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Ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on the stage of liver fibrosis:The first pediatric study

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World Journal of Gastroenterology 2007年第21期13卷 2918-2922页

作者： Maria Elzbieta Sobaniec-Lotowska Joanna Maria Lotowska dariusz marek lebensztejn Department of Clinical Pathomorphology Medical University of BialystokPoland IIIrd Department of Pediatrics Medical University of BialystokPoland

AIM:To investigate the ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on their location in areas of collagen fibroplasia. METHODS:Morphological investigations were conducted on biopsy material obtained from 40 children,aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis. RESULTS:Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells,the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells,i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells. CONCLUSION:We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.

关键词： Pediatric patients, Oval cells Ultrastructural study Chronic hepatitis B Liver biopsy Fibrosis

Matrix-derived serum markers in monitoring liver fibrosis in children with chronic hepatitis B treated with interferon alpha

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World Journal of Gastroenterology 2006年第21期12卷 3338-3343页

作者： dariusz marek lebensztejn Maria Elzbieta Sobaniec-Lotowska Maciej Kaczmarski Michael Voelker Detlef Schuppan Ⅲrd Department of Pediatrics Medical University of Bialystok Poland Department of Clinical Pathomorphology Medical University of Bialystok Poland Bayer Research Krefeld Germany Department of Medicine Ⅰ University of Erlangen-Nuemberg Germanyand Division of Gastroenterology and HepatologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUnited States

To evaluate prospectively 4 selected serum fibrosis markers （tenascin, hyaluronan, collagen Ⅵ, TIMP-1） before, during and 12 mo after IFN treatment of children with chronic hepatitis B. METHODS： Forty-seven consecutive patients with chronic hepatitis B （range 4-16 years, mean 8 years） underwent IFN treatment （3 MU tiw for 20 wk）. Fibrosis stage and inflammation grade were assessed in a blinded fashion before and 12 mo after end of treatment. Serum fibrosis markers were determined using automated ***： IFN treatment improved histological inflammation but did not change fibrosis in the whole group or in subgroups. Only hyaluronan correlated significantly with histological fibrosis（r = 0.3383, P = 0.022）. Basal fibrosis markers did not differ between responders （42.5%） and nonresponders（57.5%）. During IFN treatment only serum tenascin decreased significantly in the whole group and in nonresponders. When pretreatment values were compared to values 12 mo after therapy, TIMP-1 increased in all patients and in nonresponders, and hyaluronan decreased in all patients and in ***： Tenascin reflects hepatic fibrogenesis and inflammation which decreases during IFN treatment of children with chronic hepatitis B. TIMP-1 correlates with nonresponse and hyaluronan with histological fibrosis.

关键词： Biopsy Collagen Ⅵ Fibrogenesis Fibrosis Hepatitis B virus Hyaluronan Serum marker Tenascin TIMP-1

Diagnostic accuracy of serum biochemical fibrosis markers in children with chronic hepatitis B evaluated by receiver operating characteristics analysis

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World Journal of Gastroenterology 2005年第45期11卷 7192-7196页

作者： dariusz marek lebensztejn Elzbieta Skiba Jolanta Tobolczyk Maria Elzbieta Sobaniec-Lotowska Maciej Kaczmarski Ⅲrd Department of Pediatrics Department of Children Allergology Department of Clinical Pathomorphology

METHODS： We determined the serum level of apolipoprotein A-I （APO A-I）, haptoglobin （HPT） and a-2 macroglobulin （A2I） with an automatic nephelometer in 63 children （age range 4-17 years, mean 10 years） with biopsy-verified chronic HBeAg-positive hepatitis B. Fibrosis stage and inflammation grade were assessed in a blinded fashion according to Batts and Ludwig. We defined mild liver fibrosis as a score ≤2 and advanced fibrosis as a score equal to 3. ROC analysis was used to calculate the power of the assays to detect advanced liver fibrosis （AccuROC, Canada）. RESULTS： Serum concentrations of APO A-I, HPT and A2M were not significantly different in patients with chronic hepatitis B compared to controls. However, APO A-I level of 1.19 ng/L had a sensitivity of 85.7% and a specificity of 60.7% （AUC = 0.7117, P = 0.035） to predict advanced fibrosis. All other serum biochemical markers and their combination did not allow a useful prediction. None of these markers was a good predictor of histologic inflammation. CONCLUSION： Apolipoprotein A-I may be a suitable serum marker to predict advanced liver fibrosis in children with chronic hepatitis B.

