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Background Impact of portal vein thrombosis (PVT) on the clinical course in liver transplant candidates remains unclear. This study aims to identify prevalence and risk factors for PVT, assess outcome after liver transplantation (LT) in patients with PVT and study the effect of anticoagulation. Methods This single-center retrospective cohort study was performed from January 2006 until June 2016. Patients were stratified according to presence of PVT. Risk factors and outcome were assessed using logistic regression and survival analysis. Results Among 390 adults who underwent orthotopic LT, PVT occurred in 40 (10.3%). In, respectively, 10 (25%), 7 (17.5%), and 23 (57.5%) patients, PVT was identified at time of evaluation for transplantation, on the waiting list and during transplantation. A beneficial trend was present favoring the use of anticoagulation for PVT resolution (n = 3/7 vs 0/9; p = .062). Patient and graft survival were similar between the groups after a median follow-up of 5 years. However, 1-year patient survival was significantly lower (p = .031) in patients with PVT. Conclusion Portal vein thrombosis occurred in 10% of patients awaiting LT was undiagnosed in 50% until moment of LT and had a deleterious effect on 1-year survival. Anticoagulation showed a beneficial trend on recanalization of PVT and survival rate.

INTRODUCTION: Liver transplantation (LTx) is the standard treatment for biliary atresia (BA) patients with end-stage liver disease. The prognosis after LTx has steadily improved, but overall prognosis of BA-patients is also determined by mortality before LTx. We aimed to quantify mortality in young BA-patients on the Eurotransplant waiting list and to determine the effect of disease severity and age at time of listing on pretransplant mortality.METHODS: We used a cohort study design, which incorporated data from the Eurotransplant registry. Participants were 711 BA-patients below 5 years from 5 countries and listed for LTx between 2001-2014. We applied competing risk analysis to evaluate simultaneously the outcomes death, LTx and still-waiting-for-a-suitable-organ. We used Cox proportional hazards regression to assess two-year mortality. In a sub-cohort of 416 children, we performed multivariable analyses between two-year mortality and disease severity or age, each at listing. Disease severity at listing was quantified by the Model for End-stage Liver Disease (MELD) score, which assesses bilirubin, creatinin, albumin and INR as continuous variables.RESULTS: Two-years waiting list mortality was 7.9%. Age below 6 months and MELD score above 20 points, each at listing, were strongly and independently associated with two year mortality (each p 0.001). Twenty-one per cent of infants who fulfilled both criteria did not survive the first 6 months on the waiting list.CONCLUSION: Our findings quantify mortality among young BA-patients on the waiting list and the relative importance of risk factors (age and severity of disease at listing). Our results provide both an evidence base to rationally address high mortality in subgroups and a methodology to assess effects of implemented changes, for example in allocation rules. This article is protected by copyright. All rights reserved.

To date, psychosocial outcomes after face transplantation are promising, although the impact on family relationships is less well investigated. Depressive and anxiety symptoms, resilience, spousal support, dyadic adjustment, family functioning of a patient and the partner were assessed before, and two, three and four years after the face transplantation. Most psychological, marital and family scores of both partners remained within a normative and healthy range at follow-up. Resilience, affective responsiveness, illness cognitions, physical quality of life, and family affective responsiveness and communication of the patient further improved, whereas the partner reported higher resilience and dyadic consensus at four years after transplantation. The results of this study point to positive long-term psychosocial outcomes of a blind patient and his partner after face transplantation. Practitioner points Psychological health of patient and partner remains good after face transplantation Marital and family functioning remains stable after face transplantation and may even improve Face transplantation may strengthen the resilience of the patient and the partner

