• Clinical and Experimental Pediatrics
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• v.49 no.7
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• pp.737-744
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• 2006

Purpose : To assess the usefulness of $^{99m}Tc-DISIDA$ scanning in the early evaluation of neonatal cholestasis and to verify the diagnostic value of this test in the differential diagnosis of biliary atresia. Methods : DISIDA scannings were performed and analyzed in 87 children(58 males and 29 females; age, 18-139 days, mean, 59.1 days) with neonatal cholestasis. Five groups according to the final diagnosis and the results of DISIDA scanning were analyzed by scatter plots using the parameters of age and the level of liver function tests(direct bilirubin, AST, ALT, ALP, GGT). The diagnostic sensitivity, specificity and accuracy of DISIDA scanning in the diagnosis of biliary atresia were compared between a higher bilirubin group and a lower bilirubin group(direct bilirubin level >5 mg/dL vs. <5 mg/dL) decided by the pattern of scatter plots. Results : DISIDA scannings in the diagnosis of biliary atresia were analyzed by high sensitivity(100 percent, 16/16) but lower specificity(70.4 percent, 50/71) and accuracy(75.9 percent, 66/87). False positivity(29.6 percent, 21/71) was higher in patients with a higher direct bilirubin level(42.5 percent for >5 mg/dL vs. 9.7 percent for <5 mg/dL, P<0.01). The age and the level of liver function tests(AST, ALT, ALP, GGT) analyzed by scatter plots revealed neither diagnostic value in predicting final diagnosis nor estimated the accuracy rate of DISIDA scanning in the evaluation of neonatal cholestasis. Conclusion : We suggest that DISIDA scannings should not be routinely used in evaluating neonatal cholestasis with elevated direct bilirubin level(>5 mg/dL), especially if it delays early diagnosis and surgical intervention.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.1
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• pp.61-70
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• 2016

Purpose: Parenteral nutrition (PN)-associated cholestasis (PNAC) is one of the most common complications in very low birth weight infants (VLBWIs). The aim of this study is to evaluate the risk factors of PNAC in VBLWIs. Methods: We retrospectively reviewed the medical records of 322 VLBWIs admitted to the neonatal intensive care unit of our hospital from July 1, 2009 to December 31, 2013. We excluded 72 dead infants; 6 infants were transferred to another hospital, and 57 infants were transferred to our hospital at 2 weeks after birth. The infants were divided into the cholestasis and the non-cholestasis groups. PNAC was defined as a direct bilirubin level of ${\geq}2.0mg/dL$ in infants administered with PN for ${\geq}2weeks$. Results: A total of 187 VLBWI were enrolled in this study; of these, 46 infants developed PNAC. Multivariate logistic regression analysis showed that the risk factors of PNAC in VLBWI were longer duration of antimicrobial use (odds ratio [OR] 4.49, 95% confidence interval [95% CI] 4.42-4.58), longer duration of PN (OR 2.68, 95% CI 2.41-3.00), long-term lack of enteral nutrition (OR 2.89, 95% CI 2.43-3.37), occurrence of necrotizing enterocolitis (OR 2.40, 95% CI 2.16-2.83), and gastrointestinal operation (OR 2.19, 95% CI 2.03-2.58). Conclusion: The results of this study suggest that shorter PN, aggressive enteral nutrition, and appropriate antimicrobial use are important strategies in preventing PNAC.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.270-281
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• 2010

Total parenteral nutrition (TPN) is necessary to neonates in neonatal intensive care unit (NICU) for survival and growth because of impossible of enteral feeding. Long-term TPN can be associated with a broad spectrum of hepatobiliary disorder, ranging from mild hepatic dysfunction to severe end-stage liver disease. Cholestasis developed most commonly in neonate, ursodeoxycholic acid (UDCA) is widely used in adult with cholestatic and non-cholestatic liver diseases but there have been limited data on the effects in neonate with PNAC. This study was performed retrospectively to review all medical histories of the total 30 neonates with was administrated UDCA for treatment to parenteral nutrition associated cholestasis (PNAC) at Chungbuk National University Hospital NICU from April 2002 to December 2008. UDCA was administrated at bilirubin is over 2 mg/dl. The criterias for drug evaluation were included hepatic biochemical marker such as direct bilirubin, total bilirubin, AST, ALT, ALP and GGT, TPN therapy period, cholestasis development period, UDCA treatment period, UDCA dosage and adverse effect. In the results, Post-UDCA treatment significant was decreased direct bilirubin, total bilirubin, AST and ALP (p<0.05), and was decreased GGT (p>0.05) and slightly was increased ALT (p>0.05). Reffective timect biDCA was appear at mean $10.5{\pm}1.3$ days, iDCA administration period was mean $64.4{\pm}5.9$ days, cholestasis period was mean $71.9{\pm}6.4$ days and UDCA dosage was mean $22.9{\pm}0.9$ mg/kg/day. Common adverse effects is diarrhea, 5 patients arised mild diarrhea but it possible also related with increased enteral feeding. In conclusion, iDCA can decrease direct bilirubin that major parameter t bcholestasis and oher hepatic biochemical makers. UDCA is effective on PNAC without any serious side effect and cost-effective. Although no greatly shortening cholestasis period, but can protect to develop into severe liver disease and other complication or death. Based on these result, UDCA is recommended for treatment of cholestasis at direct bilirubin is over 2 mg/dl.

