Risk for Recurrence in Long-Term Follow-Up of Children after Liver Transplantation for Hepatoblastoma or Hepatocellular Carcinoma.

The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation.

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.

The Impact of Hepatic Artery Thrombosis on the Outcome of Pediatric Living Donor Liver Transplantations.

The aim of our study was to assess risk factors for hepatic artery thrombosis (HAT) and to evaluate the impact of HAT management on long-term outcomes after pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 400 patients who underwent primary LDLT between 1999 and 2020. We compared preoperative data, surgical factors, complications, and patient and graft survivals in patients with HAT (HAT Group) and without HAT (non-HAT Group). A total of 27 patients (6.75%) developed HAT. Acute liver failure, a hepatic artery (HA) anastomosis diameter below 2 mm, and intraoperative HA flow dysfunction were significantly more common in the HAT Group (p < 0.05, p = 0.02026, and p = 0.0019, respectively). In the HAT Group, 21 patients (77.8%) underwent urgent surgical revision. The incidence of biliary stenosis and retransplantation was significantly higher in the HAT Group (p = 0.00002 and p < 0.0001, respectively). Patient and graft survivals were significantly worse in the HAT Group (p < 0.05). The close monitoring of HA flow with Doppler ultrasound during the critical period of 2 to 3 weeks after LDLT and the immediate attempt of surgical revascularization may attenuate the elevated risk of biliary stenosis, graft loss, and the need for retransplantation due to HAT.

Choledochal Cyst Excision in Infants-A Retrospective Study.

A choledochal cyst is a rare malformation primarily diagnosed in children. The only effective therapy remains surgical cyst resection followed by Roux-en-Y hepaticojejunostomy. Treating asymptomatic neonates remains a point of discussion. Between 1984 and 2021, we performed choledochal cyst (CC) excision in 256 children at our center. Out of this group, we retrospectively reviewed the medical records of 59 patients who were operated on under one year of age. Follow-up ranged from 0.3 to 18 years (median 3.9 years). The preoperative course was asymptomatic in 22 (38%), while 37 patients (62%) had symptoms before surgery. The late postoperative course was uneventful in 45 patients (76%). In symptomatic patients, 16% had late complications, while in asymptomatic patients, only 4%. Late complications were observed in the laparotomy group in seven patients (17%). We did not observe late complications in the laparoscopy group. Early surgical intervention is not followed by a high risk of complications and may prevent the onset of preoperative complications, giving excellent early and long-term results, especially after minimally invasive laparoscopic surgery.

Impact of Graft Size Matching on the Early Post-Transplant Complications and Patients Survival in Children after Living Donor Liver Transplantations.

We aimed to assess the impact of the graft-recipient weight ratio (GRWR) on early post-transplant complications and patient survival rates in children after living donor liver transplantation (LDLT). We retrospectively analyzed 321 patients who underwent LDLT from 2004 to 2019. The recipients were categorized into four groups: 37 patients had a GRWR ≤ 1.5% (Group A), 196 patients had a GRWR > 1.5% and ≤3.5% (Group B), 73 patients had a GRWR > 3.5% and <5% (Group C) and 15 patients had a GRWR ≥ 5% (Group D). Incidence of early surgical complications including vascular complications, biliary complications, postoperative bleedings, gastrointestinal perforations and graft loss were comparable among groups with a different GRWR. Delayed abdominal wound closure was more common in patients with a GRWR > 3.5%. Recipients with a GRWR < 5% had a significantly better prognosis concerning patients and graft survival. Using grafts with a GRWR < 5% allows us to expand the donor pool and decrease the risk of mortality while on the waiting list, when patients at the time of transplantation have less advanced liver disease. LDLT with a GRWR ≥ 5% is related to a higher risk of poor outcome, and thus should be an option for treating selected patients when the risk of a delayed transplantation is high and access to deceased donors is limited.

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.

A Report of 2 Infant Siblings with Progressive Intrahepatic Familial Cholestasis Type 1 and a Novel Homozygous Mutation in the ATP8B1 Gene Treated with Partial External Biliary Diversion and Liver Transplant.

BACKGROUND Current treatment options for progressive intrahepatic familial cholestasis type 1 (PFIC-1) comprise ursodeoxycholic acid (UDCA), partial external biliary diversion (PEBD), and liver transplantation (LTx). The role and timing of LTx in PFIC-1 remains debated. We present 2 case reports of male siblings with PFIC-1 who benefited from different treatments. CASE REPORT Both siblings harbored a homozygous truncating mutation in ATP8B1 characteristic for PFIC-1 and both underwent PEBD after unsuccessful UDCA treatment at the age of 7 and 5 months, respectively. The older brother, after initial improvement of symptoms, developed severe pruritus, cholestasis, and diarrhea 9 months after PEBD and underwent LTx at the age of 16 months. Chronic diarrhea and abnormal transaminases activity appeared soon after transplantation. A liver biopsy was performed 3 months after LTx and showed severe macrovesicular steatosis (95%). Sixteen months after LTx, total biliary diversion was performed, with rapid relief from diarrhea and significant regression of graft steatosis by <30%. In his brother we observed persistent severe pruritus and cholestasis after PEBD, but we decided to postpone LTx due to lack of a living related donor and risk of graft steatosis. Eight months after PEBD, bilirubin and bile acids significantly decreased and pruritus disappeared completely. Currently, in 5-year follow-up, liver function is stable and he has no pruritus. CONCLUSIONS The good effect of PEBD may be delayed in PFIC-1, even in severe mutation; thus, the decision to perform LTx should be made cautiously. Total biliary diversion is an efficient procedure in case of persistent symptoms after LTx and can reverse graft steatosis in children with PFIC-1.

