recurrence. The etiology, age, sex, alcohol, Child-Pugh, and the immunesuppressor have been associated with tumour recurrence. The expression of ΔNp73 is related to the reduced survival of patients with HCC. The study evaluated the expression of p63 and p73 isoforms and cell death receptors, and their relation to tumour recurrence and survival. The results were in vitro validated in HCC cell lines., Methods: HCC sections from patients submitted to OLT were used. The in vitro study was done in differentiated hepatitis B virus (HBV)-expressing Hep3B and control HepG2 cells. The expression of cell death receptors and cFLIPS/L, caspase-8 and -3 activities, and cell proliferation were determined in control and p63 and p73 overexpressing HCC cells., Results: The reduced tumor expression of cell death receptors and TAp63 and TAp73, and increased ΔNp63 and ΔNp73 expression were associated with tumor recurrence and reduced survival. The in vitro study demonstrated that HBV-expressing Hep3B vs HepG2 cells showed reduced expression of p63 and p73, cell death receptors and caspase activation, and increased cFLIPL/cFLIPS ratio. The overexpression of TAp63 and TAp73 exerted a more potent pro-apoptotic and anti-proliferative effects in Hep3B than HepG2-transfected cells which was related to cFLIPL upregulation., Conclusions: The reduction of TAp63 and TAp73 isoforms, rather than alteration of ΔN isoform expression, exerted a significant functional repercussion on cell death and proliferation in HBV-expressing HepB cells.

Background: Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma., Methods: This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively., Results: Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%., Conclusions: Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.

Background: Optimal haemostasis management can improve patient outcomes and reduce blood loss and transfusion volume in orthotopic-liver-transplant (OLT)., Methods: We performed a prospective study including 200 consecutive OLTs. The first 100 patients were treated according to the clinic's standards and the next 100 patients were treated using the new point-of-care (POC)-based haemostasis management strategy. Transfusion parameters and other outcomes were compared between groups., Results: Transfusion requirements were reduced in the POC group. The median and IQR of red-blood-cells (RBC) transfusion units were reduced from 5 [2-8] to 3 [0-5] (p < 0.001), plasma from 2 [0-4] to 0 (p < 0.001), and platelets from 1 [0-4] to 0 [0-1] (p < 0.001), into the POC group only four patients received tranexamic acid and fibrinogen transfusion rate was 1.13 ± 1.44 g (p = 0.001). We also improved the incidence of transfusion avoidance, 5% vs. 24% (p < 0.001) and reduced the incidence of massive transfusion (defined as the transfusion of more than 10 RBC units), 13% vs. 2% (p = 0.005). We also observed a relationship between RBC transfusion requirements and preoperative haemoglobin, and between platelet transfusion and preoperative fibrinogen levels. The incidence of postoperative complications, such as, reoperation for bleeding, acute-kidney-failure or haemodynamic instability was significantly lower (13.0% vs. 5%, p = 0.048, 17% vs. 2%, p < 0.001, and 29% vs. 16%, p = 0.028). Overall, blood product transfusion was associated with increased risk of postoperative complications., Conclusions: A haemostatic therapy algorithm based on POC monitoring reduced transfusion and improved outcome in OLT., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Health assessment of the transplanted organ is very important due to the relationship of long-term survival of organ transplant recipients and health organ maintenance. Nowadays, the measurement of cell-free DNA from grafts in the circulation of transplant recipients has been considered a potential biomarker of organ rejection or transplant associated complications in an attempt to replace or reduce liver biopsy. However, methods developed to date are expensive and extremely time-consuming. Our approach was to measure the SRY gene, as a male organ biomarker, in a setting of sex-mismatched female recipients of male donor organs., Methods: Cell-free DNA quantization of the SRY gene was performed by real-time quantitative PCR beforehand, at the moment of transplantation during reperfusion (day 0) and during the stay at the intensive care unit. Beta-globin cell-free DNA levels, a general cellular damage marker, were also quantified., Results: Beta-globin mean values of patients, who accepted the graft without any complications during the first week after surgery, diminished from day 0 until patient stabilization. This decrease was not so evident in patients who suffered some kind of post-transplantation complications. All patients showed an increase in SRY levels at day 0, which decreased during hospitalization. Different complications that did not compromise donated organs showed increased beta-globin levels but no SRY gene levels. However, when a donated organ was damaged the patients exhibited high levels of both genes., Conclusion: Determination of a SRY gene in a female recipient's serum is a clear and specific biomarker of donated organs and may give us important information about graft health in a short period of time by a non-expensive technique. This approach may permit clinicians to maintain a close follow up of the transplanted patient.

