Is M30 staining a reliable marker predicting graft rejection and fibrosis in protocolar liver biopsies in post-liver transplant pediatric patients?

BACKGROUND: Liver transplantation is currently a treatment of choice in patients with end-stage liver disease. Acute cellular rejection (ACR), antibody-mediated rejection (AMR), and chronic rejection (ChR) are major causes of graft injury. Therefore, new markers predicting graft rejection are investigating. Apoptosis has been recently proposed as one of the mechanisms contributing to liver fibrosis in liver grafts. Coarse needle liver biopsy is still a gold standard in monitoring post-transplant pathologies. The aim of this study was to assess the utility of immunohistochemical (IHC) staining for M30 (cytokeratin 18), as a prognostic marker of rejection in pediatric recipients of liver transplant and predicting marker of liver fibrosis and worse follow-up. METHODS: The study enrolled 55 biopsies from 55 patients aged 2.37 to 18.9 years (median 13.87 years) who underwent protocolar liver biopsies taken 1-17 years after liver transplantation (median 8.36 years). The control group (positive control group) consisted of 26 biopsies from 16 patients in whom acute ACR was diagnosed. IHC staining for M30 (cytokeratin 18) and histochemical Azan staining were performed in all liver specimens. The following changes were re-evaluated in each specimen: features of ACR (the severity was assessed using RAI/Rejection Activity Index/Scale, which ranges from 3-9 points and include 3 histopathological changes suggestive of rejection), AMR or ChR; severity of fibrosis (Ishak Scale); presence of cholestasis and steatosis. Clinical parameters including laboratory tests of liver function (AST, ALT, GGTP, bilirubin) were also evaluated. RESULTS: M30 expression correlated with presence of acute cellular rejection. However, no relationship was found between M30 expression and severity of fibrosis. CONCLUSIONS: M30 staining, marker of apoptosis, seems to be a promising marker predicting acute cellular rejection.

Case Report: Liver as a Source of Hematopoietic Stem Cells After Liver Transplantation Following Hematopoietic Stem Cell Transplantation.

We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient's death 6 months after OLT. The liver can act as a clinically significant source of hematopoietic stem cells, and the liver donor's young age must be emphasized as potentially predisposing to this phenomenon. Transfer of OLT hematopoietic stem cells may not have clinical significance unless the patient is not immunocompetent or develops liver-transplantation associated GVHD, that can result in lymphocyte mediated elimination of original hematopoiesis. Patients with preexisting immunity disorder (such as primary or secondary immunodeficiency) might require intensified immunosuppressive therapy in peritransplant period as a prevention of liver-transplantation associated GVHD. Close monitoring of hematopoietic chimerism after OLT is warranted in patients at risk, because cytopenia or OLT hematopoiesis can reflect subclinical GVHD and further studies are necessary to elucidate this phenomenon.

Liver Histopathology in Late Protocol Biopsies after Pediatric Liver Transplantation.

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03-17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)-we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5-6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests.

Non-Hodgkin lymphoma after liver and kidney transplantation in children. Experience from one center.

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) is a complication of organ transplantation and a life-threatening condition. Children who underwent organ transplantation are at risk of developing lymphoproliferative disorders and, among them, non-Hodgkin lymphoma (NHL) is the most serious. OBJECTIVES: The objective of this study was to describe the clinical course of NHL after liver and kidney transplantation. MATERIAL AND METHODS: Retrospective analysis of medical records of children who underwent liver/kidney transplantation and developed NHL. RESULTS: Nine children were identified, all girls, 6 after liver and 3 after kidney transplantations. Age at transplantation ranged from 1 year to 13 years (median: 4 years), while age at lymphoma diagnosis from 4 to 17 years (median: 12 years). Time from transplantation to lymphoma diagnosis ranged from 7 months to 12 years (median: 9 years). All but 1 patient developed mature B-cell lymphoma, 4 children - diffuse large B-cell lymphoma (DLBCL), 2 children - Burkitt's lymphoma, 1 child - mature B-cell leukemia, 1 child - Burkitt-like lymphoma, while 1 patient was diagnosed with T-cell lymphoblastic lymphoma. High levels of Epstein-Barr virus (EBV) DNA were found in blood of 3 patients, and EBV in tissue samples was detected in 4 patients. Six patients presented with stage III and 2 with stage IV disease. Two patients had graft involvement. Three children received chemotherapy according to R-CHOP, 3 LMB protocol (2 with addition of rituximab), while 1 received CHOP and 5 courses of COP. T-cell lymphoma patient was treated with Euro-LB protocol. Six out of 8 treated patients are alive with a median follow-up of 6 years. Two children died from disease progression during treatment and 1 from cerebral herniation before starting therapy. All patients experienced at least 1 toxic episode of grade 3 and 4 according to Common Toxicity Criteria Adverse Event (CTCAE). Complications of chemotherapy were manageable and there were no transplanted organ failures. CONCLUSIONS: Our study provides further data on the treatment and outcome of monomorphic PTLD and indicates that it is feasible to treat solid organ recipients with multiagent chemotherapy.