Health Status in Long-Term Survivors of Hepatoblastoma.

The aim of this study was to evaluate the health status of children cured from hepatoblastoma. Forty-five patients with hepatoblastoma treated between 1996-2014 were assessed. The recorded data included sex, age at diagnosis, disease stage, treatment methods, time since diagnosis, and the evaluation of health status domains which included performance status, growth development, hearing, cardiovascular, skeletal, gastrointestinal, genitourinary, neurological, and hematological function. There were 30 boys and 15 girls. The age at diagnosis ranged from one month to 14 years (median one year). At the time of the health status evaluation, the youngest patient was 5.5 years old and the oldest was 21 years of age (median-10 years). All patients were treated according to the Childhood Liver Tumors Strategy Group-SIOPEL recommendations, though they were not active participants of the studies. The median cumulative dose of cisplatin was 520 mg/m2 and 360 mg/m2 for doxorubicin. Thirty-six patients underwent partial hepatectomy, and nine total hepatectomy and liver transplantation. At a median of nine years from diagnosis, 68% of hepatoblastoma survivors had experienced at least one chronic health condition of any grade. The most frequent late complication was ototoxicity (28.8%), and the most serious were second malignancies (6.6%) and cardiomyopathy (4.4%). Conclusion: Survivors of hepatoblastoma are at risk for long-term complications. They require long-term monitoring for late effects.

Long-term follow-up in children with progressive familial intrahepatic cholestasis type 2 after partial external biliary diversion with focus on histopathological features.

Progressive familial intrahepatic cholestasis (PFIC) comprises a group of rare cholestatic liver disorders of childhood that could lead to liver cirrhosis. Nowadays, the partial biliary diversion procedure is still a therapeutic option in non-cirrhotic children with PFIC1 or PFIC2 after an ineffective ursodeoxycholic acid (UDCA) therapy. However, the relevant disadvantage of the partial external biliary diversion (PEBD) is that adolescent patients could not accept a permanent stoma. In some of them, despite of good clinical and biochemical results of this procedure, the ileal exclusion (IE) procedure had to be performed many years after PEBD. Our aims were to find the most characteristic early microscopic features of the disease as well as to compare changes in the liver biopsy specimens at the time of diagnosis and long-time (more than 10 years) after a surgical procedure. We examined retrospectively 8 liver biopsies from 4 PFIC2 patients comparing the results from the first biopsies done at the time of PFIC diagnosis and the second ones, done many years after PEBD. The characteristic lobular rosette formations of hepatocytes were found in all patients at the time of diagnosis. Cholestasis was observed in each patient, but only in two of them, centrally located bile plugs were found. The majority of hepatocytes showed degenerative changes from mild to severe degree. In the follow-up biopsies, cholestasis completely disappeared in 3 patients and decreased significantly in 1 other patient. Based on Batts and Ludwig fibrosis scoring system, the liver fibrosis had resolved in two out of three patients. The formation of lobular rosettes with centrally located bile plugs and degenerative changes of hepatocytes seem to be the most characteristic microscopic features in early liver biopsies in PFIC2 patients. Partial external biliary diversion significantly improved the clinical, anthropological, biochemical as well histological outcome of the patients.

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.

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.

Ileal exclusion in children with progressive familial intrahepatic cholestasis.

OBJECTIVES: Children with progressive familial intrahepatic cholestasis (PFIC) rarely benefit from medical treatment and most patients require surgical intervention. Partial external biliary diversion (PEBD) is presently the treatment of choice but for those who cannot benefit from PEBD, an alternative surgical procedure--ileal exclusion (IE)--was introduced. The aim of this study was to analyze our experience with IE in children with PFIC. METHODS: This procedure was performed in 9 patients (6 girls, 3 boys) at the median age of 11 years (range 8-21). In 4 children, it was the primary operation (group 1), and in 5, IE was performed after PEBD (group 2). All of the patients were screened for ABCB11 and ATP8B1 mutations, and in 3 cases, PFIC type 2 was confirmed. RESULTS: Median follow-up after IE surgery was 8.5 years (range 3-14). In group 1, 1 patient had to be converted to PEBD and the remaining 3 children experienced alleviation in pruritus and decrease in bilirubin and bile acids concentrations 2 and 5 years after IE. After 10 years, only 2 children were still accessible for follow-up. In both, pruritus varied and elevated serum bile acids were observed. Of the 5 patients who underwent IE after PEBD, 1 eventually required liver transplantation, 1 developed varying degree of pruritus, and 3 female patients, operated on because of aesthetic reasons, had excellent outcomes. CONCLUSIONS: IE is an alternative rescue option to PEBD and should be offered cautiously, only to patients who cannot benefit from PEBD.