In 2004, we defined the genetic mismatch in the glutathione S-transferase T1 (GSTT1) gene positive donor/null recipient as a risk factor to develop de novo immune hepatitis (IH) after liver transplant (LT), which is always associated with production of donor-specific anti-GSTT1 antibodies. However, there are several unresolved questions, such as why some of these patients produce antibodies, why others do not and why not all of the patients with antibodies develop the disease. The aim of this study was to evaluate the influence of several variables in the production of anti-GSTT1 antibodies and/or de novo IH. The study group included 35 liver-transplanted patients. The number of patients not producing antibodies was significantly higher in the group treated with Tac-based immunosuppression compared with the CsA-based group (94.1% vs. 5.9%, p = 0.001). Additionally, a protective effect of the Tac-based therapy vs. the CsA-based therapy was observed with regard to development of de novo IH (80.8% vs. 19.2%, p = 0.003). In conclusion, the choice of calcineurin inhibitor may influence the development of de novo IH mediated by anti-GSTT1 antibodies., (© 2010 John Wiley & Sons A/S.)

Sex inequities in liver transplantation (LT) have been documented in several, mostly USbased, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000--2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource. [ABSTRACT FROM AUTHOR]

Data comparing long‐term effectiveness and safety of once‐daily tacrolimus formulations in de novo liver transplantation are scarce. We compared the effectiveness, pharmacokinetic profile, and safety of LCPT (Envarsus) and PR‐Tac (Advagraf) for up to 12 months post‐transplant. Adult de novo liver transplant recipients who started IR‐Tac (Prograf) and were converted to LCPT or PR‐Tac 3–5 days post‐transplant were included. Data from 163 patients were analyzed, 87 treated with LCPT and 76 with PR‐Tac. The incidence of treatment failure was 30.5% in the LCPT group versus 23.0% in the PR‐Tac group (p =.291). Biopsy‐proven acute rejection (BPAR) was reported in 26.8% of patients in the LCPT group and 17.6% in the PR‐Tac group (p =.166). Graft loss was experienced in one patient (1.2%) in the LCPT group and three patients (4.1%) in the PR‐Tac group (p =.346). Death was registered in three patients (3.7%) in the LCPT group and three patients (4.1%) in the PR‐Tac group (p >.999). Patients in the LCPT group showed 45.7% higher relative bioavailability (Cmin/total daily dose [TDD]; p <.01) with similar Cmin and 33.3% lower TDD versus PR‐Tac (p <.01). The evolution of renal function, safety profile, and the incidence of post‐transplant renal failure, dyslipidemia, obesity, hypertension, and diabetes mellitus were similar in patients treated with LCPT and PR‐Tac. In de novo liver transplant patients, LCPT and PR‐Tac showed comparable effectiveness with higher relative bioavailability, similar Cmin and lower TDD in the LCPT group. Renal function, safety, and post‐transplant complications were comparable in LCPT and PR‐Tac groups. [ABSTRACT FROM AUTHOR]

