Risk factors for central bile duct injury complicating partial liver resection.

BACKGROUND: Bile duct injury is a serious complication following liver resection. Few studies have differentiated between leakage from small peripheral bile ducts and central bile duct injury (CBDI), defined as an injury leading to leakage or stenosis of the common bile duct, common hepatic duct, right or left hepatic duct. This study analysed the incidence, risk factors and consequences of CBDI in liver resection. METHODS: Patients undergoing liver resection between 1990 and 2007 were included in this study. Those having resection for bile duct-related pathology or trauma, or after liver transplantation were excluded. Characteristics and outcome variables were collected prospectively and analysed retrospectively. RESULTS: There were 19 instances of CBDI in 462 liver resections (4·1 per cent). One-third of patients with CBDI required surgical reintervention and construction of a hepaticojejunostomy. Resection type (P < 0·001), previous liver resection (P = 0·039) and intraoperative blood loss (P = 0·002) were associated with an increased risk of CBDI. Of all resection types, extended left hemihepatectomy was associated with the highest incidence of CBDI (2 of 9 procedures). CONCLUSION: Patients undergoing extended left hemihepatectomy or repeat hepatectomy were at increased risk of CBDI.

[Diagnostics and treatment of cholangiocarcinoma]. / Diagnostiek en behandeling van het cholangiocarcinoom.

--Cholangiocarcinoma is a rare malignancy originating from the biliary epithelium. The disease can arise anywhere in the biliary tract: intrahepatic, perihilar or distal. The overall prognosis for cholangiocarcinoma is poor. --The treatment necessitates a multidisciplinary approach. --Radical resection of the extrahepatic bile ducts, usually in combination with concomitant partial liver resection, remains the only curative treatment. --Liver transplantation in combination with neoadjuvant chemoradiation therapy seems to be promising in a highly selected group of patients. --Palliative treatment should be targeted at adequate biliary drainage, preferably by stenting. --Radiotherapy and systemic chemotherapy are not standard treatment and should be applied in an experimental setting only. --New options such as photodynamic therapy and tyrosine kinase inhibitors are promising, but still experimental treatments.

Heme oxygenase-1 genotype of the donor is associated with graft survival after liver transplantation.

Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver transplantation. Inducibility of HO-1 is modulated by a (GT)(n) polymorphism and a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short (GT)(n) allele and the A-allele have been associated with increased HO-1 promoter activity. In 308 liver transplantations, we assessed donor HO-1 genotype and correlated this with outcome variables. For (GT)(n) genotype, livers were divided into two classes: short alleles (<25 repeats; class S) and long alleles (> or =25 repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA) expression was correlated with genotypes. Graft survival at 1 year was significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%, p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT-genotype had significantly higher serum transaminases after transplantation and hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers (p = 0.03). No differences were found for any outcome variable between class S and LL-variant of the (GT)(n) polymorphism. Haplotype analysis confirmed dominance of the A(-413)T SNP over the (GT)(n) polymorphism. In conclusion, HO-1 genotype is associated with outcome after liver transplantation. These findings suggest that HO-1 mediates graft survival after liver transplantation.

Liver transplantation: an update.

Liver transplantation has been an accepted treatment for end-stage liver disease since the 1980s. Currently it is a highly successful treatment for this indication. The aim of this review is to give a general update on recent developments in the field of liver transplantation. In the last decades considerable progress has been made in the care of liver transplant candidates and recipients. At present the one- and five-year patient survival rates are approximately 85 and 75%. The indications for liver transplantation are shifting and the number of absolute contraindications is decreasing. In the coming years, an increase in the number of transplant candidates can be expected. An important problem is the shortage of donor organs, for which many solutions are being explored. A recently introduced method for recipient selection is the MELD score using simple laboratory measurements. Perioperative care at the present time is characterised by a high degree of standardisation and rapidly declining blood loss during transplantation. Long-term care includes awareness and management of recurrent disease. Important causes of morbidity and mortality such as de novo malignancies and cardiovascular disease should be adequately screened for and managed. With the increasing success of liver transplantation, physicians should aim at reaching a normal life expectancy and quality of life for transplant recipients.

