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BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or 1 μg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: For over 30 years, ascites has been postulated to facilitate fibrinolysis in patients with liver cirrhosis. In contrast to previous research employing conventional coagulation tests, this study aimed to characterize hemostatic interactions between blood and ascites using the rotational thromboelastometry (ROTEM). Methods: Blood samples – pure or mixed with ascites in a ratio of 1:1 – from cirrhotic patients (n = 10) were subjected to ROTEM analysis. In addition, a negative control group was built with cirrhotic patients (n = 10) whose blood was mixed with physiologic sodium chloride (0.9% NaCl) solution in a ratio of 1:1. Subsequently, ROTEM measurements were subjected to statistical analysis. Results: During ascites challenge, clotting time (CT, measured in seconds) was significantly prolonged in EXTEM (blood: 70.40 ± 20.40 vs. ascites/blood: 109.8 ± 47.7) and APTEM (blood: 66.50 ± 14.55 vs. ascites/blood: 138.7 ± 105.8), likely reflecting a dilution effect. However, CT in INTEM remained unchanged, suggesting a sustained intrinsic pathway function. Maximal clot firmness (measured in millimeters) in FIBTEM decreased significantly (blood: 14.70 ± 9.55 vs. ascites/blood: 6.00 ± 5.66), thus indicating depletion of fibrinogen in ascites. Strikingly, maximum lysis (measured in %) significantly decreased in EXTEM (blood: 9.30 ± 2.79 vs. ascites/blood: 5.50 ± 2.84), APTEM (blood: 8.50 ± 3.10 vs. ascites/blood: 5.60 ± 2.88), and INTEM (blood: 7.50 ± 2.27 vs. ascites/blood: 5.10 ± 3.48). Conclusions: ROTEM provided new evidence that ascites may not primarily induce fibrinolysis in cirrhotic patients. This finding seems to be of significant importance for the clinical management of cirrhotic patients experiencing complications, for example, abdominal hemorrhage after liver biopsy or paracentesis; here, replacement of prothrombin complex concentrates and/or fibrinogen concentrates may prove more beneficial than the use of fresh frozen plasma or antifibrinolytic drugs.

Zusammenfassung Hintergrund Der Stellenwert und die Sicherheit einer perkutanen Leberbiopsie (PLB) bei hirntoten Spendern vor Organentnahme sowie der Einfluss der PLB auf die Organallokation und die Kosten im Rahmen der Lebertransplantation (LT) in der Eurotransplant-Region (ET), werden weiterhin diskutiert. Material und Methoden Eine perkutane Leberbiopsie vor Organentnahme erfolgte bei 36 hirntoten Spendern. Die Komplikationsrate, Spendercharakteristika, Ultraschallbefunde, die makroskopische Einschätzung und die histologischen Ergebnisse der PLB wurden analysiert. Zusätzlich wurde eine landesweite Umfrage unter 11 Lebertransplantationsexperten durchgeführt. Der Bedarf einer PLB und ihre Auswirkungen auf den Prozess der Organallokation wurden evaluiert. Mögliche Kosteneinsparungen wurden für verschiedene Szenarien auf der Grundlage von Kostendaten der Deutschen Stiftung Organtransplantation berechnet. Ergebnisse Es wurden keine Komplikationen durch die PLB beobachtet. Die Umfrage ergab, dass das Ergebnis der PLB einen erheblichen Einfluss auf die Allokation von Spenderorganen hat, insbesondere bei solchen mit „extended donor criteria (EDC)“. Die Kostenberechnung ergab ein enormes Kosteneinsparungspotenzial durch eine optimierte Allokation und die Vermeidung unnötiger Organentnahmen. Schlussfolgerung Die PLB ist ein sicheres Verfahren und besitzt ein enormes Potenzial für die Optimierung der Organallokation vor Organentnahme durch eine Reduzierung der kalten Ischämiezeit, Vermeidung unnötiger Verwerfungen von Spenderorganen sowie Kosteneinsparungen. Die klinische Relevanz und der Einfluss der PLB auf die Organallokation konnte durch unsere Daten herausgestellt werden.