A discussion of the literature concerning the impact of care pathways in the complex and by definition multidisciplinary process of organ donation following brain death. Enhancing the quality and safety of organs for transplantation has become a central concern for governmental and professional organizations. At the local hospital level, a donor coordinator can use a range of interventions to improve the donation and procurement process. Care pathways have been proven to represent an effective intervention in several settings for optimizing processes and outcomes. A discussion paper. A systematic review of the Medline, CINAHL, EMBASE and The Cochrane Library databases was conducted for articles published until June 2015, using the keywords donation after brain death and care pathways. Each paper was reviewed to investigate the effects of existing care pathways for donation after brain death. An additional search for unpublished information was conducted. Although literature supports care pathways as an effective intervention in several settings, few studies have explored its use and effectiveness for complex care processes such as donation after brain death. Nurses should be aware of their role in the donation process. Care pathways have the potential to support them, but their effectiveness has been insufficiently explored. Further research should focus on the development and standardization of the clinical content of a care pathway for donation after brain death and the identification of quality indicators. These should be used in a prospective effectiveness assessment of the proposed pathway.

Background: In patients with hepatocellular carcinoma (HCC), the outcome after liver transplantation (LT) is excellent if tumor characteristics are within the Milan criteria (MC). Expanded Asan criteria (AC) have not yet been validated in Western countries. Methods: A total of 76 patients with HCC underwent LT. Patients were divided and compared according to Milan, UCSF, and Asan criteria. Differences between pre- and post-operative assessment were evaluated. Overall survival (OS) and disease-free survival (DFS) were compared between groups. Predictors of recurrence were investigated. Results: Asan criteria provided 26% and 15% more criteria-fitting patients than MC and UCSF pre-operatively while 49% and 35% at pathological evaluation. Discrepancy between pre- and post-operative evaluation was 32% for MC, 33% for UCSF, and 18% for AC (p=0.06). After a median follow-up of 70.5months, patients exceeding MC but fulfilling Asan had comparable 5-yr OS and DFS to patients fulfilling MC (p=0.17; p=0.29). Patients exceeding UCSF but fulfilling AC had comparable 5-yr OS and DFS to patients fulfilling UCSF (p=0.26; p=0.32). Number of nodules, macro-vascular invasion, capsular invasion, and exceeding AC predicted recurrence at multivariate analysis (p=0.01, 0.03, 0.01, 0.02, respectively). Conclusions: The extension to AC allows increasing the number of patients eligible for LT without affecting OS and DFS.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome due to defective DNA inter-strand cross-link repair. Hematopoietic stem cell transplantation (HSCT) is curative for pancytopenia, but may not prevent the development of non-hematological malignancies. We describe a 26-year-old male patient with FA and Marfan syndrome who in 1994 underwent successful HSCT with bone marrow stem cells from his human leukocyte antigen (HLA)-identical sister. In 2006, three lesions in the liver were detected and resected. The three lesions all showed activation of the β-catenin pathway and were histologically characterized by a highly differentiated steatotic hepatocellular carcinoma (HCC) with remnants of the underlying adenoma from which it arose, a hepatocellular adenoma with foci of well-differentiated HCC, and a cholestatic adenoma. Risk factors for the emergence of HCC included FA itself, the use of androgens for a period of 3 years preceding HSCT and toxicity of the conditioning regimen. Because of the danger of developing additional HCC, liver transplantation was proposed, taking into consideration that immunosuppression would increase the risk of other malignancies. By using part of the liver of the sister, who already acted as bone marrow donor 13 years earlier, immunosuppression could be avoided. Liver transplantation was performed in 2007 without complication. Five years after liver transplantation the patient is doing well. This case is twofold special being the first case reporting FA co-occurring with Marfan syndrome and being the first reported case of FA treated for HCC by liver transplantation from a HLA-identical sibling donor without the use of immunosuppression.