The impact of aprotinin on renal function after liver transplantation: an analysis of 1,043 patients.

Renal dysfunction is frequently seen after orthotopic liver transplantation (OLT). Aprotinin is an antifibrinolytic drug which reduces blood loss during OLT. Recent studies in cardiac surgery suggested a higher risk of postoperative renal complications when aprotinin is used. The impact of aprotinin on renal function after OLT, however, is unknown. In 1,043 adults undergoing OLT, we compared postoperative renal function in patients who received aprotinin (n = 653) or not (n = 390). Using propensity score stratification (C-index 0.82) and multivariate regression analysis, aprotinin was identified as a risk factor for severe renal dysfunction within the first week, defined as increase in serum creatinine by >or= 100% (OR = 1.97, 95% CI = 1.14-3.39; p = 0.02). No differences in renal function were noted at 30 and 365 days postoperatively. Moreover, no significant differences were found in the need for renal replacement therapy (OR = 1.52, 95% CI = 0.94-2.46; p = 0.11) or in 1-year patient survival rate (OR = 1.14, 95% CI = 0.73-1.77; p = 0.64) in patients who received aprotinin or not. In conclusion, aprotinin is associated with a higher risk of transient renal dysfunction in the first week after OLT, but not with a higher need for postoperative renal replacement therapy or an increased risk of mortality.

Intraoperative blood transfusion requirement is the main determinant of early surgical re-intervention after orthotopic liver transplantation.

Liver transplantation is the treatment of choice in selected patients with end-stage liver disease. Postoperative complications often require surgical re-intervention. This study is a retrospective single-centre study to assess the incidence and type of surgical re-intervention during the in-hospital period after liver transplantation and to identify predictors of this re-intervention. From 1994 to 2002, 231 consecutive adult liver transplantations were performed. Re-intervention was classified as biliary, vascular, bleeding, septicaemia, re-transplantation or as miscellaneous. One hundred and thirty-nine surgical re-interventions were performed in 79 of 231 patients (34%). Septicaemia (44%) and bleeding (27%) were the most frequent indications for re-intervention, followed by biliary (10%) re-intervention. Vascular re-intervention, re-transplantation, and re-intervention for miscellaneous reasons, were performed in 7% each. Of all analysed variables (gender, age, diagnosis, acute liver failure, Child-Pugh classification, Karnofsky score, previous abdominal surgery, creatinine clearance, prothrombin time, anti-thrombin, platelet count, surgical technique, cold ischaemia time, warm ischaemia time, functional anhepatic time, anatomic anhepatic time, revascularisation time, year of transplantation, aprotinin administration, transfused platelet concentrate, and red blood cell transfusion requirements), only the number of transfused red blood cell concentrates (RBCs) was identified as a predictor of surgical re-intervention. Median RBC transfusion requirement during liver transplantation was 2.9 l (range 0-18.8 l) in the re-intervention group compared with 1.5 l (range 0-13.4 l) in the non-re-intervention group (P<0.001). This study revealed intraoperative blood loss as the main determinant of early surgical re-intervention after liver transplantation and emphasises the need for further attempts to control blood loss during liver transplantation.

Portal and systemic serum growth factor and acute-phase response after laparotomy or partial hepatectomy in patients with colorectal liver metastases: a prognostic role for C-reactive protein and hepatocyte growth factor.

