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Introduction: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands. Methods: In this nationwide, retrospective observational study, all patients (age < 18 years) diagnosed with a malignant liver tumour, who underwent partial liver resection or orthotopic liver transplantation (OLT) between January 2014 and April 2021, were included. Children with a malignant liver tumour who were not eligible for surgery were excluded from the analysis. Data regarding tumour characteristics, diagnostics, treatment, complications and survival were collected. Outcomes included major complications (Clavien–Dindo ≥ 3a) within 90 days and disease-free survival. The results of the HB group were compared to those of a historical HB cohort. Results: Twenty-six children were analysed, of whom fourteen (54%) with HB (median age 21.5 months), ten (38%) with HCC (median age 140 months) and one with sarcoma and a CNSET. Thirteen children with HB (93%) and three children with HCC (30%) received neoadjuvant chemotherapy. Partial hepatic resection was possible in 19 patients (12 HB, 6 HCC, and 1 sarcoma), whilst 7 children required OLT (2 HB, 4 HCC, and 1 CNSET). Radical resection (R0, margin ≥ 1.0 mm) was obtained in 24 out of 26 patients, with recurrence only in the patient with CNSET. The mean follow-up was 39.7 months (HB 40 months, HCC 40 months). Major complications occurred in 9 out of 26 patients (35% in all, 4 of 14, 29% for HB). There was no 30- or 90-day mortality, with disease-free survival after surgery of 100% for HB and 80% for HCC, respectively. Results showed a tendency towards a better outcome compared to the historic cohort, but numbers were too small to reach significance. Conclusion: Survival after surgical treatment for malignant liver tumours in the Netherlands is excellent. Severe surgical complications arise in one-third of patients, but most resolve without long-term sequelae and have no impact on long-term survival. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome. Methods: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity. Results: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18‐70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30‐day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later. Conclusions: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%). [ABSTRACT FROM AUTHOR]

Summary: Due to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD‐reLT with three DBD‐reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD‐reLT were compared with 63 matched DBD‐reLTs. Donors in the DCD‐reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m2, P‐value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD‐reLT was significantly higher (38.1% vs. 12.7%, P‐value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether distinct trajectories of anxiety and depression exist among liver transplant candidates, and to gain insight into demographic, clinical, and individual characteristics related with these trajectories.Design: A multicentre, prospective cohort study among 216 liver transplant candidates. Respondents filled out a questionnaire at study entrance and subsequently every 6 months until transplantation or removal from the waiting list.Methods: Anxiety (STAI6), depression (CES-D), demographic, and individual variables were assessed by questionnaire. Clinical variables were retrieved by medical record review. The SAS PROC TRAJ procedure was used to identify distinct trajectories. Univariate and multiple ordinal logistic regression analyses were used to explore related variables.Results: Regarding anxiety, three stable trajectories were identified as follows: below clinical level (51%), slightly above clinical level (34%), and high above clinical level (15%). Regarding depression, four stable trajectories were identified as follows: below clinical level (23%), slightly below clinical level (34%), slightly above clinical level (28%), and high above clinical level (6%). For anxiety as well as for depression, experiencing more liver disease symptoms, a lower level of personal control, making more use of emotional coping, and making less use of task-oriented coping increased the likelihood of membership in those trajectories with higher symptom levels.Conclusion: Distinct, but stable, trajectories of anxiety and depression were present in liver transplant candidates. The trajectories with symptom levels above clinical relevant levels for anxiety or depression comprised, respectively, 49% and 34% of the respondents. Therefore, psychological screening and subsequently providing appropriate interventions are warranted early in the transplant process. Statement of contribution What is already known on this subject For transplant candidates, the waiting-list period is a period of uncertainty and unpredictability. Psychological problems, such as anxiety and depression, are common among liver transplant candidates. Several demographic, clinical, and individual characteristics are associated with anxiety and depression, but these results remain inconclusive. What does this study add Distinct trajectories of symptoms of anxiety and depression are present among liver transplant candidates. Given the stability of the trajectories over time, the symptom level at baseline is indicative of the symptom level during the waiting-list period. Experiencing more liver disease symptoms, low mastery, more use of emotional coping, and less use of task-oriented coping are associated with trajectories of high symptom levels. [ABSTRACT FROM AUTHOR]

