Search

Introduction: Transaldolase deficiency (TALDO; OMIM 606003) is a rare inborn autosomal recessive error of the pentose phosphate pathway that, to date, has been diagnosed in 33 patients. Tżhere are few reports regarding the long-term follow-up of these patients.The aim of our study is to present the disease progression in the form of a systematic long-term follow-up of four Polish patients with TALDO., Methods and Results: We report four patients who manifested early onset TALDO. They were monitored with systematic clinical and laboratory examinations for 4-13 years. The dominant feature was an early liver injury, with subsequent renal tubulopathy. All patients presented with osteopenia and poor physical development. Our data shows that polyol concentrations seem to decrease with age., Conclusions: In our patients, a progressive coagulopathy was the most sensitive parameter of liver dysfunction. Nodular fibrosis of the liver developed over the natural course of TALDO. This is the first report of long-term systematic clinical and biochemical monitoring of the disease progress in patients with TALDO.

Cortisol deficiency constitutes a rare cause of neonatal cholestasis. The aim of this manuscript was to present the pathogenesis of cortisol deficiency in neonatal cholestasis. The authors also present the characteristics of selected disorders resulting in cortisol deficiency.

BACKGROUND The diagnosis of post-liver transplant biliary strictures (BS) requires a high degree of clinical suspicion because of the diversity of symptoms and usually mild clinical presentation. If quickly treated, successful outcome is achieved most cases. The aim of our study was to analyze the value of diagnostic methods in BS after pediatric LTx. MATERIAL AND METHODS We retrospectively reviewed clinical data of children with BS after liver transplantation, with the main focus on diagnostic methods, including imaging studies and histology. All patients underwent endoscopic, transhepatic, or surgical treatment of the stricture. RESULTS Sixty-seven patients after LTx performed at the median age of 9.1 years (0.4-18) developed BS, mostly within the first 12 months (40%). Laboratory findings at diagnosis were: bilirubin 4.65 (5.8±SD), GGTP 434 (382.9±SD), and ALT 126.5 (116.8±SD); 16 patients presented with bilirubin level <1 mg% and 4 with GGTP below 100 IU. Ultrasound scan (USS) visualized dilatation of the bile ducts in 53 (79%) patients. Overall sensitivity of hepatobiliary scintigraphy (HBS) was 93%, with dilatation of bile ducts in 69% and impaired excretion in 68% of patients. MRCP showed 100% accuracy in detecting biliary dilatation and a stricture was visualized in 39%. Liver histology was consistent with biliary obstruction in 66%. Treatment of BS was successful in the majority of cases, with 89% graft survival. CONCLUSIONS Non-invasive investigations are highly sensitive in post-transplant BS and should play the key role in diagnostic algorithms.

Purpose: In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx)., Method: We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results., Results: At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85 th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95 th and >85 Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a)., Conclusion: Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.

Objectives: The concentration of bile acids is highly increased in progressive familial intrahepatic cholestasis (PFIC). Bile acids are the end products of cholesterol metabolism, and aid in the absorption of fat-soluble vitamins and dietary fat. The aim of our study was to investigate lipid metabolism in patients with PFIC with focus on the effect of partial external biliary diversion (PEBD)., Methods: In 26 patients with PFIC, who underwent PEBD surgery at the median age of 2.2 years (range: 0.4-16.6), we analyzed the concentrations of lipids and apolipoproteins both before and 6 months after PEBD. Patients were split into 2 groups according to the outcome of surgery (either "good" or "poor"), and were analyzed separately. A "good" result following surgery was defined as complete relief from pruritus, and normalization of total bilirubin (<1.0 mg/dL) and bile acid concentration in serum (<12 μmol/L)., Results: We found abnormal lipid concentrations at baseline in all 26 patients: cholesterol was increased (>190 mg/dL) in 13 patients, phospholipids were increased (>250 mg/dL) in 5 patients, and triglyceride concentration was increased (>150 mg/dL) in 13 patients. After PEBD, the concentrations of plasma cholesterol, triglycerides, and phospholipids decreased significantly, whereas, ApoA-I and high-density lipoprotein cholesterol concentrations increased and the concentrations of apolipoprotein B, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol significantly decreased. PEBD had neither an effect on ApoE concentration nor on lecithin-cholesterol acyl transferase activity. In the group with a "poor" outcome report following PEBD, total serum cholesterol concentration decreased significantly, and no effect on the concentrations of triglycerides and phospholipids were observed., Conclusions: Patients with PFIC present with a high risk of lipid disturbances. PEBD has a beneficial effect on lipid profile in the majority of cases.

