• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.2
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• pp.201-206
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• 2019

Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.2
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• pp.219-229
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• 2016

Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using $^1H$ nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in ${\beta}$-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, ${\gamma}$-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.3
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• pp.168-174
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• 2015

Purpose: Recent studies have suggested that decreased serum potassium level may contribute to various metabolic disorders in adult patients including nonalcoholic fatty liver disease (NAFLD). We aimed to study the correlation between serum potassium levels and the histologic severity of NAFLD in children. Methods: Pediatric patients with biopsy-proven NAFLD were included in this study. Demographic, clinical, and histopathological data were obtained. Multivariable logistic regression analysis was used to assess whether potassium levels are associated with the presence of nonalcoholic steatohepatitis (NASH) or fibrosis after adjusting for possible confounders. A p-value <0.05 was considered statistically significant. Results: Among 125 biopsies, 49.6% (62) had evidence of NASH while 66.4% (83) had some degree of fibrosis (stage 1-3). Mean serum potassium was significantly lower in NASH group as compared to non-NASH group ($4.4{\pm}0.42mmoL/L$ vs. $4.8{\pm}0.21$, p<0.001). Higher potassium level had negative correlation with presence of steatosis, ballooning, lobular inflammation, fibrosis and NAFLD activity score (p<0.05). On multivariable analysis and after adjusting for the metabolic syndrome and insulin resistance, higher potassium level was significantly associated with lower likelihood of having a histological diagnosis of NASH on biopsy (odds ratio [OR], 0.12; 95% confidence interval [95% CI], 0.05-0.28; p<0.001). Similarly, the likelihood of having fibrosis decreases by 76% for every 0.5 mmoL/L increase in potassium (OR, 0.24; 95% CI, 0.11-0.54; p<0.001). Conclusion: Our study shows an inverse relationship between serum potassium levels and the presence of aggressive disease (NASH and fibrosis) in children with NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.3
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• pp.295-305
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• 2021

Purpose: Hepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels. Methods: This retrospective case series included 12 boys aged 6-17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity. Results: Serum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gamma-glutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count. Conclusion: There was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.2
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• pp.174-179
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• 2020

We present an 8 years old girl who was diagnosed at 6 months of age of Progressive Familial Intrahepatic Cholestasis type 2. Although liver transplantation (LT) was classically considered curative for these patients, cholestasis recurrence with normal gamma-glutamyl transpeptidase (GGT), mediated by anti-bile salt export pump (BSEP) antibodies after LT (auto-antibody Induced BSEP Deficiency, AIBD) has been recently reported. Our patient underwent LT at 14 months. During her evolution, patient presented three episodes of acute rejection. Seven years after the LT, the patient presented pruritus with cholestasis and elevation of liver enzymes with persistent normal GGT. Liver biopsy showed intrahepatic cholestasis and giant-cell transformation with very low BSEP activity. Auto-antibodies against BSEP were detected therefore an AIBD was diagnosed. She was treated with Rituximab and immunoadsorption with resolution of the AIBD. As a complication of the treatment she developed a pneumocystis infection successfully treated with corticoids, cotrimoxazol and anidulafungin.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.112-121
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• 2017

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix $GeneChip^{(R)}$ Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.

• The Korean Journal of Cytopathology
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• v.2 no.2
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• pp.105-110
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• 1991

We report a case of hepatoma with duodenal metastasis in a 53 year-old male patient. Hepatoma was confirmed by fine needle aspiration cytology technique, and duodenal metastasis by gastrofiberscopic biopsy. Duodenal metastasis of hepatoma is rare. We briefly review the role of fine needle aspiration cytology technique in diagnosis of hepatoma.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.7 no.1
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• pp.108-111
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• 2004

Tuberculosis is not a common cause of liver abscess and it is rarely considered in the differential diagnosis of a patient with hepatic mass. We report a case of tuberculous abscess of liver and spleen in a 15-year-old boy who presented with abdominal pain, fever and weight loss. The ultrasonographic and computed tomographic scan of the abdomen revealed multiple cystic lesions in the liver and spleen. Mycobacterium tuberculosis was cultured from the ascitic fluid and biopsy specimen of lymph node. Follow up CT scan of the abdomen after anti-tuberculosis medication for eighteen months showed complete resolution of the cystic lesions with calcified nodules.

• The Korean Journal of Cytopathology
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• v.10 no.1
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• pp.79-84
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• 1999

Osteoclast-like giant cell tumor of the liver is an extremely rare malignancy with poor prognosis. To our knowledge, 5 cases have been reported in English literatures, but there was no report about fine needle aspiration cytologic(FNAC) features. We experienced a case of osteoclast-like giant cell tumor of the liver obtained by computed tomography(CT)-guided FNAC and needle biopsy. The cytologic findings mimicked slant cell tumor of the bone. A large hepatic mass of the left lobe with abdominal wall invasion was found by CT in a 46- year-old female complaining of epigastric pain. The FNAC showed moderately cellular smears consisting of osteoclast-like giant cells and mononuclear cells, which were individually scattered or intermingled in clusters. The osteoclast-like giant cells had abundant cytoplasms and multiple small round nuclei with fine chromatin and distinct nucleoli. The mononuclear cells had moderate amount of cytoplasm and relatively bland-looking oval nuclei with single small nucleoli. All of the cytologic features recapitulated the histologic findings of bland-looking osteoclast-like multinucleated giant cells evenly dispersed throughout the background of mononuclear cell. The immunohistochemical study showed positive reaction for CD68 and vimentin, but negative for cytokeratin in both osteoclast-like slant cells and mononuclear cells.

• Clinical and Experimental Pediatrics
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• v.64 no.1
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• pp.31-36
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• 2021

Background: The diagnosis of esophageal varices (EV) is based on the findings of esophagogastroduodenoscopy (EGD), biopsy, and serum markers. Thus, noninvasive cost-effective tests through which high-risk EV children can be diagnosed are needed. Purpose: This cross-sectional study aimed to identify the noninvasive markers for EV in children with liver cirrhosis. Methods: A total of 98 children with liver cirrhosis were evaluated in this study. The spleen size, platelet count, serum albumin, liver function test results, and risk scores were evaluated prior to endoscopy. The endoscopic investigations aimed to identify the presence of EV and red signs, and determine varices sizes. Results: Endoscopy revealed varices in 43 subjects (43.9%). The spleen size, platelet count, international normalized ratio, aspartate aminotransferase to platelet ratio index (APRI), platelet count to spleen size ratio, and risk score differed significantly between patients with and without EV on univariate analysis; however, the logistic regression analysis showed no differences, indicating that none of these parameters were independently associated with the presence of EV. Conclusion: Platelet count, risk score, platelet count to spleen size, and APRI can be useful tools for the identification of high-risk patients with EV and might reduce the need for invasive methods like EGD.