Background Liver transplantation with livers grafts from elderly donors has been associated with a higher risk of biliary complications. The aim of this study was to examine whether our national protocol could contribute to a lower incidence of biliary complications. Methods All adult recipients in the Netherlands transplanted with a liver from an elderly donor (≥65 yrs; n = 68) in the period January 2000-July 2011 were matched with recipients of a liver from a donor <65 yr (n = 136). Outcome parameters were 90-d, one-yr, and three-yr patient/graft survival rates, biliary complications (non-anastomotic stricture, anastomotic stricture, biliary leakage, and post-transplant cholangitis), and postoperative hepatic ischemic injury serum markers ( AST/ ALT). Results The median cold ischemia time (CIT) was 7:25 (h:min) in the group recipients of an elderly donor liver graft. Ninety-day, one-yr, and three-yr patient/graft survival rates were similar between the group with an elderly donor liver and their younger controls. Moreover, no differences were found in the incidence of biliary complications and postoperative levels of AST/ ALT between the two groups. Conclusion Transplantation of livers from elderly donors (≥65 yr) is not associated with a higher incidence of biliary complications, in a national policy wherein the CIT is kept short. [ABSTRACT FROM AUTHOR]

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS-CoV-2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

In the Netherlands, the average quality of donor organs continues to decrease as a result of the increasing life expectancy, as well as higher incidence of obesity, diabetes mellitus, and other comorbidities in the general population. Storing donor organs on ice, the current standard practice, appears to be inadequate for preserving these high-risk donor livers. Consequently, an increasing number of donor organs is discarded for transplantation. Over the past years, a novel dynamic preservation technique using a machine perfusion device has been developed. Preservation by machine perfusion enables optimisation and viability testing of high-risk donor livers prior to liver transplantation. A large proportion of initially declined donor livers appeared to be suitable for transplantation after evaluation during machine perfusion. Testing of donor livers has led to a significant increase in the number of liver transplantations performed in the Netherlands. This technique has the potential for use in other organs, such as kidney allografts.

Background and Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome., Methods: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity., Results: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18-70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30-day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later., Conclusions: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%)., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

There is a shortage of donor livers from deceased persons, which means there is a relatively high mortality rate among patients on the national liver-transplant waiting list in the Netherlands. This justifies expanding the current programme for liver transplants from living donors. The new law on donor organs law came into effect on 1 July 2020. The expectation is that this will lead to a greater supply of post-mortem donor livers. New methods for organ preservation could also lead to an increase in the number of available donor livers. An increase in the supply of donor livers could lead to changes in donor policy. These changes should take into consideration that a liver transplant from a living donor can take place earlier in the course of the disease and that the quality of the donor liver is better, which means that outcomes for the recipient are also better.