Primary sclerosing cholangitis (PSC) is characterized by inflammation of the whole bile duct system. Liver transplantation is only approved as a curative treatment when it comes to end-stage liver disease. The aim of our study was to assess morbidity, survival rates and PSC recurrence and the impact of donor characteristics in long-term follow-up. This was an IRB-approved retrospective study. A total of 82 patients were identified who were transplanted between January 2010 and December 2021 for PSC. Among these patients, 76 adult liver transplant PSC patients and their corresponding donors were analyzed. Three pediatric cases and three adult patients with a follow-up within 10 years (15 vs. 22, p = 0.004). Most patients (65%) passed in the first year following transplantation, with primary non-function (PNF), sepsis and arterial thrombosis being the most common causes of death. Donor characteristics did not affect patient survival. Patients with PSC show excellent 10-year survival rates. While the lab-MELD score significantly affected long term outcomes, donor characteristics did not affect survival rates.

Recent data demonstrated that amongst patients undergoing elective surgery the prevalence of cirrhosis is 0.8% equating to approximately 25 million cirrhotic patients undergoing surgery each year worldwide. Overall. the presence of cirrhosis is independently associated with 47% increased risk of postoperative complications and over two and a half-increased risk of in-hospital mortality in patients undergoing elective surgery. In particular, perioperative patients with chronic liver disease have long been assumed to have a major bleeding risk on the basis of abnormal results for standard tests of hemostasis. However, recent evidence outlined significant changes to traditional knowledge and beliefs and, nowadays, with more sophisticated laboratory tests, it has been shown that patients with chronic liver disease may be in hemostatic balance as a result of concomitant changes in both pro- and antihemostatic pathways. The aim of this paper endorsed by the Liver Intensive Care Group of Europe was to provide an up-to-date overview of coagulation management in perioperative patients with chronic liver disease focusing on patient blood management, monitoring of hemostasis, and current role of hemostatic agents.

Perioperative care of patients undergoing liver transplantation (LT) is very complex. Metabolic derangements, hypothermia, coagulopathy and thromboses, severe infections, and graft dysfunction can affect outcomes. In this manuscript, we discuss several perioperative problems that can be encountered in LT recipients. The authors present the most up-to-date information regarding predicting and treating hemodynamic instability, coagulation monitoring and management, postoperative ventilation strategies and early extubation, management of infections, and ESLD-related pulmonary complications. In addition, early post-transplant allograft dysfunction will be discussed.

Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide-mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive. In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.

Hyponatremia is a common electrolyte disorder in patients with end-stage liver disease (ESLD) and is associated with increased mortality on the liver transplantation (LT) waiting list. The impact of hyponatremia on outcomes after LT is unclear. Ninety-day and one-year mortality may be increased, but the data are conflicting. Hyponatremic patients have an increased rate of complications and longer hospital stays after transplant. Although rare, osmotic demyelination syndrome (ODS) is a feared complication after LT in the hyponatremic patient. The condition may occur when the serum sodium (sNa) concentration increases excessively during or after LT. This increase in sNa concentration correlates with the degree of preoperative hyponatremia, the amount of intraoperative blood loss, and the volume of intravenous fluid administration. The risk of developing ODS after LT can be mitigated by avoiding large perioperative increases in sNa concentration . This can be achieved through measures such as carefully increasing the sNa pretransplant, and by limiting the intravenous intra- and postoperative amounts of sodium infused. SNa concentrations should be monitored regularly throughout the entire perioperative period.