Acute liver failure in children-Is living donor liver transplantation justified?

OBJECTIVES: Living donor liver transplantation (LDLT) in patients with acute liver failure (ALF) has become an acceptable alternative to transplantation from deceased donors (DDLT). The aim of this study was to analyze outcomes of LDLT in pediatric patients with ALF based on our center's experience. MATERIAL AND METHODS: We enrolled 63 children (at our institution) with ALF who underwent liver transplantation between 1997 and 2016. Among them 24 (38%) underwent a LDLT and 39 (62%) received a DDLT. Retrospectively analyzed patient clinical data included: time lapse between qualification for transplantation and transplant surgery, graft characteristics, postoperative complications, long-term results post-transplantation, and living donor morbidity. Overall, we have made a comparison of clinical results between LDLT and DDLT groups. RESULTS: Follow-up periods ranged from 12 to 182 months (median 109 months) for LDLT patients and 12 to 183 months (median 72 months) for DDLT patients. The median waiting time for a transplant was shorter in LDLT group than in DDLT group. There was not a single case of primary non-function (PNF) in the LDLT group and 20 out of 24 patients (83.3%) had good early graft function; 3 patients (12.5%) in the LDLT group died within 2 months of transplantation but there was no late mortality. In comparison, 4 out of 39 patients (10.2%) had PNF in DDLT group while 20 patients (51.2%) had good early graft function; 8 patients (20.5%) died early within 2 months and 2 patients (5.1%) died late after transplantation. The LDLT group had a shorter cold ischemia time (CIT) of 4 hours in comparison to 9.2 hours in the DDLT group (p<0.0001). CONCLUSIONS: LDLT is a lifesaving procedure for pediatric patients with ALF. Our experience showed that it may be performed with very good results, and with very low morbidity and no mortality among living donors when performed by experienced teams following strict procedures.

Polish Experience with Liver Transplantation and Post-Transplant Outcomes in Children with Urea Cycle Disorders.

BACKGROUND Liver transplantation (LT) is recommended for various metabolic diseases, including urea cycle disorders (UCDs). The aim of this study was to determine indications and outcomes of LT for UCDs in the tertiary reference Children's Hospital in Warsaw, Poland. MATERIAL AND METHODS Medical charts of children with UCD who underwent LT between 2008 and July 2016 were retrospectively reviewed. The following parameters were analyzed: symptoms at time of diagnosis, age at diagnosis, age at transplantation, graft characteristics and survival, postsurgical complications, and biochemical and laboratory results before and after transplantation. RESULTS Twelve patients with UCD who underwent LT at a mean age of 5 y (0.5-14 y) received a total of 14 liver grafts. Four children (33%) received a living donor graft, while 8 (68%) got a deceased donor liver graft. A total number of transplanted organs consisted of 9 (64%) whole-liver grafts and 5 (36%) reduced-size grafts. The 30-day post-transplant patient survival rate was 100% and graft survival rate was 93% (13/14). For those with a post-transplant follow-up of at least 1 year (n=10/12), the 1-year patient survival rate was 100% and the graft survival rate was 85.7% (12/14). Median peak of blood ammonia at presentation was 653 (159-2613) µg/dL (normal <80 µg/dl), and median peak of blood glutamine was 1273.2 µmol/l (964-3900 µmol/l). There was 1 episode of hyperammonemia following LT, but it was not due to UCD. Six (50%) patients were diagnosed with some degree of developmental delay/neurological impairment before transplantation, which remained stable or slightly improved after transplantation. Patients without developmental delay before transplantation maintained their cognitive abilities at follow-up. CONCLUSIONS LT leads to eradication of hyperammonemia, withdrawal of dietary restrictions with low-protein diet, and potentially improved neurocognitive development.

Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature.

Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.

Lipid metabolism and oxidative stress in children after liver transplantation treated with sirolimus.

Lipid disturbances are one of the most frequent side effects of SRL; however, clinical consequences are not known. The aim of the study was to evaluate the risk of AS in children after LTx treated with SRL. In 17 children with median age 13.2 yr (1.9-17.9) who received SRL on average for 4.1 yr (s.d. ± 2.9) we measured and compared with age-matched healthy control group (n = 45) lipid parameters and markers of AS: ADMA, oxyLDL, GSH, GPx, TC, TG, HDL cholesterol, LDL cholesterol, VLDL cholesterol, ApoAI, ApoB, ApoE, lipoprotein (a) (Lp(a)). We found no major differences in cholesterol, cholesterol in lipoprotein fractions and TG concentrations between patients receiving SRL and the control group. ApoE was markedly increased in the study group (19.1 g/L [±1.8]) when compared to controls (9.8 [±3.9]). ApoA1 was decreased in the study group: 1.30 g/L (±0.2) vs. 1.45 (±0.25), p = 0.04. ApoB and Lpa concentrations were similar in both groups. There were differences in oxidative stress markers: GSH 743 (±66.2) mol/mL vs. 780 (±48.2), p = 0.02 and GPx 32.8 (±5.5) U/gHb vs. 34.3(±2.6), p = 0.01. Markers of AS: ADMA did not differ between groups and oxidized LDLc was significantly lower in SRL group: 190 mU/mL (±113) vs. 237 (±107) in control, p < 0.05. SRL does not significantly disturb lipid metabolism and oxidative status in children after LTx.

The impact of cytokine gene polymorphisms on Epstein-Barr virus infection outcome in pediatric liver transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) is associated with most cases of the post-transplant lymphoproliferative disorders developed during the first year after transplantation. The high EBV DNA load constitutes a major risk for the development of EBV-related lymphoproliferations. However, among transplant recipients there are patients with a chronically high viral load (CHVL) who do not develop lymphoproliferations. The polymorphism within cytokine genes might influence the susceptibility to, and contribute to the pathogenesis of the disease. OBJECTIVES: The aim of this study was to analyze the genetic polymorphism in the selected cytokines with regard to EBV infection outcome in children after liver transplantation (LTx). STUDY DESIGN: Thirteen cytokine/cytokine receptor polymorphisms were genotyped in 170 children after LTx, and related to: EBV DNAemia, CHVL onset and the length of CHVL carriage. RESULTS: The study revealed: the protective effect of rare homozygous and heterozygous IL-1ß-511 and IL-1 receptor antagonist (IL-1RN VNTR) genotypes against viremia within the first year after LTx (OR=0.28, p=0.0007 and OR=0.35, p=0.009, respectively); the protective effect of CC chemokine ligand 2 (CCL2)+1543CT and TT genotypes against CHVL onset (OR=0.38, p=0.042); and the prolonged CHVL-resolution in IL12B 3'untranslated region (3'UTR) AC individuals (p=0.034). CONCLUSIONS: This data suggests that carriage of IL-1ß-511CT/TT and/or IL-1RN VNTR 1.2/2.2 genotype may be beneficial for combating EBV infection. This is the first study reporting the association of CCL2 and IL12B gene polymorphisms with the CHVL carriage in pediatric LTx recipients.

Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years.

BACKGROUND/PURPOSE: The aim of the study was to analyze changing management and survival of children with hepatoblastoma (HBL) treated in one center. MATERIALS AND METHODS: Over the last 20 years, 51 children with HBL were treated. Surgery was performed in 48 children (94.1%), conventional liver resection in 38 (of those, 2 received a rescue liver transplantation [LTx] for relapse), and total hepatectomy and primary LTx in 10 patients. The remaining 3 patients received only palliative treatment. Patient data were analyzed for survival with respect to PRETreatment EXTent of disease (PRETEXT), metastases, histopathology, conventional resection, and LTx. RESULTS: Survival of children with HBL treated with liver resection is 71% and 80% for primary LTx. Favorable prognostic factors for patient survival was tumor histology as epithelial-fetal subtype and mixed epithelial and mesenchymal type, without teratoid features, and good response to chemotherapy (necrosis, fibrosis). Unfavorable prognostic factors were small cells undifferentiated, transitional liver cell tumor, α-fetoprotein level above 1,000,000 IU/mL and below 100 IU/mL at diagnosis, lung metastases, and local recurrence after initial resection. Survival was related to PRETEXT stage. However, among patients with PRETEXT III and IV, LTx resulted in better survival. CONCLUSION: Liver transplantation is a good option for children with advanced HBL. Early referral of children with potentially unresectable tumors to centers where combined treatment (chemotherapy, surgery including LTx) is available is crucial.

