Biomedical subjects

Irena Jankowska

Publications and source records attributed to Irena Jankowska.

9 recordsLinked to original sources

PubMed2006

Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency.

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.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Normal pancreatic secretion in children with progressive familial intrahepatic cholestasis type 1.

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.

Adenosine Triphosphatases↗

PubMed2006

Exocrine pancreatic function in children with progressive familial intrahepatic cholestasis type 2.

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.

Adolescent↗

PubMed2006

[Amanita phalloides poisoning as an indication for liver transplantation in three family members].

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.

Adolescent↗

PubMed2005

[Complications in a patient with liver cirrhosis and HCV coinfection during treatment with peginterferon and ribavirin].

Authors present a case of 15-years old girl with liver cirrhosis due to biliary atresia with HCV coinfection with portal hypertension after several episodes of variceal bleeding treated primarily with sclerotherapy and later with transjugular intrahepatic porto-systemic stent shunt. In a patient during the combined peginterferon alfa-2b and ribavirin treatment a decompensation of liver occurred with necessity for liver transplantation.

Adolescent↗

PubMed2004

Characterization of mutations in ATP8B1 associated with hereditary cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1-3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened.

Adenosine Triphosphatases↗

PubMed2002

Long-chain PUFA supplementation improves PUFA profile in infants with cholestasis.

Long-chain PUFA (LCP) deficiency is a frequent complication in cholestatic infants. We investigated the effects of LCP-supplemented formula on EFA status in infants with cholestasis. Twenty-three infants with cholestasis (biliary atresia after surgery, 8; intrahepatic cholestasis, 15) aged 1.9 to 4.9 mon (median 3.1 mon) were randomized to receive commercial infant formulas either without LCP or with LCP from egg phospholipids for 1 mon. Liver tests, nutrient intakes, and plasma phospholipid FA (%w/w) were determined at baseline and after intervention. At baseline, patients had high serum direct bilirubin levels (5.9 +/- 3.0 mg/dL; mean +/- SD), they were malnourished (body fat mass: 40 +/- 13% of normal) and presented with PUFA deficiency [plasma phospholipid PUFA: 28.43%w/w (26.56-30.53) in patients vs. 37.02%w/w (34.53-39.58) in controls; median (1st-3rd quartile)] with elevated Mead acid and palmitoleic acid. LCP-supplemented (n = 11) and -nonsupplemented groups (n = 12) did not differ in age, indicators of liver function, and EFA status at baseline. After the intervention, LCP-supplemented infants had higher levels of arachidonic acid [7.2 (5.9-8.8) vs. 4.2 (3.0-5.3) %w/w; P < 0.001] and DHA [2.8 (2.2-3.2) vs. 1.6 (1.0-2.1) %w/w; P < 0.05], accompanied by increased TBARS concentration: 1.9 (1.4-2.2) vs. 1.3 (1.1-1.6) nmol/mL; P < 0.05]. We concluded that LCP-supplemented formulae improve LCP status of infants with severe cholestasis but may enhance lipid peroxidation.

Bile Acids and Salts↗

PubMed2002

[Cholestatic liver disease in children].

Cholestatic liver disease constitutes a large part of chronic liver diseases during infancy. It is caused either by extrahepatic disorders (obstruction) or by intrahepatic cholestasis (functional). The differential diagnosis should be done as early as possible because the delayed surgical therapy in extrahepatic cholestasis has a very bad prognosis. Intrahepatic cholestasis may be caused by a broad spectrum of different disorders such as congenital infection, endocrine, chromosomal abnormalities or inborn errors of metabolism. Familial clustering is typical for the Byler's disease, Alagille's syndrome, PFIC, errors of bile acid synthesis or alpha-1-ATD. The established diagnosis allows to start etiological treatment: dietary--in metabolic diseases, antibiotics--in bacterial infections, antiviral--in viral infections etc. To lower bile acids level pharmacological treatment (UDCA) or surgical procedures (hepatoportoenterostomy, partial biliary diversion) should be performed. In progressive cholestasis the only effective therapy is liver transplantation.

Age Factors↗

PubMedDate not supplied

[Focal nodular hyperplasia - own experiences].

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.

Adolescent↗