BACKGROUND: Growth factors play a role in wound healing and tumour growth. The aim of this study was to compare the effect of partial hepatectomy (PH) and laparotomy on serum levels of growth factors and acute-phase proteins in patients with colorectal liver metastases and to correlate these levels with prognosis after PH. METHODS: Epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin like growth factor-I (IGF-I), insulin, interleukin-6 (IL-6), C-reactive protein (CRP) and serum amyloid-A (SAA) were determined in portal and systemic serum in 24 PH patients and 9 laparotomy patients. RESULTS: No differences were found in the clinicopathological characteristics of PH and laparotomy patients with the exception of the number of metastases, blood loss and operation time. The response of SAA, CRP and IGF-I was lower in PH patients than in laparotomy patients (P < 0.02). PH was associated with a higher IL-6 (P = 0.02) and HGF (P = 0.055) response than laparotomy. A higher HGF and CRP response was associated with a poorer prognosis. Total IGF-I was negatively correlated with the resected liver volume (r = -0.48, P < 0.05). CONCLUSIONS: PH is associated with a lower acute-phase and total IGF-I response and a higher HGF and IL-6 response compared with laparotomy. HGF and CRP responses had an influence on the prognosis.

The value of prospective monitoring of Epstein-Barr virus DNA in blood samples of pediatric liver transplant recipients.

UNLABELLED: Post-transplant lymphoproliferative disease (PTLD) is one of the major causes of morbidity and mortality in transplantation patients. A primary Epstein-Barr virus (EBV) infection is a major risk factor for developing PTLD. The aim of this study was to determine circulating EBV DNA after liver transplantation in pediatric patients in relation to primary EBV infection and development of PTLD. EBV serology was performed before transplantation. Every 4 weeks after transplantation a competitive quantitative polymerase chain reaction (PCR) assay for EBV nuclear antigen-1 was performed in 13 patients. Patients were followed for development of a PTLD. Before transplantation four patients were EBV seropositive and nine patients were EBV seronegative. In one of the four patients who were EBV seropositive before transplantation, EBV DNA became detectable after transplantation, with a peak load of 3600 copies/mL. None of these four patients developed a PTLD. Eight of the nine patients who were EBV seronegative before transplantation developed positive EBV DNA samples. EBV DNA was first detected at a mean of 64 days after transplantation (range 38-89). The mean peak EBV DNA load was 79,700 copies/mL (3600-446,000). Two of these patients developed PTLD, but they could not be identified based on prior or concomitant EBV PCR results. CONCLUSIONS: In pediatric liver transplantation EBV DNA load is higher in patients with a primary infection than in patients who were EBV seropositive before transplantation. The EBV PCR cannot be used to identify individual patients who develop PTLD. However, elevated EBV DNA load can be used to detect a group of patients at increased risk for PTLD.

[Resection of liver metastasis: higher chance of survival]. / Resectie van levermetastasen: hogere kans op overleving.

In patients with colorectal liver metastases, resection is the only intentionally curative therapy. It is stated that follow-up after a resection of primary colorectal malignancies does not favourably influence patient outcome. However, follow-up can identify 12% of patients with isolated liver metastases in whom liver resection should be performed. One third of these patients can be cured by liver surgery. In general, medical care is provided for lower chances of survival and freedom of disease. Local ablative therapies are probably useful, but need to be evaluated in a randomised trial. Tumour progression of hepatocellular carcinomas in patients, during the long waiting time for liver transplantation, necessitates the use of radiofrequency ablation. Minimally invasive techniques for liver resections seem to be promising but need to be evaluated before they can be more widely applied.

Liver metastasis as a first sign of fallopian tube carcinoma and the role of positron emission tomography in preoperative diagnosis.

The search for an unknown primary tumour is often time-consuming, costly and unrewarding. Positron emission tomography might be an effective method for screening the body for malignant deposits. We present the case of a woman with a symptomatic liver tumour of unknown origin. Several investigations did not reveal a primary tumour, but PET scanning showed a hot spot in the pelvis, suggesting either a primary tumour or a metastatic deposit. During operation, a primary Fallopian tube carcinoma was detected. Histopathological examination of the resected liver tumour revealed a metastasis of the Fallopian tube carcinoma. This case report demonstrates that PET scanning can be useful in the diagnostic process in patients with unknown primary tumour, and that a symptomatic liver tumour can be the first sign of Fallopian tube carcinoma.

Pylorus-preserving pancreatoduodenectomy: influence of a Billroth I versus a Billroth II type of reconstruction on gastric emptying.