Epstein-Barr virus gene expression and latent membrane protein 1 gene polymorphism in pediatric liver transplant recipients.

Immunosuppressed pediatric transplant recipients are at risk of developing Epstein-Barr virus (EBV)-associated complications (such as post-transplant lymphoproliferative disorders). Monitoring of the EBV DNA level in blood alone has a low predictive value for the post-transplant course of EBV infection and its complications. Therefore, additional prognostic markers are widely sought. The study aim was to analyze EBV gene expression patterns and LMP1 polymorphism in relation to EBV DNA levels in pediatric liver transplant recipients. EBV load measurement, LMP1 variant, and gene expression analysis were performed in collected prospectively multiple blood samples from 30 patients. Several distinct patterns of EBV gene expression were identified: latency 2 (71%), latency 3 (13%), latency 0 (11%), and lytic infection (5%). In most children's multiple blood samples, both EBV gene expression patterns and expression levels of individual EBV genes varied significantly over time. EBV gene expression patterns were not associated with the EBV load. However, the viral load correlated with the LMP1 and LMP2 expression (r = 0.34; P = 0.006, and r = 0.45; P = 0.001, respectively). Two variants of the LMP1 gene were detected, and they were consistent over time in individual patients. A wild type of LMP1 was associated with higher EBV-DNA loads (P = 0.03). This indicates that EBV infection in immunosuppressed patients is a very dynamic process, but changes in the state of EBV infection do not influence significantly the viral load. The latter, however, can be associated with the activity of LMP1 and LMP2 genes, as well as polymorphism of LMP1.

Liver transplantation with ABO incompatible graft under immunoadsorption protocol--case report.

BACKGROUND: ABO incompatible liver transplantation is still controversial, but accepted in selected cases. Recently several authors reported use of the new technology aimed at elimination anti-donor ABO specific hemagglutinins to assist immunosuppression in preventing acute rejection after transplantation. CASE REPORT: We report two cases of liver transplantation in children with ABO incompatible graft under immunoadsorption protocol. Both patients were transplanted urgently (one due to acute decompensation of chronic liver failure and second due to acute liver failure) with ABO incompatible liver grafts. Both patients were in very poor general condition with deterioration of neurological status and there were no suitable ABO compatible grafts at the time. In both cases immunosuppressive protocol consisted of induction with basiliximab, followed by tacrolimus, mycophenolate mofetil and corticosteroids. Additionally in both patients 3 immunoadsorption sessions with Glycosorb ABO® system (Glycorex AB, Sweden), were performed. There were no any acute rejection episodes till now. The only problem observed after transplantation was mild anemia due to low grade hemolysis in the postoperative period. Both patients are alive and well with very good liver function 20 and 26 months after transplantation. CONCLUSIONS: Immunoadsorption therapy can be safely and effectively introduced in recipients of ABO incompatible donor liver.

Long-term monitoring of Epstein-Barr virus DNA load and humoral parameter abnormalities in pediatric liver transplant recipients before development of malignancy.

EBV loads and abnormalities of humoral responses were monitored in 51 pediatric liver transplant recipients as a proposed non-invasive laboratory tool for early detection of changes preceding severe clinical complications. EBV DNA load, concentrations of IgM, IgG, IgA, and monoclonal proteins were determined in each blood sample. EBV DNA was detected in 70.6% of the children, dysgammaglobulinemia of one or more Ig isotype was present in 41.2% of them. MG detected in 43.1% of patients correlated with the presence of EBV DNA (p = 0.003) and was usually preceded by hypergammaglobulinemia. The median maximum EBV load was significantly higher in EBV DNA+/MG+ patients than in EBV DNA+/MG- patients (p = 0.04), although there was no correlation between current viral load and appearance of MG. Four of 15 EBV DNA-negative patients developed MG, preceded by hypergammaglobulinemia in two. Minimization or cessation of immunosuppression in 42 patients, in whom abnormal biomarkers and/or clinical symptoms raised suspicion of disease progression, permitted complete resolution of abnormalities in all but one patient who developed B-NHL and died. Simultaneous monitoring of protein profiles and EBV DNA load together with thorough physical evaluation of children after LTx is important for early implementation of suitable preemptive therapy.