Alagille syndrome (AGS) is often associated with symptoms of maldigestion, such as steatorrhea, hypotrophy and growth retardation. Exocrine pancreatic insufficiency was proposed as the underlying cause. We aimed to assess the exocrine pancreatic function with the use of different methods in AGS patients. Concentrations of fecal elastase-1 (FE1) and fecal lipase (FL) activities were measured in 33 children with AGS. The C-mixed triglyceride breath test (MTBT) in a subgroup comprising 15 patients. In all patients studied, FE1 concentrations and FL activities were normal. Abnormal MTBT results were documented in 4 (26.7%) patients. The FE1 and FL levels in MTBT-positive and MTBT-negative children did not differ. The results of this research do not confirm the presence of exocrine pancreatic dysfunction in AGS patients. Routine screening for exocrine pancreatic insufficiency of this group of patients is not necessary.

Progressive familial intrahepatic cholestasis type 2 (PFIC 2) results from mutations in ABCB11 gene coding bile salt export pump (BSEP). Medical treatment is usually unsuccessful and surgery intervention is necessary. Partial external biliary diversion (PEBD) is regarded as the first choice of surgical treatment. Ileal exclusion (IE) is an alternative operation if external stoma is not tolerated; however, a favorable outcome is uncertain. In chronic liver diseases pregnancy brings additional risk of deterioration of liver function and generally is not recommended. We present the first case report of successful pregnancy in a genetically confirmed PFIC 2 patient after surgical conversion from PEBD to IE.

Background: The aim of our study was to retrospectively assess any correlation between graft fibrosis and selected immunological factors in pediatric liver transplant recipients., Material and Methods: The study was performed on 33 patients after living related donor transplantation, divided into 2 groups depending on history of acute rejection episodes after transplantation. We assessed liver biopsies for presence of fibrosis, signs of antibody-mediated rejection, inflammatory infiltrations, and changes in bile ducts. We correlated these findings with assessment of anti-HLA antibodies., Results: Among 14 patients with ACR, a history fibrosis was found in 8 patients (57%). In 19 patients without a history of ACR, fibrosis was found in 9 patients (47%). Anti-HLA antibodies were found in 47% of patients with fibrosis and in only 18.75% of patients without fibrosis. Among 3 patients with signs of antibody-mediated rejection, all had fibrosis in the graft 2 years after transplantation. We did not find any patient with chronic rejection or ductopenia., Conclusions: We suggest that there is a correlation between ACR and development of graft fibrosis present in liver grafts from recipients with normal liver biochemistry. Anti-HLA antibodies class II seems to be most important in development of fibrosis.

Background: Calcineurin inhibitors (CNI) may increase the risk of cardiovascular (CV) events. This prospective study aimed to determine cardiovascular risk factors in pediatric patients after living related liver transplantation (LRLTx) 12 months after the conversion from cyclosporine (CS) to tacrolimus (TAC)., Material/methods: The study group consisted of 7 children (5 females and 2 males) after LRLTx performed at the median age of 3 years (range 0.8-7.2), who received CS monotherapy for at least 5 years before it was switched to TAC. The median age at conversion was years 13.1 years (range 10.1-18). Weight BMI Z-score, 24-h ABPM (ambulatory blood pressure monitoring), renal function assessment, and fasting lipid and oxidative stress profiles were performed before and 12 months after conversion., Results: Within 1-year follow-up, TAC was well tolerated and we did not observe any drug-related adverse effects or severe infections. Renal function, blood pressure, and lipid parameters did not differ after the conversion. Before the conversion, there was lower median glutathione (GSH) levels (748 vs. 776 [µmol/l]) and glutathione peroxidase (GPx) activity (31.4 vs. 32.4 [U/gHb]), but statistical significance was not reached (p>0.05). Asymmetric dimethylarginine (ADMA) levels were higher before conversion to TAC (0.93 vs. 0.69 [µmol/l], p=0.01), as were oxidized LDL (oxyLDL) levels (317 vs. 264 [mU/ml], p=0.04)., Conclusions: There was no significant difference between CS and TAC in risk factors for CV events. Potential benefits in oxidative stress profile resulting from CS to TAC conversion may add another important area for further research.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5-year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice., (© 2013 The Japan Society of Hepatology.)