关键词： Chronic hepatitis B Liver fibrosis Children Apolipoprotein A-I Haptoglobin a-2 macroglobulin

Pediatric non-alcoholic steatohepatitis:The first report on the ultrastructure of hepatocyte mitochondria

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World Journal of Gastroenterology 2014年第15期20卷 4335-4340页

作者： Joanna M Lotowska Maria E Sobaniec-Lotowska Sylwia B Bockowska dariusz M lebensztejn Department of General Pathomorphology Medical University of Bialystok15269 BialystokPoland Department of Medical Pathomorphology Medical University of Bialystok15269 BialystokPoland Department of Laboratory Diagnostics Maria Sklodowska-Curie Memorial Bialystok Oncology Center15027 BialystokPoland Department of Pediatrics Gastroenterology and AllergologyMedical University of Bialystok15274 BialystokPoland

AIM: To investigate the ultrastructure of abnormal hepatocyte mitochondria, including their cellular and hepatic zonal distribution, in bioptates in pediatric non-alcoholic steatohepatitis (NASH).

关键词： Pediatric non-alcoholic steatohepatitis Hepatocyte ultrastructure Megamitochondria with crystalline inclusions Foamy cytoplasm of hepatocytes

Inter-observer variability in histopathological assessment of liver biopsies taken in a pediatric open label therapeutic program for chronic HBV infection treatment

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World Journal of Gastroenterology 2006年第11期12卷 1713-1717页

作者： marek Woynarowski Joanna Cielecka-Kuszyk Andrzej Ka■u■y(n|')ski Aleksandra Omulecka Maria Sobaniec-■otowska Julian Stolarczyk Wojciech Szczepa(n|')ski Department of Gastroenterology Hepatology and Immunology Children's Health Memorial InstituteWarsawPoland Department of Pathology Children's Health Memorial Institute WarsawPoland Department of Pathology Polish Mother Memorial Research Institute ■ód(z|')Poland Department of Pathology Medical University of ■ód(z|') Poland Department of Clinical Pathology Medical University of Bialystok Poland Department of Pathology Medical Academy of Gda(n|')sk Poland Department of Pathology Jagiellonian University Medical College KrakówPoland

AIM： To our knowledge, the inter-observer variability of the liver biopsy findings in HBV-infected children have not been studied as yet. Hence, we aimed to compare different pathologist＇s assessment of grading and staging in liver biopsies obtained from children prior to interferon treatment. METHODS： We collected 920 biopsies from 11 medical centers. The biopsies were independently reviewed by 6 pathologists from academic centers who assessed Batts-Ludwig score for grading and staging. Satisfactory agreement among observers was defined as at least 60% of observers having the same opinion. Satisfactory dispersion between maximal and minimal score for the same biopsy specimen was defined as a maximum 1 point. RESULTS： Satisfactory inter-observer agreement for grading was obtained in 51.6% and for staging in 75.7% of biopsies. Satisfactory dispersion for grading scores was observed in 44.5% and for staging in 72.7% of cases. CONCLUSION： Our study demonstrates that：（1） pathologists differ in their assessment of grading and staging of liver biopsies; （2） inter-observer variability for staging is lower than that for grading; and （3） regardless of the inter-observer variability of assessments, the majority of children with chronic HBV infection have mild to moderate inflammation and mild to moderate fibrosis.

关键词： Grading Staging Type B Hepatitis Children