European Liver Transplant Centers Research Articles

Renal Replacement Therapy for Acute Kidney Injury in Severe Alcohol-Associated Hepatitis as a Bridge to Transplant or Recovery.

Acute kidney injury is seen in approximately 30% of patients with severe alcohol-associated hepatitis (AH) and is associated with increased mortality. Controversy exists surrounding initiation of renal replacement therapy (RRT) in these patients, as most are ineligible for early transplantation. The primary aim was to identify predictors of survival and identify patients who may benefit from RRT as a bridge to transplant or recovery. A retrospective multicenter cohort of adult patients with AH, who received RRT, was developed, including patients from two North American and one European liver transplant centers. Fifty-five patients were included. Survival was 26/55 (47.3%) at 30days, 17/55 (30.9%) at 3months, and 15/55 (27.2%) at 6months. Of those who survived 6months, 2/15 (13.3%) received simultaneous liver and kidney transplantation, 11/15 (73.3%) had spontaneous recovery of kidney function, and 2/15 (13.3%) remained on RRT. Of patients who survived at least 3months, 8/17 (47%) completed addiction treatment. Predictors of mortality were pre-RRT MELD (OR 1.10, 1.02-1.19) and pre-RRT MELD-Na (OR 1.14, 1.03-1.27). Pre-RRT MELD-Na < 35 was associated with lower 6-month mortality (OR 0.23, 0.06 - 0.81). Of patients with pre-RRT MELD-Na < 35, 50% survived 6months compared to 18% of patients with pre-RRT MELD-Na ≥ 35. Although RRT has a limited role in patients with decompensated cirrhosis, ineligible for transplant, it may be used in select patients with AH. This may allow for spontaneous recovery with alcohol abstinence or completion of addiction treatment prior to transplant.

Median Arcuate Ligament Compression in Orthotopic Liver Transplantation: Results from a Single-Center Analysis and a European Survey Study.

Median arcuate ligament compression (MALC) potentially causes arterial complications in orthotopic liver transplantation (OLT). Here we aimed to investigate the incidence of MALC and its impact on clinical outcome after OLT. In addition, we performed an international survey among 52 European liver transplant centers to explore local protocols on the management of these patients. Data of 286 consecutive OLT recipients from a prospective database were analyzed retrospectively (05/2010-07/2017). Preoperative computed-tomography images were evaluated. Celiac axis stenosis due to MALC was found in 34 patients (12%). Intrinsic stenosis was present in 16 (6%) patients. Twenty-six patients (77%) with MALC underwent standard arterial revascularization with median arcuate ligament (MAL)-division. Patients treated for MALC had comparable baseline data and no difference was found in early- and long-term outcome compared to the rest of our cohort. Our survey found heterogeneous strategies regarding diagnosis and treatment of MALC. Only 29% of the centers reported the division of MAL in these patients as routine procedure. Even though there is no consensus on diagnosis and management of MALC among European centers, a surgical division of MAL is feasible and safe and should be considered in OLT recipients with MALC.

Comparison of Two Questionnaires on Informed Consent in “Marginal” Donor Liver

The necessity of liver donors has contributed to overcoming the traditional criteria and to propose new ones for the acceptance of livers for transplantation. For this reason expanded or extended criteria donation (ECD) or even overextended criteria for marginal or high-risk organ donors have been developed. Ethical, Legal and Psychological Aspects of Organ Transplantation (ELPAT) and European Liver and Intestine Transplant Association (ELITA) – European Liver Transplantation Registry (ELTR) coordinated the distribution of a previously reported questionnaire that was sent to 53 European liver transplant centers. Criteria were divided based on the response rate. Donor criteria such as steatosis and serum sodium >165 mmol/L, as well as recipient criteria such as previous history of cancer, were not considered contraindications to transplantation in more than 60% of cases. Criteria such as ICU (intensive care unit) stay, body mass index >30, serum bilirubin >3 mg/dL, and HIV infection or critical illness were not considered adequate for transplantation in 30% to 59% of cases. On the other hand, there was no agreement on other extended liver donor and recipient criteria, such as age up to 80 years, serum glutamic oxaloacetic transaminase >90 U/L, serum glutamic pyruvic transaminase >105 U/L, high-risk sex practices, drug users, patients older than 65 years, and patients younger than 65 years, respectively. Criteria such as serum sodium could not be considered ECD criteria. In conclusion, development of more studies and inclusion of more liver transplantation centers are required to confirm these data.

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus (HIV) positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers. Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV positive patients with hepatitis C virus (HCV) has poorer outcomes overall, requiring careful selection of candidates. This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management. In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.