BACKGROUND/AIM: Delayed gastric emptying (DGE) is a frequent problem after pylorus-preserving pancreatoduodenectomy. Important risk factors are the presence of intra-abdominal complications. Searching for other causes, this study evaluates the influence of the type of reconstruction after a pancreatoduodenectomy (Billroth I vs. Billroth II; B I vs. B II on DGE. METHODS: A retrospective study was performed evaluating consecutive patients from two surgical institutes. 174 patients were included (B II type of reconstruction n = 123, period 1992-1996; B I type of reconstruction n = 51, period 1988-1998). DGE was defined by gastric stasis requiring nasogastric intubation for 10 days or more or the inability to tolerate a regular diet on or before the 14th postoperative day. RESULTS: After a B I type of reconstruction, there was significantly longer nasogastric intubation period as compared with a B II type of reconstruction (B I median 13 days, range 4-47, B II median 6 days, range 1-40; p < 0.05). There was no difference in postoperative commencement of a normal diet. Also significantly more patients had DGE after a B I (76%) as compared with a B II type of reconstruction (32%; p < 0.05). CONCLUSIONS: The results of this study indicate a significantly higher incidence of DGE after a B I type of reconstruction as compared with a B II type reconstruction. The etiology remains speculative.

Rat liver slices as a tool to study LPS-induced inflammatory response in the liver.

BACKGROUND/AIMS: Inflammation in the liver is a complex interaction between parenchymal and non-parenchymal cells, and therefore can not be studied in vitro in pure cultures of these cells. METHODS: We investigated whether Kupffer cells in the liver slice are still responsive to an inflammatory stimulus of lipopolysaccharide (LPS), and evoke an inflammatory response in the hepatocytes. RESULTS: TNFalpha, IL-1beta and IL-10 were significantly elevated in culture medium of LPS-stimulated rat liver slices. Nitric oxide (NO) production of LPS-treated slices gradually increased from 5 to 24 h (24 h: 81+/-5 microM vs. 14+/-2 microM in control P < 0.05), paralleled by inducible nitric oxide synthase (iNOS) in the hepatocytes, iNOS mRNA was induced after 3 h. NO production but not iNOS induction was significantly inhibited by NOS inhibitors S-methylisothiourea and N(G)-nitro-L-arginine methylester. Both pentoxifylline and dexamethasone inhibited TNFalpha and IL-1beta production, albeit to a different extent, iNOS induction and, as a result thereof, NO production. CONCLUSIONS: These results imply that non-parenchymal cells in liver slices are viable and can be activated by LPS. In addition, it is concluded that the upregulation of iNOS in hepatocytes by LPS is caused by cytokines produced by Kupffer cells because inhibition of TNFalpha and IL-1beta production attenuated iNOS induction.

Superior diagnostic strength of combined contrast enhanced MR-angiography and MR-imaging compared to intra-arterial DSA in liver transplantation candidates.

To evaluate the diagnostic value of combined contrast enhanced MRA (ce-MRA) and MRI compared to that of intra-arterial DSA (i.a.DSA) in liver transplantation, transjugular porto-systemic (TIPSS) and spleno-renal shunt candidates. 50 patients in the workup for liver transplantation underwent ce-MRA/MRI and i.a.DSA within a three days interval. Both examinations were assessed with respect to vessel anatomy and patency of the arterial, portal venous, porto-systemic collateral and systemic venous system. The results were compared with the intra-operative findings when available. Malignancy detection in ce-MRA/MRI and i.a.DSA were compared. There are no significant differences for the arterial part of the vascular supply to the liver that is important for transplantation. Although the differences for the portal system are not significant, the difference between the two techniques is of clinical importance because i.a.DSA failed to detect portal vein occlusion in 4 patients. Ce-MRA is significantly better for the detection of collaterals (p < 0.001) and the assessment of the inferior vena cava, the hepatic and the renal veins (p < 0.001). Although the detection of liver malignancy is poor in both techniques, ce-MRA/MRI is superior to i.a.DSA. This study shows that a one step diagnostic approach with a combination of ce-MRA and MRI is a valuable radiological tool with a superior diagnostic strength compared to i.a.DSA in the liver transplantation and shunt candidate. Therefore, ce-MRA/MRI should replace i.a.DSA in these patients groups.