(1) Background: Graft-cell-free DNA (cfDNA) in the circulation of liver transplant recipients has been proposed as a noninvasive biomarker of organ rejection. The aim of this study was to detect donor-specific cfDNA (ds-cfDNA) in the recipient's serum after either liver damage or rejection using a qPCR-based method. (2) Methods: We proposed a qPCR method based on the amplification of 10 specific insertion–deletion (InDel) polymorphisms to detect donor-specific circulating DNA diluted in the recipient cfDNA. ds-cfDNA from 67 patients was evaluated during the first month post-transplantation. (3) Results: Graft rejection in the first month post-transplantation was reported in 13 patients. Patients without liver complications showed a transitory increase in ds-cfDNA levels at transplantation. Patients with rejection showed significant differences in ds-cfDNA increase over basal levels at both the rejection time point and several days before rejection. Receiver operator characteristic (ROC) analysis showed that ds-cfDNA levels discriminated rejection, with an AUC of 0.96. Maximizing both sensitivity and specificity, a threshold cutoff of 8.6% provided an estimated positive and negative predictive value of 99% and 60%, respectively. (4) Conclusions: These results suggest that ds-cfDNA may be a useful marker of graft integrity in liver transplant patients to screen for rejection and liver damage. [ABSTRACT FROM AUTHOR]

• Donation after circulatory death liver transplant offers excellent outcomes. • Perioperative hemostasis monitoring protocols with a viscoelastic point-of-care testing assay reduce blood loss and transfusion volume. • Use of machine perfusion is likely to further expand donation after circulatory death liver transplant. The aim is to compare 2 groups of liver transplant recipients, according to type of donor, within the framework of a hemostasis monitoring program using a point-of-care testing assay in terms of reduction in transfusion of blood products. This retrospective analytical observational study included 527 liver transplant recipients from 2014 to 2021. Of these, 460 were recipients of livers from donation after brain death (DBD) and 67 were orthotopic liver transplant recipients with donation after cardiac death (DCD). Statistical analysis of differences between the 2 groups included a series of intraoperative variables of blood product consumption: erythrocyte concentrate (red blood cells), fresh frozen plasma, platelets, and fibrinogen concentrates guided by algorithm with a viscoelastic technique using the ClotPro analyzer. The transfusion management was decided according to pre-established guidelines and cutoff values. The mean follow-up period was 40.3 months. Transfused red blood cells and fibrinogen units were significantly higher in the DBD group. The percentage of retransplant was significantly higher in the DCD group, and vascular complications were significantly more frequent in the DCD group (P <.05). Cox univariate analysis showed that the DCD group had a risk ratio of death significantly higher than 1. Intraoperative monitoring of hemostasis with a point-of-care testing assay reduced blood product requirements. Type of donor had prognostic utility in our cohort. We hypothesize that other variables such as extraction technique, methods used to preserve the allograft, and later complications have a significantly greater impact than perioperative hemostasis management on retransplant rates and death. [ABSTRACT FROM AUTHOR]

Our objective was to analyze the differences in posttraumatic growth in 240 liver transplant recipients based on two factors. First, self-perceived health: better (Group 1 = G1) and worse (Group 2 = G2). Second, vitality: more (Group 3 = G3) and less (Group 4 = G4). The Posttraumatic Growth Inventory, SF-36 Health Survey (Item 2) and SF-12 Health Survey (vitality dimension) were used. Firstly, analyzing main effects recipients with better (G1) compared to worse (G2) self-perceived health, showed greater posttraumatic growth. Interaction effects were found on essential posttraumatic growth domains such as new possibilities (p = 0.040), personal strength (p = 0.027), and appreciation of life (p = 0.014). Statistically significant differences showed that among transplant recipients with worse self-perceived health (G2), those with more vitality had higher levels on abovementioned posttraumatic growth dimensions. However, in transplant recipients with better self-perceived health (G1) respective dimensions were not significantly influenced by the level of vitality. Among the recipients with less vitality (G4), those with better self-perceived health showed higher scores on abovementioned posttraumatic growth dimensions. We conclude that positive self-perceived health might compensate for a lack of vitality as well as a high level of vitality may compensate for negative self-perceived health regarding the development of crucial aspects of posttraumatic growth after liver transplantation. [ABSTRACT FROM AUTHOR]

