• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.2
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• pp.177-193
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• 2005

Purpose: To identify genes specifically expressed in biliary atresia, we compared the patterns of gene expression between biliary atresia and neonatal hepatitis syndrome using cDNA microarray analysis. Methods: Liver tissues were taken from livers of 11 patients (7 patients with biliary atresia and four with neonatal hepatitis) with neonatal cholestasis by needle biopsy. Normal control could be obtained from donor liver tissue during living-related liver transplantation. Total RNA was extracted from each samples and reversely transcribed to make cDNA. Then fluorescent cDNA were pooled and hybridized to the clones on the microarray. Fluorescence intensities at the immobilized targets were measured. Utilizing cDNA arrays of 4.7 K human genes, gene expression profiles were analyzed. Results: Among 4,700 microarray clones, 17 cDNA clones were significantly over-expressed in all 11 patients with neonatal cholestasis, while 20 clones were significantly decreased. Genome-wide expression analysis was carried out in livers obtained at the time of diagnosis. We could identify 49 genes, in which there showed differential expression between biliary atresia and neonatal hepatitis syndrome. Conclusion: This study shows the pattern of differentially expressed genes in biliary atresia and neonatal hepatitis syndrome. We believe that this study can contribute to the understanding of pathogenesis of neonatal cholestasis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.5
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• pp.353-375
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• 2022

No systematic review to date has examined histopathological parameters in relation to native liver survival in children who undergo the Kasai operation for biliary atresia (BA). A systematic review and meta-analysis is presented, comparing the frequency of native liver survival in peri-operative severe vs. non-severe liver fibrosis cases, in addition to other reported histopathology parameters. Records were sourced from MEDLINE, Embase, and CENTRAL databases. Studies followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and compared native liver survival frequencies in pediatric patients with evidence of severe vs. non-severe liver fibrosis, bile duct proliferation, cholestasis, lobular inflammation, portal inflammation, and giant cell transformation on peri-operative biopsies. The primary outcome was the frequency of native liver survival. A random effects meta-analysis was used. Twenty-eight observational studies were included, 1,171 pediatric patients with BA of whom 631 survived with their native liver. Lower odds of native liver survival in the severe liver fibrosis vs. non-severe liver fibrosis groups were reported (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.08-0.33; I²=46%). No difference in the odds of native liver survival in the severe bile duct destruction vs. non-severe bile duct destruction groups were reported (OR, 0.17; 95% CI, 0.00-63.63; I²=96%). Lower odds of native liver survival were documented in the severe cholestasis vs. non-severe cholestasis (OR, 0.10; 95% CI, 0.01-0.73; I²=80%) and severe lobular inflammation vs. non-severe lobular inflammation groups (OR, 0.02; 95% CI, 0.00-0.62; I²=69%). There was no difference in the odds of native liver survival in the severe portal inflammation vs. non-severe portal inflammation groups (OR, 0.03; 95% CI, 0.00-3.22; I²=86%) or between the severe giant cell transformation vs. non-severe giant cell transformation groups (OR, 0.15; 95% CI, 0.00-175.21; I²=94%). The meta-analysis loosely suggests that the presence of severe liver fibrosis, cholestasis, and lobular inflammation are associated with lower odds of native liver survival in pediatric patients after Kasai.

• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.17-23
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• 2003

Purpose : Cholestasis is a major complication in prolonged use of TPN, especially in the neonatal period, but there are few long-term reviews examining the clinical course in premature infants. Thus, in this study, we reviewed premature infants with TPN-associated cholestasis(TPNAC) to determine the incidence, clinical courses and possible risk factors. Methods : Retrospective review of 66 premature infants less than 2,000 gm of birth weight and on TPN for more than two weeks was performed. Cholestasis was defined as a serum direct bilirubin level greater than 2.0 mg/dL. The clinical course of cholestasis was described, and perinatal risk factors were evaluated. Results : TPNAC developed in 21 out of 66 infants(31.8%). The onset was $41.7{\pm}17.4days$ after receiving TPN, and the mean duration was $33.6{\pm}23.4days$. The incidence of TPNAC was significantly correlated with birth weight, and gestational age, and duration of TPN. But, possible etiologic factors, such as incidence of perinatal asphyxia or infection, showed no remarkable differences between infants with TPNAC and those without TPNAC(control). The enteral intake in the third postnatal week was significantly smaller in infants with TPNAC than in the control infants(P=0.033). Conclusion : The enteral intake in the third postnatal week was smaller in the infants with TPNAC than in the control infants. Thus, the incidence of TPNAC may be reduced by increasing the amount of oral intake during TPN in high risk infants.