Patients with liver cirrhosis who are in need of surgery show a high in-hospital mortality. This study examined the risk of postoperative morbidity and in-hospital mortality after operations on patients with liver cirrhosis.In the time period from January 2010 to December 2017 a total of 321 patients with liver cirrhosis underwent general surgery in this department. Liver-specific scoring systems, such as the Child-Pugh score (CPS) and MELD score were retrospectively assessed and correlated with in-hospital mortality and perioperative morbidity using the Dindo-Clavien classification.Of the 321 patients (68% male) 21.2% underwent emergency surgery. These patients showed a mortality of 60%, which is significantly higher than in elective surgery (12%, p 0.0001). Complex interventions showed a 41% mortality, minor interventions still 20.5% (p = 0.0001). The postoperative complication rate and mortality were significantly different sorted by CPS with 11.8%/6.3% in the CPS A category and 84%/73% in the CPS C category, respectively (p = 0.001). Statistically in-hospital mortality was increased by 20% for every point increase in the MELD score (odds ratio, OR 1.23, p = 0.0001). The presence of hepatic decompensation had the worst prognosis.Surgical interventions in patients with liver cirrhosis are associated with a high complication rate and in-hospital mortality. The CPS and MELD scores can be used for objective risk assessment, while clinical examination for signs of hepatic decompensation is also important. Laboratory values, such as sodium and creatinine can assist the assessment.HINTERGRUND UND ZIEL DER ARBEIT: Patienten mit einer Leberzirrhose, die eine operative Behandlung benötigen, weisen eine hohe Krankenhausmortalität auf. Die vorliegende Studie untersucht die postoperative Morbidität sowie Krankenhausmortalität nach stattgehabter Operation von Patienten mit einer Leberzirrhose.Retrospektiv wurden im Zeitraum von 01/2010 bis 12/2017 321 Patienten mit einer Leberzirrhose in unserer Klinik operativ behandelt. Erfasst wurden leberspezifische Scoringsysteme wie MELD(Model of End Stage Liver Disease)- und Child-Pugh-Score (CPS), die Krankenhausletalität und die postoperative Morbidität wurden mittels der Dindo-Clavien-Klassifikation erhoben.Von den 321 Patienten (68 % männlich) wurden 21,2 % als Notfall versorgt. Die Letalität der Notfallpatienten war mit 60 % signifikant höher als die der elektiv operierten Patienten (12 %, p 0,0001). Komplexe Eingriffe zeigen insgesamt eine Letalität von 41 %, kleinere Eingriffe immer noch 20,5 % (p = 0,0001). Die postoperativen Komplikationsrate und Mortalität zeigten sich nach CPS signifikant unterschiedlich bei 11,8 % bzw. 6,3 % in der CPS-A-Kategorie im Vergleich zu 84 % bzw. 73 % in der CPS-C-Kategorie (p = 0,001). Statistisch steigt die Krankenhausletalität um etwa 20 % mit jedem MELD-Anstieg um einen Punkt (OR 1,23, p = 0,0001). Am schwerwiegendsten ist das Vorliegen einer hepatischen Dekompensation.Operative Eingriffe von Patienten mit Leberzirrhose sind mit einer hohen Komplikationsrate und Krankenhausletalität verbunden. CPS und MELD können bei der objektiven Risikoeinschätzung helfen, während auch die klinische Untersuchung auf Zeichen einer hepatischen Dekompensation von Bedeutung ist. Natrium, Kreatinin und andere Laborwerte können diese Einschätzung ergänzen.

Background. Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT). Methods. A retrospective analysis of the united network for organ sharing/organ procurement transplantation network database on pediatric LT performed between 1988 and 2016 was conducted. Hyponatremia was defined as a serum sodium of 130 mEq/L or below. Subjects were divided into 2 age groups: I (0-6 y old) and II (7-18 y old). Patient survival before and after LT, as well as graft survival, were compared in patients with and without hyponatremia. Multivariable Cox proportional hazards models were constructed for perioperative mortality. Results. Data from 6606 children were available for analysis of waiting list mortality, and 4478 for postoperative mortality. The prevalence of hyponatremia at the time of registration was 2.8% and 3.7% at the time of LT. Waiting list mortality in patients with hyponatremia was significantly higher in group I (P < 0.001) but not in group II (P = 0.09). In group I, the relative risk of mortality adjusted to pediatric end-stage liver disease score was significantly associated with hyponatremia (P < 0.001). A sodium level below 130 mEq/L (hazard ration [HR] = 1.7), younger age (group I) (HR = 2.01), and need for dialysis (HR = 2.3) were independent predictors for increased waiting list mortality. There was no difference in overall postoperative patient or graft survival related to hyponatremia. Conclusions. Hyponatremia is associated with increased waiting list mortality for pediatric LT candidates, particularly in younger children. Future studies examining incorporation of age-specific serum sodium levels into organ allocation policies in children seems warranted based on our findings. CA extern