An effective treatment of severe intractable bleeding after valve repair by one single dose of activated recombinant factor VII.

IMPLICATIONS: The successful treatment with recombinant factor VIIa of a patient experiencing intractable bleeding after cardiac surgery is described.

Recombinant human interleukin-6 induces hepatocyte growth factor production in cancer patients.

BACKGROUND: Experiments in animals demonstrate an important role for interleukin-6 (IL-6) in liver regeneration. It is suggested that IL-6 initiates hepatocyte growth factor (HGF) synthesis. METHODS: The aim of the study was to examine the effect of exogenously administered recombinant human IL-6 (rhIL-6), in doses of 0.5, 1.0, 2.5, 5, 10 and 20 micrograms/kg/day, on HGF serum levels in humans. Serum HGF levels were measured on days 1, 2, 3, 8 and 15 and were correlated with serum amyloid A (SAA) and C-reactive protein (CRP). RESULTS: Median HGF levels increased to 124% at day 3 (P < 0.05) and 157% (P < 0.05) at day 8 as compared to 100% levels at day 1. An IL-6 dose-dependent increase in HGF was found at day 8 (R = 0.53, P < 0.02). The percentual change in serum HGF level at day 8 correlated with IL-6 serum levels at day 1 R = 0.59, P < 0.01). HGF levels did not correlate with CRP and SAA. CONCLUSION: In humans, rhIL-6 administration resulted in an increase in serum HGF levels.

Expression of anti-OV6 antibody and anti-N-CAM antibody along the biliary line of normal and diseased human livers.

Following hepatic injury, proliferation of anastomosing ductules can be observed. The origin of this ductular reaction is not completely clear, although there is considerable evidence for proliferation of a putative hepatic progenitor cell, reported to be located in the canals of Hering (CoH) and showing morphologic similarities with rat oval cells. In this study, we analyzed the immunophenotype of solitary oval cell-like cells (SOC), intralobular groups of cuboidal cells that might represent lining cells of CoH, bile ductular cells (BDC), bile duct epithelial cells (BEC), and hepatocytes. We used the antibodies OV6, CK19, and CD56 (NCAM) in a double-staining method in a series of 111 liver specimens. The series consisted of a variety of liver diseases, primary liver tumors, and normal livers. In normal livers, SOC, CoH, BDC, and BEC were uniformly and predominantly CK19+, OV6+, and CD56-. In diseased livers SOC and BDC were CK19+, OV6+, and also CD56+. Occasionally, BEC was CD56+ in damaged bile ducts in diseased liver, e.g., PSC. CoH lining cells were not present in cirrhotic nodules and were indistinguishable from BDC in the fibrous septa. The consistent and uniform staining patterns of SOC, CoH, and BDC support the concept that these cells share the same biliary lineage and might represent one biliary structure. The expression of CD56 on these cells in diseased livers indicates that CD56 is a useful marker for a reparative or regenerative state of the biliary liver-cell constituents but not to discriminate a putative hepatic stem cell.

Rapid decreases in donor-specific cytotoxic T lymphocyte precursor frequencies and graft outcome after liver and lung transplantation.