• Advances in pediatric surgery
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• v.3 no.1
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• pp.6-14
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• 1997

To differentiate biliary atresia from intraheaptic cholestasis, Tc-99m DlSIDA hepatobiliary scintigraphies and percutaneous needle biopsies of 60 consecutive infants were evaluated retrospectively. Twenty three patients had biliary atresia and 37 patients intraheaptic cholestasis(neonatal hepatitis 34, TPN induced jaundice 2 and Dubin-Johnson syndrome 1). All sixty patients underwent Tc-99m DlSIDA hepatobiliary scintigraphy with phenobarbital pretreatment. Of 23 patients with biliary atresia, 22 were correctly interpreted showing 96% sensitivity while of 37 patients with intraheaptic cholestasis, only 12 had intestinal excretion of radionuclide showing 32% specificity. Among the forty needle biopsies, 17 of biliary atresia and 23 of intrahepatic cholestasis, 37 were correctly interpreted as either having biliary atresia or intrahepatic cholestasis. The overall diagnostic accuracy was 93%. Of 3 misdiagnosed cases, the histologic findings of two patients with biliary atresia(aged 43 days and 54 days at the first needle biopsy) were essentially the same as those of neonatal hepatitis. Follow-up biopsies, however, showed findings consistent with biliary atresia. The third one(VLBW premie with history of 8 weeks of TPN) showed mild ductal proliferation and portal fibrosis. This was interpreted as suspicious for biliary atresia. Jaundice resolved gradually. In summary, patients who have intestinal excretion of radionuclide on Tc-99m DlSIDA hepatobiliary scintigraphy, biliary atresia can be ruled out. But the patients who do not have intestinal excretion of radionuclide should have further investigation by needle biopsy. Judicious use of Tc-99m DISIDA hepatobiliary scintigraphy and percutaneous needle biopsy can give a diagnostic accuracy of 95% or more in cases of infantile cholestasis.

• BMB Reports
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• v.29 no.2
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• pp.142-145
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• 1996

To investigate the cause of increased plasma catecholamine levels in liver disease, catechol-O-methyltransferase (COMT), which provides a major route of catabolism for circulating catecholamines, was studied under the cholestasis induced by mechanical biliary obstruction in rats. Monoamine oxidase (MAO) activity and the $K_m$ and $V_{max}$ values for both enzymes were also measured. Cytosolic, microsomal, and mitochondrial COMT activities in the cholestatic liver were significantly decreased throughout the experiment. Microsomal, and mitochondrial MAO activity in the cholestatic liver were also significantly decreased. Vmax values of COMT and MAO were lower. Serum COMT and MAO activities were detected after CBD ligation. These results indicate that plasma catecholamine levels are increased in liver disease due to decreased hepatic degradation of catecholamines by decreased activities of COMT and MAO. The decreased activity of these enzymes is caused by decreased biosynthesis and by flowage into the blood from the damaged hepatocyte.