This study reports clinical, biochemical and histopathological findings associated with a novel homozygous MPV17 mutation in four patients with mitochondrial depletion syndrome. The severe course of the disease, which started in the first weeks of life, was dominated by a failure to thrive, hypotonia and liver dysfunction, with relatively mild neurological involvement. All affected infants died by 1 year of age. Laboratory findings included progressive liver failure (hypertransaminasaemia, icterus, and coagulopathy), recurrent hypoglycaemia, lactic acidaemia, hyperferritinaemia, and increased transferrin saturation. Histological and ultrastructural analyses uncovered significant lipid accumulation in hepatocytes and myocytes. A severe decrease in the mitochondrial/nuclear DNA (mtDNA/nDNA) ratio was found post-mortem in the livers (and in one muscle specimen) of both examined patients. Oxidative phosphorylation system (OXPHOS) Western blotting revealed low levels of complexes I, III and IV subunits. The highlights of our findings are as follows: (i) The novel p.Pro64Arg mutation is the second recurrent MPV17 mutation reported. The phenotype associated with the p.Pro64Arg mutation differs from the phenotype of the relatively common p.Arg50Gln mutation, suggesting the existence of a genotype-phenotype correlation. (ii) Tissues collected from patients during autopsy may be useful for both mtDNA/nDNA ratio assessment and OXPHOS Western blotting., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Antibody-mediated rejection (AMR), associated with the presence of C4d deposits, is well-defined in kidney transplantation but much less documented in liver transplantation (LTx). The aim of our study was to retrospectively analyze a group of pediatric liver transplant recipients who experienced episodes of acute rejection in the past, for the signs of AMR and its impact on liver histology., Material/methods: Our study population consisted of 18 patients after living related donor liver transplantation with a history of acute cellular rejection (1-5/patient). In all of them, actual liver function was good at almost 2-year median follow-up after transplantation. We reassessed all liver biopsies taken from these children between 5 days to 5.7 years after transplantation for signs of acute cellular rejection and antibody-mediated rejection. In all patients, anti-HLA antibodies were also assessed at least 2 years after transplantation (2.18-12.27 years, median 6.795 years)., Results: There were 27 episodes of acute rejection proved by liver biopsy. Signs of AMR were found in 6 of 18 patients (33.3%). In 5 of these patients, donor-specific (DSA) and non-specific anti-HLA antibodies were also identified. In the group of 12 patients with acute rejection without histochemical signs of AMR, anti-HLA antibodies were found in sera of only 5 of 12 patients after transplantation., Conclusions: Our study shows some correlation between C4d-positive reaction in liver biopsies with acute cellular rejection and presence of anti-HLA antibodies, particularly against HLA class II. We did not find any difference in the late graft function, which could be correlated with the presence of AMR. Further studies on larger groups of patients are necessary.