The osmotic demyelination syndrome (ODS) is a serious neurological complication associated with the rapid correction of chronic hyponatremia and is associated with high morbidity and mortality. The incidence of ODS after liver transplantation (LT) is 0.8% to 1.4% and is higher than in the general population. Patients with end stage liver disease (ESLD) are very susceptible to ODS primarily because chronic hyponatremia is the most common electrolyte disorder in these patients. Impaired liver function also leads to disruption of astrocyte metabolism resulting in abnormalities of blood-brain barrier function and a decreased ability to generate new intracellular osmotically active compounds (osmolytes) in response to osmotic changes. LT is the only definitive treatment for hyponatremia in ESLD. Massive fluid shifts that occur intraoperatively can change serum sodium concentration (sNa) significantly. The severity of preoperative chronic hyponatremia is an important risk factor for ODS after LT. ODS after LT is most likely due to unintentional sodium administration intraoperatively. Measures to prevent ODS should cover the entire perioperative period. Chronic symptomatic hyponatremia should be carefully treated if LT is imminent. An intraoperative management strategy to minimize increases in sNa is vital and includes limiting fresh frozen plasma and cryoprecipitate administration by using concentrated clotting factors, administering hypotonic intravenous fluids and sodium-free buffering solutions, as well as using low-sodium continuous renal replacement therapy. sNa levels and urine output should be monitored frequently intraoperatively as well as postoperatively. Neurological symptoms are common after LT, and a high index of suspicion must be maintained to diagnose ODS.

Background Recently, the postoperative Model for End stage Liver Disease score (POPMELD) was suggested as a definition of postoperative graft dysfunction and a predictor of outcome after liver transplantation (LT). Aim The aim of the present study was to validate this concept in the context of extended criteria donor (ECD) organs. Patients and methods Single-center prospectively collected data (OPAL study/01/11-12/13) of 116 ECD LTs were utilized. For each recipient, the Model for End stage Liver Disease (MELD) score was calculated for 7 postoperative days (PODs). The ability of international normalized ratio, bilirubin, aspartate aminotransferase, Donor Risk Index, a recent definition of early allograft dysfunction, and the POPMELD was compared to predict 90-day graft loss. Predictive abilities were compared by receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values. Results The median Donor Risk Index was 1.8. In all, 60.3% of recipients were men [median age of 54 (23-68) years]. The median POD1-7 peak-aspartate aminotransferase value was 1052 (194-17 577) U/l. The rate of early allograft dysfunction was 22.4%. The 90-day graft survival was 89.7%. Out of possible predictors of the 90-day graft loss MELD on POD5 was the best predictor of outcome (area under the curve=0.84). A MELD score of 16 or more on POD5 predicted the 90-day graft loss with a specificity of 80.8%, a sensitivity of 81.8%, and a positive and negative predictive value of 31 and 97.7%. Conclusion A MELD score of 16 or more on POD5 is an excellent predictor of outcome in ECD donor LT. Routine evaluation of POPMELD scores might support clinical decision-making and should be reported routinely in clinical trials.