The valid assessment of the impact of transplantation on psychological well-being is highly relevant to optimize treatment. However, to date there is no standardized instrument available in Spain. The Transplant Effects Questionnaire (TxEQ) evaluates the specific problems associated with organ transplantation, such as worry about transplant, guilt regarding the donor, disclosure of having undergone transplantation, adherence to medical treatment and responsibility toward the donor, family, friends, or medical staff. Against this backdrop the English original version of the TxEQ was translated into Spanish and validated in a sample of 240 liver transplant recipients. Participants also filled in the Posttraumatic Growth Inventory (PTGI) and the 12-Item Short Form Health Survey (SF-12v.2). Confirmatory factor analysis of the TxEQ-Spanish revealed a five-factor structure equivalent to the English original version and satisfactory internal consistency (Cronbach's alpha: worry α = 0.82, guilt α = 0.77, disclosure α = 0.91, adherence α = 0.82, responsibility α = 0.83). Results showed that better mental quality of life was associated with higher adherence and disclosure, as well as less worry and guilt. Higher posttraumatic growth was significantly associated with worry, guilt and responsibility. Interestingly, the most powerful predictor of posttraumatic growth was worry. Analysis of variance showed an interaction effect of PTG and mental quality of life on adherence, with medium PTG being associated with significantly stronger adherence in participants with better mental quality of life. In conclusion our study could successfully adapt and validate the Spanish version of the TxEQ in a large sample of liver transplant recipients. Our findings show a complex relationship between emotional reactions to transplantation, mental quality of life and posttraumatic growth, which give further insight into inner processes supporting psychological well-being and adherence after liver transplantation. [ABSTRACT FROM AUTHOR]

Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice. [ABSTRACT FROM AUTHOR]

Studies of liver transplant (LT) patients, mainly in Asians, have evaluated the influence of the CYP3A5*1 allele and P-glycoprotein gene ABCB1 on tacrolimus pharmacokinetics or biopsy-proven acute rejection (BPAR) incidence, with no conclusive results. To investigate these issues, 98 Caucasian Spanish LT patients with tacrolimus, mycophenolate mofetil and steroids and 88 cadaveric donors were genotyped for the SNPs CYP3A5 6986G>A, ABCB1 1236C>T, ABCB1 2677G>A/T and ABCB1 3435C>T;. On day 7 post-LT, patients with a native CYP3A5*1 allele had significantly lower tacrolimus trough concentrations C0 ( P = .03) and dose-adjusted concentrations C0/D ( P = .02) than CYP3A5 *3/*3 homozygotes. Three months post-LT, patients carrying a liver with CYP3A5*1 had significantly lower C0/D ( P = .03) and took significantly higher tacrolimus doses ( P = .03) than the corresponding *3/*3 homozygotes. ABCB1 SNPs showed no significant association with tacrolimus variables. The 3-month incidence of BPAR was 10.2%, with no statistically significant differences related to CYP3A5 (14.3% in expresser vs. 9.5% in non-expresser) or ABCB1 genotype of either patient or donor. We conclude that in Caucasian Spanish LT patients, a native or graft-borne CYP3A5*1 allele tends to lower tacrolimus concentrations and increase dosage needs, but has no significant impact on the incidence of BPAR. [ABSTRACT FROM AUTHOR]