Hemodynamic failure as an indication to urgent liver transplantation in infants with giant hepatic hemangiomas or vascular malformations--report of four cases.

The aim of this study was to present acute hemodynamic failure as a rare indication for liver transplantation in neonates and infants with liver hemangiomatosis. We report four patients aged one to six months with giant liver hemangiomas, with huge arterio-venous shunting within these malformations. In three, many skin hemangiomas were found. All children developed right ventricular failure. In two, a trial of pharmacological reduction was attempted with corticosteroids and cyclophosphamide. In one patient, the arterio-venous fistulas were embolized without any improvement in hemodynamic status. Two children underwent rescue hepatic artery surgical ligation, which did not prevent heart and then multiorgan failure including liver failure. After unsuccessful conventional therapy, all infants were considered for urgent liver transplantation; in three cases, it was performed with a living-related donor, and in one case with a deceased donor. All patients are alive and well with the follow-up between nine and 37 months after transplantation. Liver transplantation should be considered as a rescue treatment in children with hepatic vascular malformations leading to hemodynamic insufficiency when conventional therapy is unsuccessful and multiorgan failure develops.

Liver transplantation for fulminant Wilson's disease in children.

BACKGROUND: Fulminant Wilson's disease (FWD) is rare and fatal condition in children unless liver transplantation is performed, however introduction of new technologies could change this poor prognosis. The aim of our study was retrospective analysis of clinical course, treatment and outcome of children with FWD treated in our institution. MATERIAL/METHODS: Between 1999-2007 we've treated in our hospital 13 patients with mean age of 15.5 yrs with FWD. We performed retrospective analysis of clinical course, biochemical parameters, MELD/PELD score, Wilson score and Kings'-College criteria for LTx in acute liver failure in all these patients. Type of treatment and final outcome were analyzed, as well as qualification for transplantation was reevaluated in each case in accordance to pathological examination of explanted during transplantation livers. RESULTS: The initial symptoms of FWD were typically weakness, abdominal pain and developing later after 5-60 days (mean 20 days), jaundice. Eleven patients developed neurological symptoms with coma lasting for 2-11 days before transplantation or death. Maximal serum bilirubin concentration ranged between 4.5-71.6 mg% (mean 42.24 mg%), INR 2.9-10.0 (mean 5.4). MELD/PELD score was between 21-58 (mean 38), 10 patients fulfilled general King's-College criteria for transplantation in acute liver failure. Wilson's index ranged between 11 and 17 points (mean 13 points). In 11 children urgent liver transplantation (LTx) was performed, 1 child recovered on albumin dialysis and chelating treatment, 1 child died shortly after very late referral to our center. Actual follow-up of living patients is 0.36-7.43 years (mean 2.57 yrs), all are doing well with good liver function. CONCLUSIONS: FWD lead to death in almost all pediatric patients if LTx can not be performed, however early introduction of albumin dialysis (MARS) and chelating therapy allowed for survival without transplantation in single patient. It seems also that MARS therapy allows for at least prolongation of waiting time for LTx. Wilson's was slightly better predictor of need for LTx in our patients than classical King's-College criteria.

Aspergillosis in children after liver transplantation: Single center experience.

Aspergillus infection in immunocompromised patients is associated with high morbidity and mortality. We retrospectively reviewed cases of Aspergillosis (A), in a series of 277 children who received LTx between 1990 and 2006. All children were given antifungal prophylaxis after transplantation. Aspergillosis was identified in 10 cases (3.6%) and diagnosis was confirmed when clinical symptoms were associated with identification of Aspergillus sp. or detection of galactomannan antigen. Incidence of Aspergillosis considerably decreased from 6.9% to 0.6% when liposomal amphotericin B was introduced as prophylaxis in high-risk patients. Mean time since LTx to Aspergillosis was 14.5 days. Histologically, Aspergillosis was diagnosed in two cases. Galactomannan antigen was present in two recipients. Aspergillus infection occurs usually within first 30 days after transplantation as a result of a combination of several risk factors. Following risk factors were observed: multiple antibiotic therapy, prolonged intensive care unit stay, poor graft function, retransplantation, relaparotomies, co-infection. Amphotericin B was administered in all cases. Two patients (20%) died because of Aspergillosis Liposomal Amphotericin B prophylaxis in high-risk children decreases the incidence of Aspergillus infection. High index of suspicion and early diagnosis followed by intensive treatment with amphotericin B facilitates achieving mortality rate lower than presented in other reports.