• Environmental Mutagens and Carcinogens
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• v.21 no.1
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• pp.1-8
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• 2001

We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

• 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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.155-159
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• 2015

Citrin deficiency (OMIN #605814) is an autosomal recessive disorder caused by the SLC25A13 gene mutation with abnormal biochemical findings, including increased serum ammonia, citrulline, arginine, galactose, serum threonine-to-serine ratio, serum pancreatic secretory trypsin inhibitor, and alpha-fetoprotein. Citrin deficiency can manifest in three ways: in newborns as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as citrullinemia type 2 (CTLN2) with recurrent hyperammonemia and neuropsychiatric symptoms. We report a 35-day-old asymptomatic patient with citrin deficiency who had abnormal biochemical findings.

• The Korean Journal of Nuclear Medicine
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• v.17 no.1
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• pp.71-78
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• 1983

Twenty-nine patients with neonatal jaundice were evaluated with $^{99m}Tc-HIDA$ cholescin-tigraphy to elucidate its clinical applicability. Scintigraphic results were interpreted by the degree of early hepatic uptake and the presence or absence of radioactivity in the G-I tract. The results are as follows; I) In 18 patents with neonatal hepatitis; 8 of 11 patients with decreased hepatic uptake and all 5 patients with good hepatic uptake showed G-I radioactivity. But, the 2 remainders with poor hepatic extraction were not available for evaluation of neonatal jaundice due to patient's poor hepatic function. 2) In 9 patients, confirmed as biliary obstruction; all showed no G-I radioactivity but 3 of the 9 showed poor hepatic extraction on scan and they were not available for evaluation. 3) All the 2 patients with postoperative cholangitis showed G-I radioactivity on $^{99m}Tc-HIDA$ scan. 4) Relationship between histopathologic findings and $^{99m}Tc-HIDA$ scan; Among 5 patients with biliary cirrhosis 3 showed poor hepatic extraction, the remainders showed decreased and good hepatic uptake respectively. But, the 2 portal fibrosis without cirrhosis and 4 cholestasis showed decreased (4) or good hepatic uptake (2).

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.1
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• pp.60-64
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• 2008

Kabuki syndrome is characterized by peculiar facial features, developmental delay, and mental retardation. Congenital hepatic abnormalities in Kabuki syndrome patients have been sporadically reported in the literature and consist of extrahepatic biliary atresia, neonatal sclerosing cholangitis, and transient neonatal cholestasis. We report here a case of congenital hepatic fibrosis in a patient with Kabuki syndrome. To our knowledge, only one case of congenital hepatic fibrosis has been reported in the setting of Kabuki syndrome.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.1
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• pp.65-69
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• 2008

A two-month-old baby had acholic stool, neonatal hyperbilirubinemia and congenital heart disease. Atresia of the hepatic duct was confirmed by open cholangiography, which showed a non-opacified intrahepatic bile duct. Liver biopsy and the Kasai operation were performed. Because the liver biopsy pathology revealed a paucity of intrahepatic bile ducts, the patient was diagnosed with the Alagille syndrome. We report the case of an infant diagnosed with the Alagille syndrome with atresia of the hepatic duct.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.35-41
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• 2012

Since the causative gene, SLC25A13 which encodes citrin, was discovered in 1999, over 500 cases with citrin deficiency have been identified. Two phenotypes can occur by citrin deficiency, neonatal intrahepatic cholestasis by citrin deficiency (NICCD) and adult-onset type II citrullinemia (CTLN2). Some patients with NICCD develop CTLN2 in their later lives. Although cholestatic jaundice is spontaneously resolved within the first year of life in most cases with NICCD, a few cases experience progressive hepatic failure. In this report, two neonates with severe type of NICCD were described. Both cases exhibited neonatal cholestatic jaundice, hyperammonemia and severe coagulopathy. Of note, plasma citrulline and blood galactose levels were extremely high. Serum ${\alpha}$-fetoprotein, plasma methionine, arginine, and threonine-to-serine ratio were elevated as well. SLC25A13 mutations were found in all the four alleles of both patients. With the commencement of lactose-free formula, coagulopathy and hyperammonemia were resolved, and galactose level was normalized. Currently, no factor has been identified to predict the prognosis of NICCD. More experiences are needed to build up the adequate therapeutic strategies for severe type of NICCD. Our experience, however, indicates that the degree of citrullinemia and galactosemia might reflect the severity.