Complex alterations of the coagulation system in end stage liver disease lead to an increased risk of bleeding and mortality. In the present study, we investigated, 1. the association of pre-liver transplant rotational thrombelastometry (ROTEM&trade, ) variables with bleeding as well as 30-day-mortality and 2. the underlying pathophysiology. After approval from the local ethics committee, rotational thrombelastometry variables, conventional laboratory coagulation values, MELD score (model of end-stage liver disease), red blood cell loss, blood product use, coagulation factors, underlying disease, and demographic data were retrospectively analysed. Pre-transplant thrombelastometry clot lysis index (CLI) and MELD were the only variables associated with mortality, bleeding and blood product use, respectively. Mortality was 4.2%, when CLI was &lt, 85%, and increased to 25.7% when the CLI was &gt, 95%. Multivariate analysis including CLI and MELD score identified the CLI as an independent and the best predictor of 30-day-mortality. Interestingly, the inhibition of fibrinolysis did neither affect CLI nor the association of the variable with mortality. Thus, fibrinolysis can be excluded as the reason for low CLI values. In conclusion, low CLI values measured before the beginning of liver transplantation are associated with reduced bleeding and mortality, but do not indicate fibrinolysis.

Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors. Although the critical minimum concentration of fibrinogen to maintain hemostasis is a matter of debate, many patients with coagulopathic bleeding require fibrinogen supplementation. Among the treatment options for fibrinogen supplementation, fibrinogen concentrate may be viewed by some as preferable to fresh frozen plasma or cryoprecipitate. The authors review major studies that have assessed fibrinogen treatment in trauma, cardiac surgery, end-stage liver disease, postpartum hemorrhage, and pediatric patients. Some but not all randomized controlled trials have shown that fibrinogen concentrate can be beneficial in these settings. The use of fibrinogen as part of coagulation factor concentrate based therapy guided by point-of-care viscoelastic coagulation monitoring (ROTEM [rotational thromboelastometry] or TEG [thromboelastography]) appears promising. In addition to reducing patients' exposure to allogeneic blood products, this strategy may reduce the risk of complications such as transfusion-associated circulatory overload, transfusion-related acute lung injury, and thromboembolic adverse events. Randomized controlled trials are challenging to perform in patients with critical bleeding, and more evidence is needed in this setting. However, current scientific rationale and clinical data support fibrinogen repletion in patients with ongoing bleeding and confirmed fibrinogen deficiency.

Acute liver failure (ALF) is defined as severe hepatic dysfunction (marked transaminases elevation, detoxification disorder (jaundice and coagulopathy with international normal ratio (INR) > 1.5), the presence of hepatic encephalopathy, and exclusion of underlying chronic liver disease, and a secondary cause like sepsis or cardiogenic shock. Reasons for ALF include paracetamol and warfarin toxicity, autoimmune and viral (mainly hepatitis B and E) hepatitis, and herbal and dietary supplements. Even in terms of meticulous and careful review of the patient, around 20–30% of the reasons remains unknown. In order of its rarity, a randomized controlled trial could hardly be done. However, because of improved ICU treatment, the mortality, even in the advanced stage of ALF decreased. However, in 5–10% of the cases an emergency transplantation is required. This justifies the treatment of this patient cohort in institutions that can provide this kind of treatment.