It has been shown that an induction therapy with the monoclonal anti-interleukin-2 receptor antibody basiliximab (Simulect) is capable to reduce the incidence of acute graft rejection in adult and pediatric liver transplantation (Ltx). However, data on long-term results using basiliximab in children post-Ltx are still pending. Therefore, the objective of our study was to report on the long-term results of basiliximab induction therapy in pediatric liver transplant recipients. A total of 54 children received two single doses of basiliximab in addition to cyclosporine and prednisolone following Ltx. We analyzed the incidence of acute and chronic graft rejection that of post-transplant lymphoproliferative disease (PTLD), and patient and graft survival. The follow-up was 22-46 months. The historical control group (matched controls) consisted of 54 patients treated with a cyclosporine and prednisolone dual therapy. Patient survival was 53 of 54 in the treatment group and 51 of 54 in the controls. One patient was retransplanted in the treatment group vs. three patients in the control group. The incidence of acute graft rejection was 16.6% compared with 53.7% in the control group (p < 0.001), that of chronic rejection was comparable in both groups (one of 54 vs. one of 54). The incidence of steroid resistant rejection was four of 54 vs. six of 54 that of PTLD were one of 54 vs. zero of 54. There were no adverse effects observed, which could be related to the antibody treatment. We conclude that basiliximab provides safe and effective induction immunosuppression in pediatric liver graft recipients. Short- and even long-term results are excellent.

Background/Aims: Clinical observations suggest cancer progression after preoperative segmental portal vein occlusion, a procedure to prevent liver failure after major hepatic resections. The aim of this study was to determine whether portal occlusion induces host reactions which promote cancer invasion and angiogenesis. Methods: The rat model of portal branch ligation (PBL) was compared with partial hepatectomy (PH) and sham operation (SO) and evaluated for the expression of heat shock protein-70 (hsp70), heme oxygenase-1 (hmox1), early growth response gene-1 (Egr-1) and urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1) and receptor (uPAR). Results: Portal deprivation after PBL was associated with a regression of liver tissue to 25% of its original mass within 8 days with only modest fibrotic changes. During the progression of atrophy, there were significant inductions of hsp70-, hmox1- and Egr-1-mRNA in comparison with regenerating liver tissue. PAI-1-specific mRNA was transiently elevated at 3 – 48 h after PBL in the atrophying lobes, whereas uPA and uPAR were unaffected in comparison with PH or SO. Conclusion: Hepatic atrophy caused by PBL is associated with increased expression of genes known to promote tumor growth. These host events represent a possible explanation for the tumor progression after portal occlusion and require further evaluation.

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.

Summary This study investigated the functional impact of O-linked glycosylation of von Willebrand Factor (VWF) A1 domains on the interaction with platelet receptors. Native or mutant VWF-A1-domains were transiently overexpressed on COS-7 cells as membrane glycosylphosphatidylinositol (GPI)-anchored FLAG-tagged fusion proteins. Cytofluometric analysis assured comparable levels of A1-domain expression among native and mutant homologues as well as for different culture conditions. Expressing native VWF-A1-domains under O-linked glycosylation blocking conditions increased the platelet aggregatory responses observed for fully glycosylated forms. Utilizing a neuronal network for prediction of O-linked glycosylation of mammalian proteins, threonine (T) and serine (S) residues located in the VWF-A1-loop flanking regions – not in the loop itself – were determined to be glycosylated n-terminal at amino acids T485, S490, T492 and T493 and c-terminal at T705. Simultaneous selective charge-to-alanine mutation of S490, T492 and T493 led to gain in aggregatory responses. When compared with native forms, equivalent alterations of T485 did not dictate functional differences. Any alanine-substitution for T705 revealed a substantial loss in aggregatory effects – possibly as a result of structural desintegration of the VWF-A1-binding site for glycoprotein (GP) Ib. These data suggest specific O-linked glycosylation of the amino-terminal VWF-A1-loop-flanking region to have a negative regulatory impact on the A1-domain affinity of non-activated human VWF for human platelet-GPIb.