Background & Aims: To date, no studies concerning the presence of small intestinal bacterial overgrowth in patients with progressive familial intrahepatic cholestasis were published. Based upon characteristic of progressive familial intrahepatic cholestasis one can expect the coexistence of small intestinal bacterial overgrowth. The aim of the study was to assess the incidence of small intestinal bacterial overgrowth in patients with progressive familial intrahepatic cholestasis., Methods: 26 patients aged 8 to 25 years with progressive familial intrahepatic cholestasis were included in the study. Molecular analysis of ABCB11 gene was performed in the vast majority of patients. In all patients Z-score for body weight and height, biochemical tests (bilirubin, bile acid concentration, fecal fat excretion) were assessed. In all patients hydrogen-methane breath test was performed., Results: On the basis of first hydrogen-methane breath test, diagnosis of small intestinal bacterial overgrowth was confirmed in 9 patients (35%), 5 patients (19%) had borderline results. The second breath test was performed in 10 patients: in 3 patients results were still positive and 2 patients had a borderline result. The third breath test was conducted in 2 patients and positive results were still observed. Statistical analysis did not reveal any significant correlations between clinical, biochemical and therapeutic parameters in patients with progressive familial intrahepatic cholestasis and coexistence of small intestinal bacterial overgrowth., Conclusions: Our results suggest that small intestinal bacterial overgrowth is frequent in patients with progressive familial intrahepatic cholestasis. Moreover, it seems that this condition has the tendency to persist or recur, despite the treatment.

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.

Autoimmune diseases due to probable common pathogenesis tend to coexist in some patients. Complex clinical presentation with diverse timing of particular symptoms and sophisticated treatment with numerous side effects, may cause diagnostic difficulties, especially in children. The paper presents diagnostic difficulties and pitfalls in a child with Graves' disease, celiac disease and liver function abnormalities.

Microsporidia are intracellular parasites that cause opportunistic infections in humans of various immunological status. Only a few case reports exist on microsporidial infection in solid organ transplant recipients worldwide. The presented study demonstrates the first case in Poland of Enterocytozoon bieneusi infection in a liver transplant patient. Parasites were diagnosed in stool samples using both modified trichrome staining and PCR.

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., (© 2012 John Wiley & Sons A/S.)

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-1β-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-1β-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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

TMA is a rare complication of tacrolimus. Disruption of endothelial cells, platelet aggregation, and intravascular mechanical fragmentation of red cells are core mechanisms of injury; however, exact pathways of toxicity are not clear. The clinical presentation may vary but TMA is a potentially life-threatening condition usually demanding aggressive treatment. We present the case of TMA in a child after living-related liver transplantation (LRLTx) on tacrolimus-based immunosuppressive regiment successfully converted to sirolimus., (© 2011 John Wiley & Sons A/S.)

Progressive familial intrahepatic cholestasis (PFIC), types 1, 2 and 3, are due to defects in genes involved in bile secretion (FIC1, BSEP, MDR3). PFIC and inborn errors of bile acid synthesis (IEBAS) often present in infancy with cholestasis. The distinctive feature of PFIC 1 and 2 and IEBAS is a normal level of GGT, while IEBAS are suspected in patients with low plasma bile acids concentration. Molecular testing, urinary bile acid analysis (IEBAS), liver biopsy and immuno-staining are used for the diagnosis. Some patients with PFIC can be successfully treated with ursodeoxycholic acid or partial external biliary diversion. IEBAS is treated with cholic acid. Liver transplantation is required for cirrhosis with liver failure. Hepatocarcinoma has been reported in PFIC2., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Amoxicillin/clavulanic acid-induced liver injury is a well recognized complication. Presentation and outcome may vary, which is related to individual liver maturity, genetic predisposition, enzyme heterogeneity, intensity of treatment, and drug interactions. In most cases withdrawing the drug is sufficient treatment; however, cases of progressive liver damage leading to liver transplantation have been reported., Case Report: We present the case of an 8-year-old patient after liver transplantation who developed drug induced liver injury (DILI) after amoxicillin/clavulanic acid treatment for upper respiratory tract infection. Jaundice appeared 2 days after cessation of treatment. Clinical presentation and liver biopsy were consistent with DILI. Because of rapidly increasing bilirubin levels, we used 3 boluses of methylprednisolone and ursodeoxycholic acid. The treatment reversed progression of the cholestasis and full recovery was achieved in 3 months., Conclusions: In most cases of DILI, withdrawing the toxic drug is sufficient treatment, but we must be aware of a possible fatal outcome in case of progressive cholestasis. Corticosteroids may have beneficial effects in these patients.,

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., (Copyright © 2011 Wiley Periodicals, Inc.)