Acute liver failure (ALF) refers to primary damage to a previously healthy liver. It is a rare disease with an incidence of about 200-500 cases/year in Germany. The liver can recover to restitutio ad integrum or lead to death in no time despite best medical treatment. Due to the rarity and potentially dramatic clinical course, patients with acute liver failure should be promptly referred to a special liver unit that can provide a liver transplantation as rescue treatment.The ALF should be strictly distinguished from "acute-on-chronic" liver failure (ACLF), which may show a similar clinical course but does not qualify for a high-urgency listing and transplantation.The reason for an ALF remains unknown in up to 20 % of cases. Hepatotropic virus (HAV, HBV and HEV) are the most common causative agents in Africa and Asia, while in North America and Northern and Central Europe, more drug-related liver failure is more frequent. Among drugs paracetamol and phenprocoumone are the leading cause for ALF. However, there are a couple of dietary supplements, herbs and mushroom poisoning that cause ALF.Other reasons are ischemic hepatitis and autoimmune hepatitis.Es ist von entscheidender therapeutischer und diagnostischer Konsequenz zwischen einem echten akuten Leberversagen und einer akuten Dekompensation einer chronischen Lebererkrankung mit oder ohne Organausfall zu unterscheiden.Ungeachtet des klinischen Eindrucks gehört ein Patient mit akutem Leberversagen zunächst auf die Intensivstation. Sofern möglich, ist eine kausale Therapie durchzuführen. Bisher existiert kein funktionierendes Leberersatzverfahren. Plasmapherese kann nützlich sein. GERINNUNGSSTöRUNG: Untersuchungen der letzten Jahre zeigen, dass beim ALV eher eine Thromboseneigung als die bisher vermutete Koagulopathie besteht. ENZEPHALOPATHIE UND HIRNöDEM: Die Enzephalopathie und ein potenziell letales Hirnödem spielen eine entscheidende Rolle für die Prognose.Bei akutem Leberversagen wird zunehmend weniger transplantiert. Dies liegt am ehesten am Fortschritt in der intensivmedizinischen Therapie.

Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management (‘theranostic’ approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient’s safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration. CA - Görlinger

This review provides insight into our current understanding of the pathophysiology and treatment of coagulopathy associated with liver failure, and bleeding risk assessment.Patients with end-stage liver disease (ESLD) have a rebalanced coagulation profile and are at risk for both excessive clotting and bleeding. Hypercoagulability is associated with profound endothelial dysfunction and an increased concentration of liver-independent coagulation factors. Because of this rebalanced coagulation profile, standard laboratory tests have been demonstrated to be ineffective in either predicting and/or guiding the management of coagulopathy. Viscoelastic testing, however, is able to provide a dynamic assessment of clot formation in whole blood and has been demonstrated to be invaluable in both monitoring and management of coagulation problems associated with liver failure. More recently, there is increasing interest in thrombin generation tests to monitor coagulation in patients with ESLD.Multiple institutional protocols for prophylaxis and treatment of ESLD-related thromboses have been developed. High-quality studies evaluating these approaches are lacking.Patients with ESLD are at risk for excessive bleeding and clotting. Treatment of any significant coagulopathy should not be based solely on standard laboratory tests. Thrombosis prophylaxis has to be considered in susceptible populations.

CA extern

Introduction Because of the shortage of available organs for renal transplantation, strategies enabling the safe use of organs from donors with potential chronic infections such as hepatitis C are necessary. The aim of this study was to analyze the outcome of renal transplant donation from hepatitis C virus (HCV)-positive donors. Methods Between September 2002 and May 2007, 51 kidneys (34 donors) reactive for HCV antibodies were further evaluated. Six kidneys (5 donors) were transplanted to 6 recipients with known chronic HCV infection. The remaining 29 donors underwent extended virological testing. Nine donors were HCV RNA positive and thus not suitable for HCV-negative patients. Twenty donors (21 kidneys) did not have detectable HCV RNA copies and were transplanted into 21 HCV-negative recipients. Clinical outcomes focusing on safety, allograft function, and de novo HCV infection in the recipient were collected. Results There were no de novo HCV infections detected in recipients who were HCV negative before transplantation. The extended virological donor screening did not have an impact on median cold ischemia time. Five-year graft survival was 75%. Discussion Organs from anti-HCV-reactive, nonviremic donors can be transplanted safely to HCV-negative recipients.

Was ist neu? Diagnosestellung Es ist von entscheidender therapeutischer und diagnostischer Konsequenz zwischen einem echten akuten Leberversagen und einer akuten Dekompensation einer chronischen Lebererkrankung mit oder ohne Organausfall zu unterscheiden. Therapie Ungeachtet des klinischen Eindrucks gehört ein Patient mit akutem Leberversagen zunächst auf die Intensivstation. Sofern möglich, ist eine kausale Therapie durchzuführen. Bisher existiert kein funktionierendes Leberersatzverfahren. Plasmapherese kann nützlich sein. Gerinnungsstörung Untersuchungen der letzten Jahre zeigen, dass beim ALV eher eine Thromboseneigung als die bisher vermutete Koagulopathie besteht. Enzephalopathie und Hirnödem Die Enzephalopathie und ein potenziell letales Hirnödem spielen eine entscheidende Rolle für die Prognose. Transplantation Bei akutem Leberversagen wird zunehmend weniger transplantiert. Dies liegt am ehesten am Fortschritt in der intensivmedizinischen Therapie.