• The relevance of this article lies in the fact that it is decisive to find a prognostic scoring system that allows increasing patient and graft survival after liver transplant, and the acute and chronic liver failure–sequential evaluation of organ failure score is postulate as a possible good candidate. • The use of scoring systems that assess the global condition of the patient (not only liver function) after liver transplant is of great interest. This allows identify those patients with high scores and a higher risk of postoperative complications, being able to optimize therapeutic strategies to prevent them. The use of the Model of End-Stage Liver Disease (MELD) to predict morbidity and mortality after orthotopic liver transplant (OLT) is controversial. Acute and chronic liver failure–sequential evaluation of organ failure (CLIF-SOFA) is a new score that assess the patient's global status and that have been developed exclusively for patients with end-stage liver disease. The objective is to evaluate whether the CLIF-SOFA system predicts postoperative morbidity and mortality in the short and medium term. A cohort of 123 patients who underwent OLT in a tertiary care hospital between January 2016 and December 2017 was retrospectively analyzed. The patients were divided into 2 groups: group 1 with a CLIF-SOFA score <7 and group 2 with a score CLIF-SOFA ≥7. Patients with a CLIF-SOFA ≥7 present, with statistical significance, had higher mortality at 1 and 3 years; longer duration of admission to the critical care unit; longer hospital stay; need for prolonged mechanical ventilation; surgical reintervention; higher rate of transfusion of blood products; pulmonary, neurologic, hemodynamic, surgical, infectious, kidney, metabolic, thrombotic, vascular, and graft complications; and need for kidney replacement therapy. However, no statistically significant differences were found in mortality in the first month, the need for hospital readmission, retransplant, digestive, endocrine, nutritional, hematologic, or biliary complications, and the presence of ascites. The role of CLIF-SOFA as a prognostic factor for mortality after OLT must be taken into account. Our results should be taken with caution, and more studies are necessary. [ABSTRACT FROM AUTHOR]

• The relevance of this article lies in determining the influence of the timing of extubation on morbidity and mortality after liver transplant. • It is important to identify those processes in which early extubation is beneficial and those in which it is not. • This observational study analyzes the possible complications in both groups, and it appears that early extubation in liver transplant is a safe and cost-effective process, which decreases both morbidity and mortality in patients undergoing liver transplant. Early extubation is a fundamental element integrated into enhanced recovery protocols in orthotopic liver transplantation (OLT). The aim is to evaluate whether early extubation influences short- and medium-term postoperative morbidity and mortality. A cohort of 209 patients who underwent OLT in a tertiary hospital in a period from January 2016 to December 2018 were retrospectively analyzed. Patients were divided into 2 groups: group 1: early extubation in the intensive care unit and group 2: delayed extubation. Mortality is compared between both groups in the first month and first and third year. Postoperative morbidity was also compared. Patients in group 1 (n = 165, 79.9%) presented, with statistical significance, lower mortality at 1 month, 1 year, and 3 years; shorter duration of admission to the critical care unit and of hospital stay; lower incidence of surgical reoperation and retransplant; lower rate of transfusion of blood products; fewer pulmonary, digestive, neurologic, cardiologic, hemodynamic, kidney, surgical, infectious, metabolic, thrombotic, vascular, and graft complications; less need for kidney replacement therapy; less refractory ascites; and greater infectious risk. However, no statistically significant differences were found in the need for hospital readmission; in biliary, endocrine, nutritional, hematologic, thrombotic, and hematologic complications; or in graft rejection. In group 1, 6.6% of patients required reintubation. In group 2, 97% of patients could be extubated during the first week; 7.8% required noninvasive mechanical ventilation type bilevel positive airway pressure and 8.1% high flow. Only 2.8% of patients required tracheotomy. The role of early extubation seems key to improve outcomes in OLT because it reduces the incidence of multiple complications and mortality, with low reintubation rates. It is a feasible and safe procedure. [ABSTRACT FROM AUTHOR]

• Inadvertent perioperative hypothermia is a serious, preventable, and frequent complication in major abdominal operations, particularly in liver transplant. This causes important deleterious effects and increased perioperative morbidity. • The importance of our work lies in the fact that is has shown that using a multidisciplinary protocol, standardized, multimodal, and adjusted to the characteristics of the institution, it is possible to reduce the incidence of hypothermia and, above all, its associated complications. Inadvertent perioperative hypothermia (IPH) leads to a series of deleterious effects that can be especially in complex procedures such as liver transplant. The implementation of a protocol is key to ensure the patient's normothermia. A cohort of 209 patients who underwent liver transplant in a tertiary hospital in a period between January 2016 and December 2018 was retrospectively analyzed. The patients were divided into 2 groups: group 1, patients with normothermia (core body temperature ≥ 36°C) and group 2, patients with hypothermia (core body temperature < 36°C). Mortality between both groups at 1 month, 1 year, and 3 years is compared. Postoperative morbidity is also compared. The incidence of IPH is 21.5%. Patients with normothermia present with statistical significance: a lower mortality at 1 year; a lower need for transfusion of platelets, plasma, fibrinogen consumption, or massive polytransfusion; and lower primary graft dysfunction, graft and surgical complications, rejection, hemodynamic complications, and metabolic and surgical reintervention. No significant differences were found in mortality at 1 month or 3 years in the need for prolonged mechanical ventilation; hospital readmission; length of stay in the intensive care unit or in hospital stay; rate of red blood cell transfusion; vascular, biliary, respiratory, or digestive complications; refractory ascites; or neurologic, kidney, hematological, endocrine, thrombotic, nutritional, or infectious issues. The incidence of IPH is relatively low in our patients, based on what is described in the literature, and in most cases it is mild. There is a reduction in complications fundamentally related to the consumption of blood products and the graft. [ABSTRACT FROM AUTHOR]