Monitoring of circulating Epstein-Barr virus (EBV) DNA in pediatric transplant patients has been shown to be useful in post-transplant patient management. It still remains unclear which blood sample type is more suitable, and how EBV DNA levels in whole blood (WB) correlate with those in peripheral blood mononuclear cells (PBMCs). The aim of this study was to compare EBV DNA load in WB and PBMCs of pediatric transplant recipients. After liver, kidney, or combined liver-kidney transplantation, 172 matched WB and PBMCs samples were collected from 84 children (130 samples from 42 patients consisted of multiple collections). The EBV DNA level in PBMCs was determined by home-made real-time polymerase chain reaction using TaqMan chemistry. In parallel, the viral load (VL) in WB was measured by a commercial LightCycler EBV Quant Kit. The EBV DNA levels and dynamics of VL changes were assessed and compared between WB and PBMCs. The overall correlation between EBV DNA level in PBMCs and WB was statistically significant and high, r(2) =0.87 (P<0.001). However, the sensitivity of EBV detection was lower in WB (93.9%). Longitudinal analysis of EBV DNA load dynamics in PBMCs and WB indicated that EBV DNA load fluctuations were larger in WB, but the trend of decreases and increases, with minor exceptions, was similar in both sample types. The high correlation of EBV DNA levels, as well as the similar dynamics of EBV DNA changes in both sample types, make WB a good alternative to EBV DNA monitoring in PBMCs of pediatric transplant recipients. However, the subtle increase of the VL may be detected earlier in PBMCs., (© 2011 John Wiley & Sons A/S.)

Background: POLG (polymerase gamma) gene mutations lead to a variety of neurological disorders, including Alpers-Huttenlocher syndrome (AHS). The diagnostic triad of AHS is: resistant epilepsy, liver impairment triggered by sodium valproate (VA), and mitochondrial DNA depletion., Material/methods: A cohort of 28 children with mitochondrial encephalopathy and liver failure was qualified for retrospective study of mitochondrial DNA depletion and POLG mutations., Results: The p.W748S POLG gene mutation was revealed in 2 children, the only ones in the cohort who fulfilled the AHS criteria. Depletion of mtDNA (16% of control value) was confirmed post mortem in available liver tissue and was not detected in the muscle. The disease started with drug-resistant seizures, failure to thrive and developmental regression at the ages of 7 and 18 months, respectively. Irreversible liver failure developed after VA administration. Co-existence of epilepsy, VA liver toxicity, lactic acidemia and muscle respiratory chain dysfunction led finally to the diagnosis of mitochondrial disorder (and AHS suspicion)., Conclusions: Our results confirm, for the first time, the occurrence of a pathology caused by POLG gene mutation(s) in the Polish population. POLG mutation screening and mtDNA depletion assessment should be included in differential diagnosis of drug-resistant epilepsy associated with a hepatopathy.

Chronic graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). After the skin, the liver is the second, most frequent target of GVHD, which presenting with hyperbilirubinemia, elevated liver enzymes, and coagulopathy. Progressive destruction of small intrahepatic bile ducts causes vanishing bile duct syndrome and leads to end-stage liver disease. We report 2 successful cases of orthotopic liver transplantation performed in children with severe GVHD after hematopoietic stem cell transplantation from a matched unrelated donor (HSCT-MUD)., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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.

Background: : Depletion of beta-carotene (b-c) has not been extensively studied in children with chronic cholestatic liver disease., Patients and Methods: : We assessed b-c serum concentration in 53 children with cholestatic liver disease: 19 patients operated on for biliary atresia, 12 with Alagille syndrome, and 22 with progressive familial intrahepatic cholestasis. To test b-c absorption, 6 children with chronic cholestasis received a load of 10 mg b-c/kg body weight., Results: : We found decreased b-c concentrations in 45 patients. The absorption of b-c was not detectable in 5 of 6 children studied., Conclusions: : b-c depletion is a common problem of chronic cholestatic liver disease in childhood that can be attributed to disturbed intestinal absorption.

Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations., Methods: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated., Results: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation., Conclusions: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease., (Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Growth retardation is one of the most prominent consequences of childhood cholestatic liver diseases. The pathogenesis of malnutrition is multifactorial and includes reduced calorie intake, fat malabsorption, abnormal protein metabolism, and increased energy expenditure. Poor growth is a typical feature of biliary atresia, cystic fibrosis, progressive familial intrahepatic cholestasis and Alagille syndrome. In some of these features it is not only directly related to impaired nutrient absorption. Liver transplantation is required if liver disease progresses to liver failure - improved nutritional status is achieved within weeks after surgery. Still, patients with Alagille syndrome present with only slight catch-up growth after transplantation, while patients with PFIC and biliary atresia grow significantly.,

Introduction: High prevalence of elevated serum pancreatic enzymes in children with cholestasis with normal fecal elastase-1 concentrations has been documented. However, this state is related predominantly to biliary atresia. Therefore, we aimed to assess pancreatic damage by measuring serum pancreatic enzymes in patients with progressive familial intrahepatic cholestasis type 2 (PFIC type 2)., Materials and Methods: Twenty PFIC type 2 patients with normal serum bilirubin and bile acid concentrations were included in the study. Thirty pancreatic insufficient cystic fibrosis (PI-CF) patients, thirty patients with acute pancreatitis (AP) and thirty healthy subjects (HS) served for the purpose of comparison. In all subjects, serum lipase and elastase-1 levels were measured., Results: In all but one PFIC type 2 patients and all HS normal lipase activities were found. Serum elastase-1 concentrations were normal in all PFIC type 2 patients and HS. The enzyme levels were very similar in both groups studied. Lipase activities in PFIC type 2 patients were significantly higher than in PI-CF patients (p < 0.00001) and lower than in patients with AP (p < 0.00001). Serum elastase-1 levels in PFIC type 2 patients were significantly lower than in patients with AP (p < 0.00001) and not different from those in PI-CF patients. In conclusion. serum pancreatic enzymes in patients with PFIC type 2 are normal. No pancreatic damage in these patients could be detected.

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.

Background & Aims: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy., Methods: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome., Results: Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 [confidence limits, 1.7-8.1; P = .003])., Conclusions: With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.

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.

Alpha1-antitrypsin deficiency (alpha1-ATD) is a genetic disorder that may predispose to chronic liver disease. The clinical manifestations and prognosis of this disorder are variable. The aim of the study was to evaluate the clinical presentation and liver tests in two groups of children with alpha1-ATD: those with a good prognosis who survived long term with their native liver, and those with a bad one, requiring liver transplantation (OLT) or dying before OLT. We studied 59 children homozygous for alpha1-ATD admitted to our hospital with cholestasis or chronic hepatitis since infancy. Patients without liver transplantation were regarded to be the good prognosis group I (n=45). In contrast the 11 children who required liver transplantation and the three who died before OLT were the bad prognosis cohort (Group II, n=14). We analyzed the laboratory parameters of cholestasis, hepatitis, and liver insufficiency in both groups. In the group with a good prognosis, eight children still suffered from cholestasis at the ages of 9 to 14 years while nine had hepatitis at the ages of 9 to 14 years. We observed a temporarily increased international normalized ratio (1.2 to 1.5) in eight subjects at the ages of 1 month to 17 years, and slight hypoalbuminemia (30 to 35 mg/dL) in nine children at the ages of 1 month to 10 years. OLT was performed in 11 children at the ages of 10 to 17 years. Our center's experience suggested that in the PiZZ patients with portal hypertension, esophageal varices, or deterioration of hepatic function, liver transplantation should not be delayed.

Immunosuppressive and antibacterial regimens in children after liver transplantation create a gut microflora imbalance that can be indirectly measured by the activity of fecal enzymes. The aim of this study was to specify the influence of diet supplementation with probiotic Lactobacillus casei DN on the activity of beta-glucuronidase, beta-glucosidase, and urease. Twenty-five children after liver transplantation (13 girls, 12 boys) ages 3 to 17 years were enrolled in the study. Two months after bacteria application the levels of all 3 enzymes decreased, reaching statistical significance for beta-glucuronidase and beta-glucosidase. Complete rebound in enzyme activity was observed months after the end of probiotic supplementation. We concluded that Lactobacillus casei DN-114001 consumption decreased fecal enzyme activity, a beneficial effect limited to the period of bacteria intake.

Nonalcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to highlight NASH as a rare but possible problem in children. We present a case of 13-yr-boy with a well-established diagnosis of liver cirrhosis secondary to NASH, who underwent orthotopic liver transplantation (OLT) at the age of 13 years. Six months after transplantation recurrence of NASH in the graft was diagnosed. In the treatment metformin was used with good effect.

Organ transplantation is a risk factor for atherogenesis that may be related to immunosuppressive therapy. Increased free radical generation may even aggravate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors for atherogenesis as well as carbohydrate metabolism and antioxidant status among children after liver transplantation. We studied 35 children at 3 to 5 years after liver transplant in whom the following parameters were assessed: total cholesterol; triglyceride; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol; apolipoproteins B, AI, E, lipoprotein (a); vitamin E; glutathione; glucose; insulin; and glutathione peroxidase activity. Three subgroups of patients were assessed according to the immunosuppressive therapy: cyclosporine (CsA), tacrolimus (Tac), or mycophenolate mofetil (MMF) in combination with low-dose CsA or Tac. We observed differences among the subgroups only in total cholesterol (CsA: 131.6 to 285.6; Tac: 144.0 to 181.61; MMF: 132.1 to 181.2) and LDL-C (CsA: 79.4 to 126.9; Tac: 42.2 to 118.8; MMF: 74.2 to 117.3). Lipid metabolism was not significantly disturbed among children after liver transplantation, an observation that does not point to a high risk of atherogenesis. CsA seems to have the strongest untoward effect on cholesterol metabolism. Decreased GSH concentration after liver transplantation may be related to slightly impaired liver function, but GPx activity and vitamin E concentrations remained normal.

Transmission of hepatitis B virus (HBV) infection from donors negative for hepatitis B surface antigen (HBsAg) but positive for antibody to hepatitis B core antigen (anti-HBc) have been reported. The aim of our study was to evaluate the outcomes of recipients who received liver grafts from living related donors with serological evidence of previous exposure to hepatitis B virus (HBsAg-negative/anti-HBc-positive) after recipient vaccination against HBV before and after liver transplantation.

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.

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.

Objective: Infants with chronic cholestasis may require parenteral nutrition with lipid emulsions to provide energy and essential fatty acids but the optimal strategy is controversial., Methods: We studied the effects of parenteral lipid emulsions with long-chain triacylglycerols (LCTs) or a mixture of LCTs and medium-chain triacylglycerols (MCTs/LCTs) on serum bilirubin and lipid metabolism in cholestatic infants who received these 20% emulsions in alternating order for 3 d each, together with a glucose and amino acid infusion., Results: Of 11 recruited infants, two dropped out because enteral feeding could be established. In nine infants (2-8 mo of age, mean age 4.2 mo) who completed the study, serum bilirubin decreased from baseline to 6 h after the end of LCT infusion (from 8.5 +/- 2.0 to 7.8 +/- 1.8 mg/dL, mean +/- SEM, P < 0.05) and MCT/LCT infusion (7.9 +/- 6.5 to 7.1 +/- 6.5 mg/dL, P < 0.05). Cholesterol, triacylglycerol, and phospholipid concentrations in plasma and in chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein were not changed by either emulsion. Total polyunsaturated fatty acid contents in high-density lipoprotein phospholipids increased during LCT infusion (from 29.8 +/- 0.9 to 35.9 +/- 1.4% wt/wt, P < 0.05) and MCT/LCT infusion (from 30.4 +/- 1.0 to 33.0 +/- 0.7%, P < 0.05). The long-chain polyunsaturated fatty acid docosahexaenoic acid increased only with the LCT infusion. Because docosahexaenoic acid availability during infancy is important for early visual and cognitive development, the use of soybean oil-based lipid emulsions may be preferable for infants with severe progressive cholestasis., Conclusion: The MCT/LCT and LCT emulsions showed a good metabolic tolerance in infants with chronic cholestasis but had a differential effect on high-density lipoprotein phospholipid contents of arachidonic and docosahexaenoic acids.