• Journal of Yeungnam Medical Science
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• v.19 no.1
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• pp.68-72
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• 2002

Dubin-Johnson syndrome is a form of benign, familial idiopathic jaundice presenting with chronic intermittent conjugated hyperbilirubinemia and a melanin-like pigment has been found in the parenchymal liver cells. This disorder is rarely diagnosed in the neonatal period. We report a case of Dubin-Johnson syndrome presenting with neonatal cholestasis.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2009.10a
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• pp.239-239
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• 2009

• Journal of Genetic Medicine
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• v.4 no.2
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• pp.200-203
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• 2007

Niemann-Pick type C is an inborn error of metabolism that affects lipid degradation and storage, which is characterized by hepatosplenomegaly and progressive neurological symptoms. A 7-month-old girl with jaundice was presented cholestasis and hepatosplenomegaly. Laboratory study showed elevated acid phosphatase, angiotensin converting enzyme and mild decrease of cholesterol. Characteristic foamy cell and sea-blue histiocytes in bone marrow biopsy consistent with Niemann-Pick disease. Niemann-Pick type C was suspected by past medical history and findings of physical examination. Therefore, molecular analysis was performed and found mutations of NPC1 gene. We report the first Korean case of type C Niemann-Pick disease confirmed by mutation analysis.

• Korean Journal of Veterinary Research
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• v.35 no.4
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• pp.659-670
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• 1995

Cyclosporin A extracted from fungus Trichoderma polysporum Rifai and Cyclindrocarpon lucidum Booth serves as an important immunosuppressive drug in transplantation surgery. Systemic treatment with cyclosporin A induces an impairment of the biliary excretion of the bile salts and cholestasis. This study was designed to observe the Ultrastural changes of the hepatocytes and the bile canaliculi in cyclosporin A-induced intrahepatic cholestasis in rats. Cyclosporin A was injected into male Wistar rats intraperitoneally 50mg per kg body weight and rats were necropsied at 1, 3, 6, 9, 12, 24 hours. The liver tissues were observed with transmission and scanning electron microscopes and the results were as follows. Transmission electron microscopy: After cyclosporin A injection, SER and lysosomes were increased in the hepatocytes until 9 hours. At 12 hours after injection of cyclosporin A, RER with dilated cistern were increased, and SER, lysosomes in the cytoplasm were decreased. From 1 hour to 24 hours after injection of cyclosporin A, there were dilation of bile canalliculi and decreased or lost microvilli. At 24 hours the dilation of bile canaliculi were decreased. Scanning electron microsocopy: After cyclosporin A injection, the bile canaliculi were dilated and the microvilli were shortened, decreased or lost according to the sites. At 24 hours, the microvilli packing the bile canaliculi were observed. These observations suggest that cyclosporin A-induced cholestasis is associated with the dilation of bile canaliculi, increased microfilaments of the pericanalicular region and decreased or lost microvilli.

• Neonatal Medicine
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• v.16 no.2
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• pp.197-204
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• 2009

Purpose: The objective of this study was to describe the frequency of hepatobiliary dysfunction (HD) at our hospital and determine the possible risk factors and complications associated with the development of HD in very low birth weight infants (VLBWI) treated with parenteral nutrition (PN). Methods: A retrospective study of VLBWI (n=92) that required PN between 2004 and 2008 in the NICU at the Bucheon St. Marys Hospital of Catholic University was performed. HD was defined by a direct bilirubin (DB) >2 mg and a transaminase of 60 IU/L defined cholestasis and liver injury. Groups I, II, and III were limited to cases of cholestasis, liver injury without cholestasis, and no abnormalities, respectively. The VLBWI were compared to each other. Results: Thirty-six subjects (39.1%) had cholestasis and 51 (55.4%) had liver injury. In addition, 36 (39.1%), 19 (20.7%), and 37 (40.2%) subjects were classified as groups I, II, and III, respectively. The three groups showed significant differences in gestational age, 1- and 5-minute Apgar scores, use of surfactant, duration of parenteral nutrition, frequency of RBC transfusions, bronchopulmonary dysplasia (BPD), and patent ductus arteriosus (PDA) (P<0.05). The multiple regression analysis with cholestasis as the dependent variable, showed a significant correlation with gestational age, use of surfactant, frequency of RBC transfusions, and PDA. Conclusion: Various factors, such as birth weight, gestational age, 1- and 5-minute Apgar scores, use of surfactant for respiratory distress syndrome (RDS), frequency of RBC transfusions, BPD, and PDA may be related to hepatobiliary dysfunction in VLBWI treated with PN.