• There were no differences in complication or mortality rates between the group of recipients of elderly donors and the group of recipients of younger donors. • Only vascular complications were slightly more frequent in the elderly donor group, but the differences were not statistically significant. • The use of elderly liver donors (older than 75 years) is safe, with good outcomes in terms of mid- and long-term survival, reaching 81%, 75%, and 67% at 1, 2, and 5 years, respectively. An organ shortage is the reason why it is necessary to expand the pool of donors, which can be achieved by using elderly donors. The main goal of this study is to analyze the outcomes of liver transplant (LT) when it is performed with donors older than 75 years. We carried out a retrospective case-control study (N = 212) that included LTs with donors older than 75 years (group A, n = 106 cases) that were performed in our center between the years 2010 and 2020. This cohort has been paired off with a similar control group (group B, n = 106) whose donors were significantly younger. A survival analysis using the Kaplan-Meier model was performed. Average (SD) age of donors in group A was statistically greater than group B (A, 79.1 [3.0] years vs B, 54.4 [15.3], P <.001). There were no differences either in the average age of the recipients or in the Model for End-Stage Liver Disease score of both groups. Indications for LT were distributed equally in both groups: the most common was cellular hepatocarcinoma followed by alcohol-related cirrhosis. Survival rates for group A were 81%, 78%, and 67%, in 1, 3, and 5 years, respectively, while in group B they were 85%, 76%, and 71%, respectively, without differences found between the groups (P =.57). Using elderly liver donors is safe, achieving good outcomes in terms of short- and midterm rates of survival. [ABSTRACT FROM AUTHOR]

• Traditionally, large volumes of fresh frozen plasma (FFP) were required to correct altered conventional coagulation test in patients with end-stage liver disease. • Hydric overload caused by FFP may lead to a worsen of bleeding and, therefore, a higher transfusion requirement. This leads to an increase in hospital stay and patient morbidity. • The aim of this study is to determine the morbidity associated to the use of FFP in the intraoperative period of patients undergoing orthotopic liver transplantation. Traditionally, the administration of large volumes of fresh frozen plasma (FFP) was common during liver transplant surgery, with no improvement in the results in terms of bleeding and blood-saving. Moreover, this hydric overload caused by FFP may be harmful, leading to an increase in hospital stays and patient morbidity. The objective is to assess the morbidity associated to the use of FFP in the intraoperative period of patients undergoing orthotopic liver transplantation. The study design is an observational retrospective study, collecting data on the transplanted patients from 2010 to 2020. Acute renal failure was more frequent in the group that received FFP than in the group that did not, with a statistical difference (P =.0017). We did not find any statistical difference between the groups in terms of pulmonary complications and graft-associated thromboembolic events Transfusion of FFP requires large volumes to achieve a relevant elevation of coagulation factors. This hydric overload could justify the high incidence of renal complications found. Prothrombin complex could be an interesting alternative to FFP. Fibrinogen as a first-line therapy could correct perioperative bleeding and reduce the use of FFP. [ABSTRACT FROM AUTHOR]