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.

Objective: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is a rare, autosomal, recessive, inherited disease resulting from mutations in the ATP8B1 gene which is expressed at high levels in the small intestine and pancreas and at lower levels in the liver. Given this expression pattern, patients might be expected to have a pancreatic phenotype. Although pancreatitis and steatorrhea have been reported in patients with PFIC1, the available data on pancreatic function are not fully convincing. Therefore, the objective of this study was to assess exocrine pancreatic function in patients with PFIC1., Material and Methods: Three subjects with a diagnosis of PFIC1 were included in the study. The diagnosis was confirmed by molecular analysis of ATP8B1. Prior to surgical treatment (biliary diversion), two patients had steatorrhea and in the third patient, a borderline value for fecal fat excretion was documented. In one patient, liver transplantation also was subsequently performed. Exocrine pancreatic secretion was assessed by the use of fecal elastase-1 and chymotrypsin tests. Fecal lipase concentrations were determined in order to exclude isolated lipase deficiency. Other typical diagnostic procedures were performed annually., Results: The results of the fecal tests were within the normal range. None of the three patients experienced any episodes that could be related to acute or chronic pancreatitis. Laboratory tests including serum amylase and lipase tests were always normal. Abdominal ultrasonography findings did not show any pancreatic pathology., Conclusions: Pancreatic secretion in the study patients with progressive familial intrahepatic cholestasis type 1 was normal. The observed steatorrhea was not related to pancreatic insufficiency.

Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)--or "neonatal hepatitis" suggesting PFIC--that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11.

Introduction: focal nodular hyperplasia (FNH) is a benign tumour of the liver, often discovered incidentally. It occurs mainly in women between 25-44 years old. Though it is rarefy reported in children the evidence has been growing in the recent years., The Aim: of our work was to show our experience of focal nodular hyperplasia in pediatric cases., Material and Methods: 10 children, aged 6-17 years, were hospitalized in the Children's Memorial Health Institute between 2000 and 2005, with provisional diagnosis of focal nodular hyperplasia. In all children radiological examination was performed. In some cases laparotomy and operative liver biopsy was carried out., Results: only in 3 children diagnosis of FNH was made from radiological examination. 6 children needed laparotomy and operative liver biopsy. Although operative resection of FNH lesions was carried out in some patients, the authors observed recurrence of hepatic lesions., Conclusions: our experiences confirm that nowadays the conservative approach should to be standard procedure in children with FNH. Only in doubtful cases laparotomy is recommended.

In progressive familial intrahepatic cholestasis type 2 (PFIC-2), severe steatorrhea is often documented. However, pancreatic exocrine secretion has not yet been studied. In 14 children with PFIC-2, pancreatic function was assessed using standard fecal tests. Normal fecal lipase concentrations excluded isolated lipase deficiency. No differences in fecal elastase-1 concentrations and chymotrypsin activities were detected between PFIC-2 patients with or without steatorrhea, nor between these patients and healthy subjects. In conclusion, pancreatic exocrine function in patients with PFIC-2 is normal. Steatorrhea observed in those patients is not related to pancreatic insufficiency.

Amanita phalloides poisoning is one of the most dramatic medical invents. The course of the illness may vary from mild to the lethal, with signs of fulminant liver insufficiency with coma and multiorgan failure. When hepatic encephalopathy (III/IV degrees) occurs the prognosis is very poor. In definite cases the liver transplantation is necessary. The authors present severe Amanita phalloides poisoning in three family members, who due to fulminant hepatic failure underwent liver transplantation. The two of them (son and father) transplanted accordingly in fifth and seventh day after poisoning, survived. Mother, in whom transplantation started in ninth day after poisoning, died intraoperativel with signs of massive hemorrhage, and cardiac arrest.