A Preliminary European Study on Extended-Criteria Liver Donation and Transplant Recipient Consent

ELPAT (Ethical, Legal, and Psychologic Aspects of Organ Transplantation) coordinated the distribution to European liver transplant centers of an electronic questionnaire regarding the definition of extended-criteria liver donation (ECD) and its implication for informed consent by transplant recipients. Completed questionnaires were received from 30 centers in 13 countries including 28 who accepted ECD liver donors. The criteria to define a liver donor as ECD were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%); serum sodium >165 mmol/L in 17 centers (60%); ICU stay with ventilation >7 days in 16 centers (57%); serum glutamic oxaloacetic transaminas >90 U/L, in 12 centres (42%); body mass index >30 kg/m2 in 10 centers (35%); serum glutamate pyruvate transaminase >105 U/L in 10 centers (35%); serum bilirubin >3 mg/dL in 10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers informed the transplant candidate of the ECD status of the donor: 10 (43%) when the patient registered for transplantation, 3 (14%) when an ECD liver became available, and 10 (43%) on both occasions. Ten centers required the liver transplant candidate to sign a special consent form. Ten centers informed the potential recipient of the donor's serology. Only 3 centers informed the potential recipient of any high-risk behavior of the donor.

Extended Criteria Liver Donation and Transplant Recipient Consent: The European Experience

The organization known as ELPAT (Ethical, Legal and Psychological Aspects of Organ Transplantation) coordinated the distribution of an electronic questionnaire concerning the definition of extended criteria liver donation (ECD) and the implication for informed consent of transplant recipients to European liver transplant centers. Completed questionnaires were received from 30 centers in 13 countries. Twenty-eight centers accepted ECD liver donors. The criteria for defining a liver donor as ECD were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%); serum sodium levels higher than 165 mmol/L in 17 centers (60%); intensive care unit stay with ventilation longer than 7 days in 16 centers (57%); serum glutamic oxalo-acitic transaminase levels higher than 90 U/L in 12 centers (42%); body mass indeces more than 30 in 10 centers (35%); serum glutamic pyruvic transaminase levels higher than 105 U/L in 10 centers (35%); serum bilirubin levels higher than 3 mg/dL in 10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers informed the transplant candidate of the ECD status of the donor: 10 centers (43%) when the patient registered for transplantation, 3 centers (14%) when an ECD liver became available, and 10 centers (43%) on both occasions. Ten centers required the liver transplant candidate to sign a special consent form. Ten centers informed the potential recipient of the donor's serology. Only three centers informed the potential recipient of any high risk behavior of the donor.

European multicenter survey on antibiotic prophylaxis in liver transplant patients

Infection remains a major problem for patients undergoing liver transplantation (LT). However, no data regarding perioperative antibiotic prophylaxis are available. The aim of the study was to gain insight into prophylactic antibiotic strategies used in European liver transplant centers.

Analysis of differences in outcome of two European liver transplant centers

Authors analyzed the differences in the outcome of two European liver transplant centers differing in case volume and experience. The first was the Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary (SEB) and the second the University Medical Center Groningen, Groningen, The Netherlands (UMCG). We investigated if such differences could be explained. The 1-, 3- and 5-year patient survival in the UMCG was 86%, 80%, and 77% compared with 65%, 56%, and 55% in SEB. Graft survival at the same time points was 79%, 71%, and 66% in the UMCG and 62%, 55%, and 53% in SEB. Significant differences were present regarding the donor and recipient age, diagnosis mix, disease severity and operation variables, per-operative transfusion rate, vascular complications, postoperative infection rate, and need for renal replacement. To determine factors correlating with survival, a separate uni- and multivariate analysis was performed in each center individually, between study parameters and patient survival. In both centers, peri-operative red blood cell (RBC) transfusion rate was a significant predictor for patient survival. The difference in blood loss can be explained by different operation techniques and shorter operation time in SEB, with consequently less time spent on hemostasis. It was jointly concluded that measures to reduce blood loss by adapting the operation technique might lead to improved survival and reduced morbidity.

APROTININ REDUCES BLOOD LOSS AND TRANSFUSION REQUIREMENTS IN ORTHOTOPIC LIVER TRANSPLANTATION: A PLACEBO-CONTROLLED MULTICENTER STUDY.