Pharmacokinetic studies in adult and pediatric liver transplant recipients have shown that the C(2) monitoring is superior to the traditional determination of CsA trough levels (C(0)) as an estimate of CsA exposure. However, target reference values for C(2) in very small infants have not been established yet. The objective of our study was to assess the distribution of C(2) levels in the first week following Ltx and to analyze enteral absorption of CsA for this group of patients. We documented CsA C(0) and C(2) levels in 25 infants with a body weight below 10 kg (median 6.8 kg; range 3.0-9.8 kg) in the first 7 days after Ltx. The infants had a median age at transplantation of 7 months (range 0.3-20.0 months). The underlying diagnoses were biliary atresia (n = 17), acute liver failure (n = 4), metabolic disease (n = 4). All children received CsA microemulsion (Neoral, initial 10 mg/kg/day), prednisolone, and two single doses of basiliximab as immunosuppressive drugs. The mean C(0) and C(2) levels were as follows: day 1: C(0) 77.0 +/- 39.6, C(2) 340.5 +/- 140.0 ng/mL; day 2: C(0) 135.5 +/- 53.2, C(2) 467.0 +/- 168.2 ng/mL; day 3: C(0) 146.5 +/- 70.8, C(2) 519.0 +/- 219.1 ng/mL; day 4: C(0) 168.5 +/- 55.1, C(2) 570.0 +/- 163.7 ng/mL; day 5: C(0) 156.5 +/- 38.0, C(2) 612.0 +/- 132.4 ng/mL; day 6: C(0) 177.0 +/- 41.1, C(2) 606.0 +/- 149.2 ng/mL; day 7: C(0) 174.0 +/- 27.2, C(2) 622.0 +/- 98.8 ng/mL (r = 0.82, p < 0.05). This analysis demonstrates that there is a good enteral absorption of CsA in very small children post-Ltx in the early post-operative period. Based on the C(2) levels achieved, we conclude that there is a good correlation between C(0) and C(2) levels even in very small infants.

The chimeric, monoclonal antibody basiliximab inhibits the proliferation and clonal expansion of activated T cells. To date basiliximab has been used only in combination with other immunosuppressive agents for rejection prophylaxis after solid organ transplantation. An infant underwent liver transplantion (LTx) at the age of 5 months because of biliary atresia. The primary immunosuppression consisted of cyclosporine and prednisolone. As a result of a steroid resistant rejection episode on day 26 post-LTx we had to switch the initial immunosuppressive regiment to tacrolimus and steroids. Because of severe cholestasis and assumed impaired enteral resorption we were forced to administer an unusually high dosage (2 mg/kg/day) of tacrolimus. Four months after LTx an intestinal B-cell lymphoma was diagnosed when the patient suffered from a small bowel perforation. After stopping the immunosuppressive medication we started treatment with the anti-CD20 monoclonal antibody rituximab for B-cell depletion. During the 12 wk no B cells were detectable in the peripheral blood by flow cytometry. In this setting we started a monotherapy with repetitive doses of basiliximab for immunosuppression. During the following course there was no further rejection and no recurrence of the tumor. From this experience we conclude that monotherapy with basiliximab after LTx and anti-CD20 treatment for B-cell lymphoma is efficient and safe.

Background: Data on the oxidative metabolism of polymorphonuclear neutrophils (PMN) after solid organ transplantation are very limited. We hypothesized that immunosuppressive agents reduce the capacity of PMN to produce reactive oxygen species, such as O2−, H2O2, OH, and OCL− leading to an increased susceptibility to infectious complications after liver transplantation. Methods: A lucigenin-enhanced chemiluminescence (CL) assay was used with soluble and particulate stimuli to study the oxidative metabolism of PMN in pediatric liver graft recipients. Sixteen patients (median age: 2.4 yr) were enrolled in a prospective study and integrated CL response was compared with the CL activity of 29 healthy controls. Results: In the second week post-transplant, we found a significantly reduced CL activity. Pre-operatively, and after lowering steroids and cyclosporin A (CsA) the oxidative burst was normal. Conclusions: Our data suggest that CsA and steroids may not only influence T and B cells but also PMN, which may be a relevant factor for the incidence of infectious complications in pediatric liver graft recipients.