• Growing demand for grafts prompts research into the factors involved in the success (understood as years of patient and graft survival) of liver transplant. • This context justifies the interest of this work, focused on analyzing the impact of 4 variables inherent to the intervention: donor, recipient, recipient survival, and implanted graft survival. The initial objective of this study is to analyze the impact on survival of the preservation solution used. Secondarily, the influence of donor age, underlying pathology, and graft ischemia time is investigated. A multicenter retrospective analytical observational study has been carried out. A population of 1822 liver transplant recipients is studied in 4 Andalusian hospitals between 1995 and 2014. Survival of the patient and graft is analyzed by groups based on the conservation solution used, the age of the donor, the pathology indicated for transplant and the ischemia time, and the relationship between the variables through a bivariate study. A descriptive and predictive multivariate analysis of the variables was performed. Comparison of the graft and patient survival functions for each preservation solution did not differ significantly. The bivariate analysis shows a significantly higher utilization of Celsior and histidine-tryptophan-ketoglutarate solution in graft loss. The comparison between donor age groups showed significant differences in favor of donor grafts younger than 50 years. In the multivariate analysis of patient and graft survival, the donor age obtained a hazard ratio of 1.008 (P <.005) with donors older than 47.6 and 47.5 years, respectively. Survival analysis between pathology groups found significant differences, not obtaining predictive power for patient or graft survival in the multivariate study. No significant differences were found in survival according to ischemia time, but there was a relationship between early graft loss and longer mean cold ischemia times up to 18 hours. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • In cDCD livers, postmortem NRP reduces biliary complications, in particular ITBL. • Postmortem NRP helps improve cDCD liver graft survival. • Use of postmortem NRP facilitates successful transplantation of older cDCD livers. Background & Aims Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD. Methods This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes. Results During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45–65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06–0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02–0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20–0.78; p = 0.008). Conclusions The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age. Lay summary This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors. [ABSTRACT FROM AUTHOR]

Obesity is one of the main growing epidemics of the last century and is responsible for many deaths worldwide. The aim of this study is to analyze the impact of the body mass index (BMI) of the recipient on survival and morbidity after liver transplantation (LT). We conducted a retrospective cohort study of all transplanted recipients in a third-level hospital between 2006 and 2018. The following donor variables were analyzed: age, sex, weight, BMI, cause of death. Additionally, the following recipient variables were analyzed: age, sex, weight, height, BMI, procedure indication. Finally, outcome variables were analyzed: postoperative complications, early mortality, graft loss, and overall survival. This study strictly complies with the Helsinki Congress and the Istanbul Declaration regarding donor source. We analyzed 825 of 837 LTs from January 2006 to December 2018. These were grouped by BMI categories: 271 (29%) normal, 322 (34.3%) overweight, and 228 (24.3%) obesity. The overall survival at 5 years was 83% in the normal group, 76% in the overweight group, and 71% in the obesity group. These differences were statistically significant (P =.027). The early mortality rate was 4.42% in the normal weight group, 6.5% in the overweight group, and 5.26% in the obesity group. No differences were found between groups in terms of postoperative complications: hemorrhagic, vascular, biliary, respiratory, hemodynamic, digestive, renal, neurologic, rebel ascites, and infections. No differences were found regarding the need for re-operation. In this study, overall survival in LT decreases as the BMI of recipient increases; but overweight and obesity do not constitute a risk factor for early morbidity and mortality in LT. [ABSTRACT FROM AUTHOR]

Liver retransplantation can be classified as urgent (when performed in the first week after the transplantation) or elective, which may be considered as early (first month post-transplantation) or late (after the first month). The time in which retransplantation takes place is determined by the cause that makes it necessary. The goal of this study is to analyze the causes and results of early retransplantation in our center. A retrospective analysis of liver retransplantations performed within the first month after the original transplantation in our center between 2007 and 2017 was carried out. The variables analyzed were demographic, causes of the first transplant and retransplantation, and the complications and mortality resulting from the latter. A total of 698 liver transplants were performed, including 67 patients who required retransplantation (8.9%). Among these, 37 were late elective retransplantations and 30 were early retransplantations. Regarding the latter, the causes that led to the first transplant were hepatocellular carcinoma (46.7%) and noncholestatic cirrhosis (30%). On the other hand, the main precipitants of the retransplantation were hepatic artery thrombosis (60%) and primary graft failure (13.3%). The reoperation rate was 16.7%, and the perioperative mortality rate was 16.7%. The 1-, 2-, and 5-year survival rates were 83.3%, 76.7% and 59.9%, respectively. Despite the high perioperative morbidity of liver retransplantation, its results in terms of survival are similar to those of the global series of liver transplantation. [ABSTRACT FROM AUTHOR]