BACKGROUND: A decrease in donor-specific T cell precursor frequencies as seen late, one or more years, after transplantation is assumed to reflect transplantation tolerance, a condition important for long term acceptance of the allograft. However, such late decreases also occur in recipients that developed chronic transplant dysfunction questioning its relevance in transplantation tolerance. We investigated whether early, i.e., the first 6 months, decreases in donor-specific T cell precursor frequencies reflect transplantation tolerance and predict graft outcome after liver and lung transplantation. METHODS: Donor and third party specific cytotoxic (CTLp) and helper T lymphocyte precursor (HTLp) frequencies were analyzed in pretransplant and 1 (or 2) and 6-month blood samples taken from liver and lung recipients and were correlated with graft outcome. RESULTS: In liver allograft recipients with good graft function (n=7), mean donor-specific CTLp frequencies decreased as early as 1 month after transplantation and remained low thereafter. In contrast, mean CTLp frequencies did not decrease in liver allograft recipients with chronic transplant dysfunction (n=6). In lung allograft recipients, donor-specific CTLp frequencies remained relatively high and frequencies were not different between recipients without (n=6) or with (n=6) chronic transplant dysfunction. Donor-specific HTLp frequencies did not change significantly after liver or lung transplantation and did not differ between recipients without or with chronic transplant dysfunction. CONCLUSIONS: An early decrease in donor-specific CTLp correlates with good graft outcome after liver transplantation. Such rapid decreases in alloreactivity do not occur after lung transplantation illustrating the unique capacity of liver allografts to induce transplantation tolerance.

Comparison of outcome after pediatric liver transplantation for metabolic diseases and biliary atresia.

UNLABELLED: Metabolic diseases (MD) are the second largest indication group for orthotopic liver transplantation (OLTx) in children after biliary atresia (BA). A better outcome after transplantation can be expected because of a better pretransplant condition and the absence of previous abdominal surgery. To prove this statement, patient survival, graft survival, and morbidity were compared between a group of 24 for MD and 52 for BA consecutively transplanted children. The actuarial one- and five-year patient survival rates for MD were 96% and 84%, and for BA 84% and 70%, respectively (p logrank test = 0.17). Three MD children (13%) and 15 BA children (29%) died. The actuarial one- and five-year graft survival rates for MD were 75% and 58%, and for BA 75% and 64%, respectively (p logrank test = 0.76). Seven MD children (29%) and 11 BA children (21%) were retransplanted. Postoperative bleeding and gastrointestinal complications occurred less frequent (4% vs. 18% and 4% vs. 14%, respectively), whereas biliary complications, viral infections, and acute rejection occurred more frequently (38% vs. 21%, 29% vs. 15%, and 50% vs. 37%, respectively) in MD children. The difference in the incidence of the various postoperative complications between both groups was not statistically significant. The mean ICU and ventilator stay was 7.5 and four days, respectively, in MD children and 16 and 10 days, respectively, in BA children (p = ns). The mean infection, complication, intervention, and retransplantation rate was equal in both groups. CONCLUSION: Mortality and morbidity after pediatric liver transplantation for MD and BA are not different despite the better starting point for children with MD.

Serum response of hepatocyte growth factor, insulin-like growth factor-I, interleukin-6, and acute phase proteins in patients with colorectal liver metastases treated with partial hepatectomy or cryosurgery.

BACKGROUND/AIMS: The aim of the study was to compare the serum response of regeneration factors and acute phase proteins in patients treated with partial hepatectomy or cryosurgery. METHODS: The responses of serum hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I) (free and total), interleukin-6 (IL-6) and the acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA) were examined in patients with colorectal liver metastases treated with partial hepatectomy (n = 14) or cryosurgery (n = 10). RESULTS: In both groups, IL-6 peak levels at the end of the operation were followed by peak levels at day 1 for HGF and CRP. SAA peak levels occurred on day 1 (hepatectomy group) and on day 4 (cryo group). The total HGF, IGF-I, and IL-6 responses were comparable in both groups. CRP and SAA responses were higher in the patients treated with cryosurgery than in patients after hepatectomy. Free IGF-I trough levels were lower in partial hepatectomy patients than in cryosurgery patients. CONCLUSIONS: In patients with colorectal liver metastases the responses of the regenerating factors HGF, IGF-I, and IL-6 are comparable to those in patients treated with partial hepatectomy. Upregulation of acute phase protein production is higher in patients after cryosurgery than in patients after partial hepatectomy.

Retransplantation of the liver in children.

BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.