Due to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD-reLT with three DBD-reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD-reLT were compared with 63 matched DBD-reLTs. Donors in the DCD-reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m 2 , P-value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD-reLT was significantly higher (38.1% vs. 12.7%, P-value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background:  Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) are serious causes of morbidity and mortality after pediatric liver transplantation. To reduce thrombotic complications, routine antithrombotic therapy consisting of 1 week heparin followed by 3 months acetylsalicylic acid, was implemented in our pediatric liver transplant program in 2003. This study aimed to evaluate incidences of bleeding and thrombotic complications since the implementation of routine antithrombotic therapy and to identify risk factors for these complications., Methods:  This retrospective cohort study includes 200 consecutive pediatric primary liver transplantations performed between 2003 and 2016. Uni- and multivariate logistic regression analysis, Kaplan-Meier method, and Cox regression analysis were used to evaluate recipient outcome., Results:  HAT occurred in 15 (7.5%), PVT in 4 (2.0%), and venous outflow tract thrombosis in 2 (1.0%) recipients. Intraoperative vascular interventions (odds ratio [OR] 14.45 [95% confidence interval [CI] 3.75-55.67]), low recipient age (OR 0.81 [0.69-0.95]), and donor age (OR 0.96 [0.93-0.99]) were associated with posttransplant thrombosis. Clinically relevant bleeding occurred in 37%. Risk factors were high recipient age (OR 1.08 [1.02-1.15]), high Child-Pugh scores (OR 1.14 [1.02-1.28]), and intraoperative blood loss in mL/kg (OR 1.003 [1.001-1.006]). Both posttransplant thrombotic (hazard ratio [HR] 3.38 [1.36-8.45]; p  = 0.009) and bleeding complications (HR 2.50 [1.19-5.24]; p  = 0.015) significantly increased mortality., Conclusion:  In 200 consecutive pediatric liver transplant recipients receiving routine postoperative antithrombotic therapy, we report low incidences of posttransplant vascular complications. Posttransplant antithrombotic therapy seems to be a valuable strategy in pediatric liver transplantation. Identified risk factors for bleeding and thrombotic complications might facilitate a more personalized approach in antithrombotic therapy., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Liver retransplantation (re-LT) accounts for up to 22% after primary liver transplantation (LT), and using donor livers for retransplantation can only be justified by successful outcomes., Methods: A total of 2,387 adult recipients with 2,778 LT, between 1979 and 2017, were analyzed to determine risk factors and outcome of re-LT in the Netherlands., Results: Of 2,778 LT, 336 (12.1%) were first, 43 (1.5%) were second, and 12 (0.5%) were third or fourth re-LT. The 5-year patient survival for primary LT, and first, second, and third or fourth re-LT were 74.0%, 70.8%, 63.3%, and 57.1%, respectively (P = 0.10). Recipient age (≤60 years) (OR 1.96, P < 0.001), era (1979-2006) (OR 1.56, P = 0.003), donor after circulatory death (DCD) (OR 1.96, P < 0.001), and cold ischemia time (CIT) (>9 h) (OR 1.42, P = 0.007) were significant risk factors for retransplantation after primary LT., Conclusions: Recipient age, era, DCD, and prolonged CIT were identified as parameters for retransplantation. The outcome after the first re-LT was good, and comparable to those of primary transplants. Survival after multiple re-LT was not significantly different from the first retransplant group, legitimizing third and fourth re-LT to well-selected patients., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Introduction: In the past decades, short-term results after solid organ transplantation have markedly improved. Disappointingly, this has not been accompanied by parallel improvements in long-term outcomes after transplantation. To improve graft and recipient outcomes, identification of potentially modifiable risk factors and development of biomarkers are required. We provide the rationale and design of a large prospective cohort study of solid organ transplant recipients (TransplantLines)., Methods and Analysis: TransplantLines is designed as a single-centre, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. Data will be collected from transplant candidates before transplantation, during transplantation, at 3 months, 6 months, 1 year, 2 years and 5 years, and subsequently every 5 years after transplantation. Data from living organ donors will be collected before donation, during donation, at 3 months, 1 year and 5 years