[Living related liver transplantation - analysis of the first 102 cases]. / Transplantacja watroby od zywych dawców rodzinnych - analiza pierwszych 102 przypadków.

THE AIM: of the study was to analyse the first 102 living-related liver transplantations performed in Poland at the Children's Memorial Health Institute. MATERIAL: between November 1999 and January 2007 102 living-related liver transplantations were carried out in 101 patients. In 63 the patients the indication for liver transplantation was biliary atresia, in 7 - intrahepatic cholestasis, in 11 - acute liver failure, in 9 - hepatic tumour, in two - graft insufficiency. The remaining indications included hepatic cirrosis in course of cystic fibrosis, Caroli disease and biliary cysts. There were 61 girls and 40 boys aged from 4 months to 11 years (mean 2.5 years). The body weight ranged from 4.5 to 31 kg (mean 12 kg). RESULTS: eighty seven children are alive (86%). Five died in the early posttranplant period (between 2 and 11 days after operation), 9 died in the later period (from 36 days to 5 years and 10 months after the operation). The most serious, life threatening early and late complications were bacterial infections. The most frequent scheme of immunosuppressive treatment was tacrolimus and corticosteroids (64%) and tacrolimus and mycophenolate mofetil (16%). CONCLUSION: living-related liver transplantation is an effective method of treatment of acute and end-stage liver diseases in children with low body mass.

Reversal of tacrolimus-related hypertrophic cardiomyopathy after conversion to rapamycin in a pediatric liver transplant recipient.

Tacrolimus (Tac)-related hypertrophic cardiomyopathy (HCM) has been reported to be an unusual but serious complication affecting pediatric patients after solid organ transplantation. Herein, we present a case of young liver transplant recipient with Tac-induced HCM, treated by discontinuation of Tac followed by conversion to rapamycin (Rap). Our case report points out the potential but rather low risk of HCM during Tac immunosuppression in pediatric liver transplants and demonstrates that replacement of calcineurin inhibitors with mammalian target of Rap (mTOR) inhibitors may be an efficacious therapeutic tool to effect regression of established cardiac hypertrophy.

Bone mineral metabolism in children with biliary atresia after living related liver transplantation. Evaluation of selected parameters.

BACKGROUND: Aim of the study was to analyze the effect of living related liver transplantation on selected parameters of bone formation and resorption in children with liver cirrhosis caused by biliary atresia. MATERIAL/METHODS: 20 children (13F/7M) with biliary atresia aged from 6 month to 2.4 years were enrolled into the study 4-9 days before liver transplantation. Osteocalcin, procollagen 1 aminoterminal propeptide, collagen type 1 crosslinked C-telopeptide, parathyroid hormone and metabolites of vitamin D: 25(OH)D3, 1,25(OH)2D3 were measured before, 3, 6 and 12 months after liver transplantation. RESULTS: Three months after living related liver transplantation statistically significant increase of osteocalcin, collagen type 1 crosslinked C-telopeptide, parathyroid hormone and 1,25(OH)2D3 levels were found. We didn't observe further increase of these parameters during the next 9 months after liver transplantation. There was no difference in 25(OH)D3 levels in patients before and after liver transplantation. CONCLUSIONS: In children after successful living related liver transplantation we observed improvement of selected parameters of bone formation and resorption which indicate stimulation of growing processes and mechanisms of bone geometry modelling.

[Preliminary results and complications of HCV treatment after liver transplantation]. / Wstepne wyniki i ocena powiklan leczenia zakazenia wirusem zapalenia watroby typu C (HCV) u pacjentów po transplantacji watroby.

UNLABELLED: The aim of study was to report the preliminary results and complications of HCV infection treatment after liver transplantation. MATERIAL: Six patients after liver transplantation (one after combine liver and kidney) had been qualified to treatment with pegylated interferon and ribavirin. RESULTS: In four patients the therapy was discontinued due to severe side effects (anaemia, cholestasis, sepsis, acute rejection). In two patients the normalization of biochemical parameters of liver function was achived after treatment. CONCLUSION: HCV treatement in solid organ recipients should be individualised.