The presence of collateral circulation in liver cirrhosis patients with portal hypertension is quite frequent due to re-permeabilization of closed embryonic channels. In some cases, these shunts could measure over 1 cm wide, therefore, containing a significative blood flow. Its management during liver transplantation could be challenging due to possible complications resulting from either ligation of the shunts or from ignoring them. We present the case of a patient with recurrent hepatic encephalopathy (HE) and a large spontaneous portosystemic shunt (SPSS) who submitted to liver transplant and review the literature identifying options, complications, and outcomes with the aim of facilitating decision making. A 68-year-old, Spanish man diagnosed with liver cirrhosis with portal hypertension and recurrent episodes of HE is proposed for LT. The patient's Child-Pugh score was A6-B7, and the Model for End-stage Liver Disease score was 12. Preoperatively, a computed tomography scan showed a large SPSS running to the inferior cava vein. During the surgery, a small-sized portal vein and a large shunt measuring almost 3 cm wide were identified. After reperfusion, portal vein flow was 1000 to 1100 mL/min. Owing to the previous HE and the risk of low portal flow, the shunt was closed increasing the portal flow to 1800 mL/min. The patient was discharged without any complications. The presence of large SPSSs are frequent during LT. Decision making intraoperatively can be challenging due to possible complications derived from ligation of the SPSS or from ignoring it. Either preoperative assessment of a further HE risk or portal vein flow measurement after reperfusion are essential to achieve a correct resolution. [ABSTRACT FROM AUTHOR]

Background & Aims There is an increasing discrepancy between the number of potential liver graft recipients and the number of organs available. Organ allocation should follow the concept of benefit of survival, avoiding human-innate subjectivity. The aim of this study is to use artificial-neural-networks (ANNs) for donor-recipient (D-R) matching in liver transplantation (LT) and to compare its accuracy with validated scores (MELD, D-MELD, DRI, P-SOFT, SOFT, and BAR) of graft survival. Methods 64 donor and recipient variables from a set of 1003 LTs from a multicenter study including 11 Spanish centres were included. For each D-R pair, common statistics (simple and multiple regression models) and ANN formulae for two non-complementary probability-models of 3-month graft-survival and -loss were calculated: a positive-survival (NN-CCR) and a negative-loss (NN-MS) model. The NN models were obtained by using the Neural Net Evolutionary Programming (NNEP) algorithm. Additionally, receiver-operating-curves (ROC) were performed to validate ANNs against other scores. Results Optimal results for NN-CCR and NN-MS models were obtained, with the best performance in predicting the probability of graft-survival (90.79%) and -loss (71.42%) for each D-R pair, significantly improving results from multiple regressions. ROC curves for 3-months graft-survival and –loss predictions were significantly more accurate for ANN than for other scores in both NN-CCR (AUROC-ANN = 0.80 vs. –MELD = 0.50; -D-MELD = 0.54; -P-SOFT = 0.54; -SOFT = 0.55; –BAR = 0.67 and -DRI = 0.42) and NN-MS (AUROC-ANN = 0.82 vs. –MELD = 0.41; -D-MELD = 0.47; -P-SOFT = 0.43; -SOFT = 0.57, -BAR = 0.61 and -DRI = 0.48). Conclusions ANNs may be considered a powerful decision-making technology for this dataset, optimizing the principles of justice, efficiency and equity. This may be a useful tool for predicting the 3-month outcome and a potential research area for future D-R matching models. [ABSTRACT FROM AUTHOR]