after donation, and subsequently every 5 years. The primary outcomes are mortality and graft failure. The secondary outcomes will be cause-specific mortality, cause-specific graft failure and rejection. The tertiary outcomes will be other health problems, including diabetes, obesity, hypertension, hypercholesterolaemia and cardiovascular disease, and disturbances that relate to quality of life, that is, physical and psychological functioning, including quality of sleep, and neurological problems such as tremor and polyneuropathy., Ethics and Dissemination: Ethical approval has been obtained from the relevant local ethics committee. The TransplantLines cohort study is designed to deliver pioneering insights into transplantation and donation outcomes. The study design allows comprehensive data collection on perioperative care, nutrition, social and psychological functioning, and biochemical parameters. This may provide a rationale for future intervention strategies to more individualised, patient-centred transplant care and individualisation of treatment., Trial Registration Number: NCT03272841., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma., Methods: We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 μmol/L [2·9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243., Findings: From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3·67, 95% CI 1·15-11·69; p=0·03). Three of the 11 deaths among patients in the percutaneous transhepatic biliary drainage group occurred before surgery. The proportion of patients with severe preoperative drainage-related complications was similar between the groups (17 [63%] patients in the percutaneous transhepatic biliary drainage group vs 18 [67%] in the endoscopic biliary drainage group; relative risk 0·94, 95% CI 0·64-1·40). 16 (59%) patients in the percutaneous transhepatic biliary drainage group and ten (37%) patients in the endoscopic biliary drainage group developed preoperative cholangitis (p=0·1). 15 (56%) patients required additional percutaneous transhepatic biliary drainage after endoscopic biliary drainage, whereas only one (4%) patient required endoscopic biliary drainage after percutaneous transhepatic biliary drainage., Interpretation: The study was prematurely stopped because of higher all-cause mortality in the percutaneous transhepatic biliary drainage group. Post-drainage complications were similar between groups, but the data should be interpreted with caution because of the small sample size. The results call for further prospective studies and reconsideration of indications and strategy towards biliary drainage in this complex disease., Funding: Dutch Cancer Foundation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The aims of the study were to examine whether distinct trajectories of anxious and depressive symptoms are present among liver transplant recipients from before transplantation to 2 years afterward, to identify associated demographic, clinical, and individual characteristics, and to examine the influence of distinct trajectories on outcomes., Methods: A prospective, multicenter cohort study was performed among 153 liver transplant recipients. Data were retrieved using questionnaires administered before transplantation and at 3, 6, 12, and 24 months after transplantation. Clinical data were retrieved by medical record review. Latent class growth analysis was used to identify distinct trajectories. χ test, analyses of variance, and multinomial logistic regression were used to identify associated variables and the impact of the distinct trajectories on outcomes., Results: Three distinct trajectories for symptoms of anxiety (State-Trait Anxiety Inventory-short form) as well as depression (Center for Epidemiological Studies Depression Scale) were identified: "no symptoms," "resolved symptoms," and "persistent symptoms." The trajectories of persistent anxiety and depression comprised, respectively, 23% and 29% of the transplant recipients. Several clinical and individual variables were associated with the trajectories of persistent anxiety and/or depression: experiencing more adverse effects of the immunosuppressive medication, lower level of personal control, more use of emotion-focused coping, less disclosure about the transplant, and more stressful life events. The trajectories of persistent symptoms were associated with worse outcomes regarding medication adherence and health-related quality of life, but not with mortality., Conclusions: A significant subset of transplant recipients showed persistent symptoms of anxiety and depression from before to 2 years after transplantation. These results emphasize the importance of psychosocial care in the transplant population.