1015 Intraoperative activation of the fibrinolytic system has been shown to contribute to the bleeding tendency during orthotopic liver transplantation (OLT). Aprotinin is a serine anti-protease and a potent inhibitor of fibrinolysis. Although small, retrospective studies have suggested that aprotinin may reduce blood loss in OLT, its indication remains controversial. We initiated a prospective, double-blind, placebo-controlled multicenter study (EMSALT) to test the hypothesis that aprotinin reduces blood loss in OLT. Six European liver transplant centers (Leiden, Rotterdam, Bologna, Huddinge, Brussels, Helsinki) participated in this study. Perioperative patient management, including blood transfusion were standardized according to the study protocol. Patients were randomized to either high dose aprotinin (2×106 KIU loading dose, followed by 1×106 KIU/hr and an additional bolus of 1×106 KIU 20 min before reperfusion), regular dose (2×106 KIU loading dose, followed by 0.5×106 KIU/hr), or placebo. Randomization was performed per center. After obtaining informed consent, 137 adult patients, who underwent their first OLT and met the inclusion criteria, were randomized. There were no significant differences in demographic data or severity of disease between the three groups. Primary end-points are presented in the tableTableThrombo-embolic events were seen in 1 patient in the high dose group, none of the patients in the regular dose group, and in 3 patients in the placebo group (p=0.41). Mortality (30 days) was not different between the three groups (6.5%, 4.7% and 8.3%; p=0.79). Conclusions: This prospective study shows that aprotinin is an effective and safe drug to help reduce blood loss and transfusion requirements in patients undergoing OLT.

Prague's IKEM and Berlin's Virchow Clinic: three years of bilateral cooperation between two European liver transplant centers.

With sweeping political changes in Europe since 1989, cooperation across former borders has become possible. This article reports an experience of cooperation between an established center in Western Europe (Berlin's Virchow Clinic) and a developing center in Central Europe (Prague's Institute for Clinical and Experimental Medicine, or IKEM). The relationship began with common organ procurement and has resulted in a high-quality transplant program in the Czech Republic. The Virchow Clinic functioned as counselor, adviser, and mentor to the developing center. The cooperation was supported by Eurotransplant, and training was provided to IKEM to enhance skills for an improved national program for liver transplantation. Standards for IKEM's full membership in the northwestern European network have been met. The number of liver transplantations per million population in the Czech Republic has markedly increased since the onset of this cooperative effort.

Prague's IKEM and Berlin's Virchow Clinic: Three Years of Bilateral Cooperation between Two European Liver Transplant Centers

With sweeping political changes in Europe since 1989, cooperation across former borders has become possible. This article reports an experience of cooperation between an established center in Western Europe (Berlin's Virchow Clinic) and a developing center in Central Europe (Prague's Institute for Clinical and Experimental Medicine, or IKEM). The relationship began with common organ procurement and has resulted in a high-quality transplant program in the Czech Republic. The Virchow Clinic functioned as counselor, adviser, and mentor to the developing center. The cooperation was supported by Eurotransplant, and training was provided to IKEM to enhance skills for an improved national program for liver transplantation. Standards for IKEM's full membership in the northwestern European network have been met. The number of liver transplantations per million population in the Czech Republic has markedly increased since the onset of this cooperative effort.

Risk of HBV reinfection after liver transplantation in HBsAg‐positive cirrhosis: Primary hepatocellular carcinoma is not a predictor for HBV recurrence

Two hundred and twenty-eight patients who underwent orthotopic liver transplantation for hepatitis B-related cirrhosis in 11 European Liver Transplant Centers were collected. The male/female ratio was 184/44, with a median age of 41 years (13-66). In 55 patients (24%) hepatocellular carcinoma was associated with liver disease. All cases were stratified for pre-orthotopic liver transplantation viral characteristics: HBV-DNA neg/HBeAg neg: 106 patients (47%), HBV-DNA neg/Delta pos: 80 (35.5%), HBV-DNA pos/HBeAg pos: 28 (12.5%), other 14 (5%). In 49 patients (21.4%) post-orthotopic liver transplantation passive prophylaxis with anti-HBs immunoglobulins was not followed, while in 179 patients the anti-HBs serum titer was kept above 100-200 mU/ml. Overall 5-year actuarial survival of the series was 54%. One hundred and eighty-five patients were evaluable for HBsAg reappearance in the serum at various intervals after orthotopic liver transplantation. Overall 3-year HBV-free survival of these patients was 55%. There was a significant difference in 3-year HBV-free survival between HBV-DNA neg (52%), HBV-DNA pos (13%) and Delta pos (73%) patients (p: 0.03). Sixty-three percent of patients in the prophylaxis group were HBV-free, compared to only 25% of untreated patients (p < 0.001). Three-year HBV-free survival in patients with or without HCC was 44% and 59%, respectively. Cox-multivariate analysis revealed that only post-transplantation prophylaxis (p: 0.003) and pre-transplantation viral activity (p: 0.004) can be considered as independent factors affecting HBV recurrence. Candidates with hepatocellular carcinoma in HBV-cirrhosis should not be excluded from orthotopic liver transplantation, supporting the idea of a higher risk of post-transplantation viral reactivation.