In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3-5.7 yr after performing successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m 2 ). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m 2 ) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.

Invasive aspergillosis is one of the most severe complications after liver transplantation characterised by early dissemination of disease and high mortality. Recent data show that the prognosis is diminishing even further when Aspergillus terreus, a strain resistant to standard treatment with amphotericin, is isolated. We report a high risk liver transplant recipient with multiple co-morbidities including renal failure and allograft dysfunction in whom pulmonary aspergillosis due to A. terreus was successfully treated by the echinocandin antifungal agent caspofungin.

Hepatocyte transplantation using porous matrices is under investigation as an alternative therapy for certain liver diseases. For this purpose, long-term function of transplanted hepatocytes is mandatory. This problem has not been sufficiently investigated yet. In this study Lewis rats were used as donors and recipients. Stimulated (group A, portocaval shunt) or unstimulated (group B) hepatocytes were transplanted into prevascularized polyvinyl-alcohol matrices. Cell-free matrices served as controls (group C). Matrices were harvested between 1 h and 1 year after implantation and analyzed by morphometry; albumin RNA in situ hybridization; and cytokeratin-, actin-, desmin-, and macrophage-specific antigen immunohistology. The hepatocyte number significantly decreased within the first week following implantation. Between 1 month and 1 year after transplantation a significant increase in hepatocyte number was noted in groups A and B. Albumin transcripts of transplanted hepatocytes were at normal levels at all times except for group B after 1 year. The immunohistology suggested engraftment of nonparenchymal liver cells. We conclude that 3-dimensional matrices provide a sufficient environment for long-term engraftment of transplanted liver cells. The hepatocytes are able, despite suboptimal initial engraftment, to repopulate the scaffold for at least half of the recipient's life span and maintain cell-specific function after sufficient stimulation.

In this report, transmission of malaria via a liver, a kidney, and possibly a heart allograft from a single donor is described. The donor had immigrated from Cameroon to Germany 18 months before, but had no clinical signs of active malaria infection. The liver transplant recipient and one of the two kidney transplant patients developed febrile illness with the appearance of Plasmodium vivax in blood smears 5 and 6 wk after transplantation, respectively. In the heart transplant recipient, a subclinical malaria infection was suspected based on a rise of malaria antibodies late after transplantation, whereas the recipient of the second kidney allograft had no clinical or laboratory evidence of malaria. Both liver and kidney recipients with active malaria responded to medical treatment. However, the liver transplant patient developed progressive cholestasis and died 5 months after transplantation from liver failure possibly due to side effects of the malaria medication. Other cases of malaria in solid organ recipients are briefly reviewed.

Living donor and split-liver transplantation techniques require the calculation of a standard liver volume (SLV) as a reference point for the minimal volume necessary for the recipient. We therefore examined whether a widely used formula developed on the basis of a Japanese population sample was also adequate for the Caucasian population. The documentation of volumes of 1332 autopsy livers from a German Forensic Medicine Department was used to create a formula for an SLV for the Caucasian population. The Japanese formula estimated the Caucasian liver volume to be on average 322.6 +/- 335. 8 g (SD) less than they actually were. The following new formula for the calculation of SLV for Caucasians was established by linear regression analysis: Liver volume (mL) = 1072.8 * body surface area(m2)-345.7.

Computed tomography (CT) has proven to be of great value and preciseness in the assessment of the segmental volume, e.g., in living related liver transplantation. The incisions of the falciform ligament and the left hepatic vein are used as landmarks of the proposed dissection plane when procurement of the left lateral lobe is planned. Aside from the volume of the segment, its thickness and shape are important to determine its suitability for transplantation. Although anatomical variations of the hepatic veins are known and bear surgical consequences for anastomosis-like double orifices, their impact on volume assessment has not been recognized yet.