Background: In the Netherlands, anonymity of organ donation, which is currently protected by legislation, has come under discussion. In the Dutch society, a tendency to allow direct contact between transplant recipients and their donor's family is noticeable. As little is known about the opinion of Dutch liver transplant recipients on anonymity of organ donation and direct contact with the donor's family, this study examines their opinions., Methods: A cross-sectional study was conducted in 244 liver transplant recipients. Their opinions were examined in relation to demographic, transplant-related and emotional variables. Data were collected by questionnaire. Transplant-related variables were retrieved from the hospital's liver transplant database., Results: Fifty-three percent of the respondents (n = 177) agreed with anonymity of organ donation, mainly out of respect for the donor. Living situation, age, and level of positive affect influenced this opinion. The majority of the respondents (65%) indicated that they would like to receive some information about their donor, like age, sex, and health status. Only 19% of the respondents favored direct contact with the donor's family, mainly to express their gratitude personally. Respondents transplanted for alcoholic cirrhosis were less in favor of direct contact. Respondents with feelings of guilt doubted more about direct contact., Conclusion: There is no need to change the current legislation on anonymity of organ donation. However, most liver transplant recipients would like to receive some general information about their donor. Therefore, clear guidelines on the sharing of donor data with recipients need to be established.

After liver transplantation, recipients often experience psychological problems that are influenced by demographic, personal, and transplant-related variables. However, because previous studies have mostly reported on psychological problems and their influencing factors in the first years after transplantation, less is known about their prevalence and influence in the long run. The aims of this study were to examine point-prevalence rates of symptoms of anxiety, depression, and posttraumatic stress (PTS) at different time periods after transplantation and to examine the transplant-related variables associated with these problems. A cross-sectional survey was performed among 373 liver transplant recipients who received transplants between 1979 and 2009 at our center. Five clinically relevant time periods were identified: 0.5 to <2 years, 2 to <5 years, 5 to <10 years, 10 to <15 years, and ≥15 years after transplantation. The response rate was 75% (n=281). Overall, 33.4% of the respondents experienced clinically relevant symptom levels of anxiety (28.7%), depression (16.5%), or PTS (10.0%). Symptoms of anxiety and depression were more prevalent in the first 2 years and in the long term after transplantation. PTS symptoms were more prevalent in the first 5 years after transplantation. However, the prevalence rates did not differ significantly between time periods. Viral hepatitis and the number of side effects of the immunosuppressive (IS) medication were found to be associated with all psychological problems. Alcoholic liver disease was associated with anxiety and depression in the short term after transplantation. In conclusion, a significant subset of transplant recipients experience psychological problems, both shortly after transplantation and in the long run. These problems are often associated with side effects from the IS medication. Therefore, the monitoring of psychological problems, the offering of psychological counseling, and the management of the medication's side effects should be part of the routine care of transplant recipients., (© 2015 American Association for the Study of Liver Diseases.)

Background: Livers with moderate (30-60%) macrovesicular steatosis have been associated with poor outcome after transplantation. Aim of this study was to examine the outcome after transplantation of livers with moderate macrovesicular steatosis when the cold ischemia time (CIT) is kept very short., Methods: Postoperative outcome of 19 recipients of a moderate steatotic liver were compared with a matched control group of 95 recipients of a nonsteatotic liver graft (1:5 ratio). We studied graft/patient survival rates, incidences of primary nonfunction, postoperative complications (classified according to the Clavien-Dindo classification), first-week postoperative hepatic injury serum markers (AST/ALT), and liver function tests (PT time/bilirubin/lactate). In addition, we studied reversal of graft steatosis in follow-up biopsies., Results: Median CIT in livers with moderate steatosis and in controls was below 8 h in both groups. Although short- and long-term patient/graft survival rates and results of liver function tests were similar, serum markers of hepatic injury and postoperative complications (especially grade IVa) were significantly higher in recipients of a moderate steatotic liver. Reversal of steatosis was seen in 9 of the 11 (82%) recipients with follow-up liver biopsies., Conclusion: Despite the association with severe postoperative complications, moderate macrovesicular steatotic livers can be used successfully for transplantation if the CIT is kept very short., (© 2014 Steunstichting ESOT.)

Purpose: To investigate the course of life of young adults diagnosed with biliary atresia (BA) in infancy by comparing patients who did and did not underwent transplantation with an age-matched Dutch reference group., Methods: All patients from the Dutch BA registry, aged >18 years, were invited to complete the course of life questionnaire., Results: Forty patients participated (response = 74%). Twenty-five had not undergone transplantation; 15 had undergone orthotopic liver transplantation. One significant between-group difference was found, namely in substance use and gambling. BA patients who underwent transplantation reported less use than the reference group (p = .01, moderate effect size). Additional moderate effect sizes were found for differences in psychosexual and social development and antisocial behavior. Patients who underwent transplantation had lower scores than one or both other groups., Conclusions: Development of BA survivors who did not undergo transplantation seems not delayed, whereas that of transplanted patients does seem somewhat delayed. However, patients who underwent transplantation display less risk behavior. Larger samples are necessary to confirm these findings., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The role of the immune system in the pathogenesis of nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) is unclear. A loss-of-function mutation in the CC chemokine receptor 5 (CCR5-Δ32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells., Aim: To investigate the impact of the CCR5-Δ32 mutation on the development of NAS., Methods: In 384 OLTs, we assessed the CCR5 genotype in donors and recipients and correlated this with the occurrence of NAS., Results: The CCR5-Δ32 allele was found in 65 (16.9%) recipients. The cumulative incidence of NAS at 5 years was 6.5% in wild-type (Wt) recipients vs 17.2% for carriers of the CCR5-Δ32 allele (P<0.01). In recipients with CCR5-Δ32, 50% of all NAS occurred >2 years after OLT, compared with 10% in the Wt group. In multivariate regression analysis, the adjusted risk of developing NAS was four-fold higher in recipients with CCR5-Δ32 (P<0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Δ32 (relative risk 5.4, 95% confidence interval 2.2-12.9; P<0.01). Donor CCR5 genotype had no impact on the occurrence of NAS., Conclusions: Patients with the CCR5-Δ32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Δ32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Δ32. These data suggest that the immune system plays a critical role in the development of NAS after OLT., (© 2010 John Wiley & Sons A/S.)