Treatment of undifferentiated embryonal sarcoma of the liver in children--single center experience.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) represents less than 5% of all malignant hepatic tumors in childhood. It is considered an aggressive neoplasm with an unfavorable prognosis. The aim of this paper is to present a single center experience in the treatment of children with UESL. MATERIALS AND METHODS: Ten children with UESL were treated between 1981 and 2012. Age at diagnosis ranged from 4 months to 17 years (median age, 6 years and 9 months). Surgery after neoadjuvant chemotherapy (CHT) was performed in 7 patients, and in 3 patients primary surgery was done. Adjuvant chemotherapy was administered in all 10 patients (CYVADIC, CAV, CAV/ETIF/IF+ADM, CDDP/PLADO). Right hemihepatectomy was performed in 1 patient, extended right hemihepatectomy in 6, and partial resection of the right lobe (segments V-VI, segment V) in 2 patients. One patient with unresectable tumor affecting both lobes was listed for liver transplantation (LTx). RESULTS: Follow-up from diagnosis ranged from 50 to 222 months (mean 138 months). Among 9 patients treated with partial liver resection, distant metastases/local recurrence was not observed in any, and disease-free survival in this group is 100% (9 patients alive). The patient that underwent liver transplantation died of multiorgan failure 4 months postoperatively. However, this patient was misdiagnosed as having hepatoblastoma (HBL) and received PLADO chemotherapy. The overall survival rate is 90%. CONCLUSION: Excellent results with long-term survival can be achieved in children with UESL with conventional therapy, including a combination of neoadjuvant and adjuvant chemotherapy and surgery, even in large extensively growing tumors.

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.

Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study.

Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4 correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038). In short-term observation, successful LRLTx led to bone metabolism normalization triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone status coincided with disturbances in bone metabolism. Bone metabolism markers, especially P1NP and CTx, appeared to be good predictors of changes in bone status evaluated by DXA.

Liver transplantation in children with biliary atresia and polysplenia syndrome.

BACKGROUND: Children with biliary atresia and polysplenia syndrome (BA-PS) have always been considered as high risk liver transplant recipients due to technical problems during transplant surgery. We report single-center experience with liver transplantation in children with this syndrome. MATERIAL/METHODS: Between 2000 and 2010, 401 liver transplantations were performed in 358 children, including 6 patients with BA-PS, who underwent living (5 patients) or deceased (1 patient) donor liver transplantation. Patients demonstrated various malformations: absence of retrohepatic vena cava (3), intestinal malrotation (3), preduodenal portal vein (1), hepatic artery anomalies (3), cardiac anomalies (2), and situs inversus (1). Transplantations were performed at the patient age of 8 months to 11 years. RESULTS: There were no serious technical problems during the operations, and we did not have to use vascular conduits for graft revascularization in any case. All patents were alive at follow-up between 14 and 123 months after transplantation (mean 75 months). We observed, however, increased incidence of PV thrombosis and biliary complications in these patients, which did not influence patient and graft survival. In 1 child with graft failure due to chronic rejection after discontinuation of immunosuppression due to PTLD, retransplantation was performed. CONCLUSIONS: Results of liver transplantation in children with BA-PS are as good as for other indications and non-syndromic BA in an experienced pediatric liver transplant center. Although there were no serious technical problems during deceased or living related donor transplantation in these children, close observation for possible vascular complications should be the routine in the postoperative period.

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.

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.

Non-resectable hepatic tumors in children - role of liver transplantation.

BACKGROUND: There is a group of children with primary hepatic tumors which can not be resected by conventional partial liver resection. Total hepatectomy followed by liver transplantation may be the only solution in such cases. Authors reviewed own experience with the liver transplantation for unresectable tumors in children and assessed the possible indications and role of transplantation in these patients. MATERIAL AND METHODS: Liver transplantation was performed in 17 children with unresectable hepatic tumors out of total number of 350 children transplanted. Hepatocarcinoma was present in 8 children, hepatoblastoma in 6 and benign giant hemangioma in 3. There was no other option for the treatment which would lead to the oncological cure of children with malignant tumors. All patients with giant hemangiomas were infants transplanted urgently due to circulatory and then multiorgan failure. RESULTS: Survival within whole group is 75.5% (13 of 17 pts), 3 children died of malignant tumor recurrence, one of other causes. All 3 children with benign tumors are alive and well. Actual follow-up is from 3 months to 7 years. CONCLUSIONS: Liver transplantation should be considered as option in the treatment of all children with unresectable hepatic tumors. With the careful and individual patient selection significant chances for survival can be achieved in this group of patients which would otherwise not survive with the conventional treatment.