Everolimus (EVR) is a mammalian target of rapamycin (mTOR) inhibitor commonly used for immunosuppression (IS) after liver transplantation (LT). However, there are concerns about whether mTOR inhibitors may move the hemostatic balance toward a higher likelihood of thrombosis. The present study aimed to investigate potential coagulation disorders after the administration of EVR. We evaluated 54 patients after conversion to an EVR-based IS regimen (n = 26) and compared those patients with patients who were switched to extended-release tacrolimus (TAC) but had never received EVR (n = 28). At baseline and again at 1 month and 6 months after conversion, we measured international normalized ratio, activated partial thromboplastin time, and anticoagulation and fibrinolysis factors, and we performed rotational thromboelastometry (ROTEM). Data were analyzed with a Mann-Whitney U test, a repeated-measure analysis of variance, and a Fisher's exact test. Statistical significance was set at the level of P ≤ 0.05. Plasma levels of von Willebrand factor, fibrinogen, and factor VIII were significantly higher than baseline levels at 1 month and 6 months after conversion of IS to EVR (P < 0.001); plasma levels of protein C, protein S, and plasminogen also increased significantly (P < 0.001). ROTEM confirmed a significant increase in maximum clot firmness in EXTEM, INTEM, and FIBTEM assays (P < 0.001). In all assays, maximum lysis was significantly lower than baseline levels at 1 month and 6 months after conversion to EVR. Patients converted to IS with extended-release TAC exhibited no significant changes in coagulation variables. Retrospective analysis showed a significantly higher incidence of thromboembolic complications among patients treated with EVR-based IS than among those treated with extended-release TAC (P < 0.01). In conclusion, the administration of EVR after LT seems to modify hemostasis to a procoagulant state. Thrombophilia screening before conversion may determine which patients will benefit from conversion to EVR-based IS.

BACKGROUND Vasoplegia is a clinical condition typically manifested by cardiovascular instability unresponsive to the usual doses of inotropes or vasopressors. It can occur in a variety of clinical settings including liver transplantation (LT). Immunoglobulins have been used to treat sepsis-related vasoplegia. We performed a retrospective study to evaluate the efficacy of IgM-enriched immunoglobulin (IgMIg) on 30-day mortality and its ability to reverse vasoplegia in patients undergoing LT. METHODS Between May 2013 and November 2017, 473 LT were performed at our institution. We identified 21 patients who received IgMIg for 3 days to treat vasoplegia. Patients included in the study met the criteria for having vasoplegia and required noradrenaline administration greater than 1 μg·kg·min for more than 24 hours to maintain a mean arterial pressure of 70 mm Hg or greater. Procalcitonin and interleukin-6 (IL-6) levels were used as surrogate markers for inflammation and were measured at the beginning and end of IgM treatment. RESULTS After IgMIg administration, median noradrenaline infusion rates could be significantly reduced from 1.6 μg·kg·min (1.3-2 μg·kg·min) to 0.16 μg·kg·min (0.08-0.34 μg·kg·min) (P < 0.001). In addition, after treatment, procalcitonin levels decreased significantly from 44 ng/mL (24-158) to 26.1 ng/mL (10.9-48.7) (P < 0.001) and IL-6 levels decreased significantly from 63 pg/mL (29-102) to 20 pg/mL (11-20) (P < 0.001). Thirty-day morality was 14.3%. CONCLUSIONS The administration of IgMIg in patients with vasoplegia after LT is associated with a return of hemodynamic stability. Despite a predicted mortality of over 90% by Sepsis-Related Organ Failure Assessment score, the mortality rate of patients receiving IgMIg in our study was less than 20%.

Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease that affects up to 30% of patients with cirrhosis [1]. Intrapulmonary vascular dilatations and shunts result in gas exchange abnormalities, ranging from elevated alveolar-arterial oxygen gradients with no hypoxemia to very severe hypoxemia [1, 2]. Currently, liver transplantation (LT) is the only treatment option [3]. The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing liver disease severity that has been validated to predict the 3-months waitlist mortality, and is used by Eurotransplant for prioritising allocation of liver transplants [4]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Raevens has nothing to disclose. Conflict of interest: Dr. Rogiers has nothing to disclose. Conflict of interest: Dr. Geerts has nothing to disclose. Conflict of interest: Dr. Verhelst has nothing to disclose. Conflict of interest: Dr. Samuel has nothing to disclose. Conflict of interest: Dr. van Rosmalen has nothing to disclose. Conflict of interest: Dr. Berlakovich has nothing to disclose. Conflict of interest: Dr. Delwaide has nothing to disclose. Conflict of interest: Dr. Detry has nothing to disclose. Conflict of interest: Dr. Lehner has nothing to disclose. Conflict of interest: Dr. Mittler has nothing to disclose. Conflict of interest: Dr. Nadalin has nothing to disclose. Conflict of interest: Dr. Nevens reports grants from Roche, grants from Astellas, grants from Sandoz, grants and other from BMS, grants and other from CAF, grants and other from MSD, grants and other from TwinPharma, grants and other from Ipsen, other from Gilead, other from Novartis, other from Abbvie, other from Promethera Biosciences, other from Durect, other from Ferring, other from Gore, other from Cook medical, other from Biotest, other from Intercept, outside the submitted work. Conflict of interest: Dr. Pirenne has nothing to disclose. Conflict of interest: Dr. Saner has nothing to disclose. Conflict of interest: Dr. Schneeberger reports other from Merck, other from Astellas, grants and other from Chiesi, other from Teva, other from Novartis, grants from Sandoz, outside the submitted work. Conflict of interest: Dr. Stippel has nothing to disclose. Conflict of interest: Dr. Zoltan has nothing to disclose. Conflict of interest: Dr. Troisi has nothing to disclose. Conflict of interest: Dr. Van Vlierberghe has nothing to disclose. Conflict of interest: Dr. COLLE reports other from PROMETHERA, outside the submitted work. Conflict of interest: Dr. TURK JEROVSEK has nothing to disclose.

BACKGROUND: This retrospective UNOS database evaluation analyzes the prevalence of preoperative portal vein thromboses (PVT), and postoperative thromboses leading to graft failure in pediatric patients undergoing liver transplantation (LT). METHODS: The evaluation was performed in three age groups: I (0–5), II (6–11), III (12–18) years old. Factors predictive of pre- and postoperative thromboses were analyzed. RESULTS: Between 2000 and 2015, 8982 pediatric LT were performed in the US. Of those, 390 patients had preoperative PVT (4.3%), and 396 (4.4%) had postoperative thromboses. The prevalence of both types of thromboses was less in Group III than in the other two groups (3.20% vs 4.65%, p = 0.007 and 1.73% vs. 5.13%, p < 0.001, respectively). The prevalence of postoperative thromboses was significantly higher in Group I than in the other two groups (5.49% vs. 2.51%, p < 0.001). Preoperative PVT was independently associated with postoperative thromboses (OR = 1.7, p = 0.02). Children less than 5 years of age were more likely to develop postoperative thromboses leading to graft failure (OR = 2.9, p < 0.001). CONCLUSION: Younger children undergoing LT are prone to pre-and postoperative thrombotic complications. Preoperative PVT at the time of transplantation was independently associated with post-operative thromboses. Perioperative antithrombotic therapy should be considered in pediatric patients undergoing LT.