Background: To evaluate outcomes of surgical treatment in patients with hepatic metastases from renal-cell carcinoma in the Netherlands, and to identify prognostic factors for survival after resection. Renal-cell carcinoma has an incidence of 2,000 new patients in the Netherlands each year (12.5/100,000 inhabitants). According to literature, half of these patients ultimately develop distant metastases with 20% involvement of the liver. Resection of renal-cell carcinoma liver metastases (RCCLM) is performed in only a minority of patients. Hence, little is known about outcome of resectable RCCLM., Methods: Patients were retrieved from local databases of the Netherlands Task Force for Liver Surgery (14 centers) and from the Dutch collective pathology database. Survival and prognostic factors were determined by Kaplan-Meier analysis and log rank test., Results: Thirty-three patients were identified who underwent resection (n = 29) or local ablation (n = 4) of RCCLM in the Netherlands between 1990 and 2008. These patients comprise 0.5% to 1% of the total population of patients diagnosed with RCCLM in that period. There was no operative mortality. The overall survival at 1, 3, and 5 years was 79, 47, and 43%, respectively. Metachronous metastases (n = 23, P = 0.03) and radical resection (n = 19, P < 0.001) were statistically significant prognosticators of overall survival. Size < 50 mm (n = 18, P = 0,54), solitary metastases (n = 19, P = 0.93), and presence of extrahepatic metastases (n = 11, P = 0.28) did not have a statistically significant impact on survival., Conclusions: The favorable 5-year survival rate of 43% without operative mortality as found in this nationwide study indicates that selected patients with RCCLM can benefit from surgical treatment.

Unlabelled: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates., Conclusion: We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Between November 1982 and March 2006, 67 children with body weight < or =10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one-, three-, five-, and 10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty-four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0-7.0), the cut-off point for significantly different graft survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight < or =10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome.

Background/aims: The purpose of this study was to investigate whether differences existed in demography and outcome after resection for hepatocellular carcinoma (HCC) in patients with a normal liver compared to patients with a diseased liver., Methodology: Twenty-seven Caucasian patients with HCC in a histologically proven normal liver (NL group) in the Netherlands and 141 Asian patients with HCC in a diseased liver (DL group) in Japan underwent a curative liver resection. Patient and tumor characteristics, post-resectional disease-free, overall survival rates and pattern of recurrence were investigated., Results: HCC's in the NL group were found to be larger, in a more advanced stage and needed more extended resections compared to HCC's in the DL group. Microvascular invasion was similar in both groups, while capsule formation was observed less in the NL group. Overall survival and disease-free survival after curative resection were not statistically different between both groups. Also even after stratification for T-stage, there was no difference in survival. Although the rate of recurrence was similar in both groups, a significantly higher number of extrahepatic metastases was observed in the NL group., Conclusions: Distinct demographic differences existed between patients with HCC in the NL group compared to patients in the DL group. Extrahepatic recurrences were more frequent after curative resection for HCC in a normal liver. No difference in survival was demonstrated between both groups.