• The Journal of Internal Korean Medicine
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• v.22 no.2
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• pp.251-256
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• 2001

In western medicine, there are some reports about herbal medicine induced hepatitis, but in oriental medicine, there are few reports about that. We experienced one case of drug acute cholestatic-hepatitis in the treatment of oriental medicine for HNP. We treated the patient with acupuncture, physical therapy and herb medicine. The patient's symptoms improved after two weeks of treatment. In the course of treatment, the patient intermittently complained of general weakness, nausea, yellowish urin, dyspepsia, and abdominal discomfort. We recognized that total bilirubin(7.2mg/dl), direct bilirubin(5.5mg/dl), serum transaminase(AST 360U/L, ALT 354U/L), alkaline phosphatase(16.6 K/A), urobilinogen(++) and bilirubin(++) were elevated. We diagnosed drug induced hepatitis. We stopped giving herb medicine and began giving Saeng gan gunbi-tang and Injin-oryung-san. Saeng gan gunbi-tang and Injin-oryung-san have been used to treat hepatic disease and have been known to have beneficial effects. After 3weeks on medication, the clinical symptoms and liver function improved. So, we report this case to bring more attention to the safety and toxicity of herbal medicine.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.16 no.4
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• pp.273-278
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• 2013

We present a case of a 7-year-old boy who had cholestasis after trimethoprim-sulfamethoxazole combination therapy. Liver biopsy was performed 36 days after the onset of jaundice because of no evidence of improving cholestasis. Liver histology revealed portal inflammation, bile plug, and biliary stasis around the central vein with the loss of the interlobular bile ducts. Immunohistochemical stains for cytokeratin 7 and 19 were negative. These findings were consistent with those of vanishing bile duct syndrome (VBDS). Chlestasis was progressively improved with dose increment of urosodeoxycholic acid from conventional to high dose. This is the first case report of trimethoprime-sulfamethoxazole associated VBDS in Korean children. The case suggests that differential diagnosis of VBDS should be considered in case of progressive cholestatic hepatitis with elevation of alkaline phosphatase and gamma-glutamyl transpeptidase after or during taking medicine to treat nonhepatobiliary diseases illness.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.121-127
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• 2000

Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver diseases. The objective of this study was to determine the role of lipid peroxidation and glutathione on the bile acid-induced hepatic cell death mechanism in primary cultured rat hepatocytes. To induce hepatic cell death, we incubated primary cultured rat hepatocytes with glycochenodeoxycholic acid $(GCDC;\;0{\sim}400\;{\mu}M)$ for 3 hours. In electron microscopic examination and agarose gel electrophoresis, low concentration of GCDC treatment mainly induced apoptotic feature. Whereas $400\;{\mu}M$ GCDC treated cells demonstrated both apoptosis and necrosis. Lipid peroxidation was increased dose-dependently in GCDC treated hepatocyte. And this was also accompanied by decreased glutathione. Therefore, oxygen free radical damage may play a partial role in GCDC-induced hepatic cell death.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.1
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• pp.120-124
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• 2001

Sclerosing cholangitis is a chronic cholestatic disease characterized by inflammation and obliterative fibrosis of the bile ducts, leading to biliary cirrhosis and ultimately to liver failure. In children, sclerosing cholangitis is known to be associated with Langerhans cell histiocytosis, as well as with congenital immunodeficiencies and cystic fibrosis. Secondary sclerosing cholangitis is suspected in Langerhans cell histiocytosis with chronic cholestasis, liver dysfunction and portal hypertension. Unlike primary sclerosing cholangitis, the cholangitis associated Langerhans cell histiocytosis is destructive in nature and progresses more rapidly to biliary cirrhosis, therefore uniformly the prognosis is poor. In this setting, liver transplantation should be considered early in children with sclerosing cholangitis complicating Langerhans cell histiocytosis before end-stage liver failure and variceal bleeding. We experienced a case of secondary sclerosing cholangitis in Langerhans cell histiocytosis in a 2-year-old boy. We report this case with brief review of the related literatures.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• BMB Reports
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• v.49 no.2
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• pp.105-110
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• 2016

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.481-488
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• 1995

In oriental folk medicine, Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used for more than 20 years as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. Various biochemical and morphological changes including biliary epithelial and parenchymal cell necrosis occur in the liver of animals treated with ANIT. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of secretion volume and total bile acids level in bile juice, and that of serum AST, ALT, ALP, bilirubin, and glucose levels in rat. AMWE stimulated bile secretion and recovered ANIT-induced cholestasis. Bile acid concentrations increased to more than 60% compared with normal by ANIT, which were returned toward normal value with AMWE treatment. Serum AST and ALT activities were increased by ANIT and yet which were significantly decreased with AMWE treatment. In addition, this effect was apparent in AMWE pretreatment group. Serum glucose levels were increased with AMWE and ANIT, while were decreased compared with control in AMWE posttreatment group. Increased serum total bilirubin contents and ALP activities by ANIT were significantly decreased with AMWE posttreatment. In conclusion, AMWE exerted bile acid-independent choleresis effect and then improved to normal conditions ANIT-induced cholestatic syndromes. Also, AMWE have protective and regenerative effect of hepatocytes in rat.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.2
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• pp.154-163
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• 2021

Purpose: In children overlap of autoimmune hepatitis (AIH) and primary sclerosing cholangitis is labelled as autoimmune sclerosing cholangitis (ASC). The only prospective pediatric study showed a high prevalence of ASC by using endoscopic retrograde cholangiopancreatography. Aims of our study were to find the prevalence of ASC by using magnetic resonance cholangiography (MRC) in AIH and in non-AIH cirrhosis and to compare clinical presentation and outcome of AIH and ASC. Methods: Prospectively we did MRC in 38 children with AIH (cases) and 19 disease controls (Wilson disease). Multiple biliary strictures with proximal dilatation on MRC were taken as definitive changes of ASC. Detail clinical, laboratory parameters, liver histopathology and treatment outcome were recorded. Results: The median age of cases was 11.5 (3-18) years, 22 (57.9%) were girls and 28 (73.7%) were diagnosed as type 1 AIH. MRC was done in 11 children (28.9%) at the time of diagnosis and in 27 (71.1%) after a median follow-up of 2.5 (0.3-10) years. Abnormal MRC changes were seen in 14/38 (36.8%) of AIH and 8/19 (42.1%) of controls. However, definite changes of ASC were present in four (10.5%) children in AIH and none in controls. None of the clinical, laboratory, histological parameters and treatment response were significantly different between ASC and AIH groups. Conclusion: The prevalence of ASC in children with AIH was just 10.5%. We suggest MRC in select group with cholestatic features, inflammatory bowel disease and in those who showed poor response to immunosuppression instead of all children with AIH.

• Journal of Life Science
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• v.12 no.3
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• pp.332-339
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• 2002

The pathogenesis of cholestatic liver injury as well as the modulation of hepatic fibrogenesis is causally associated with involvement of reactive oxygen species and free radical reactions. In this study, we investigated whether flavonoids (fustin, sulfuretin) which were isolated from Rhus verniciflua Stokes (RCS) have antioxidant and antihepatotoxicity effect under the biliary liver fibrosis condition. After surgery (control) and posttreated RCS methanol extract (250mg/kg), ethyl acetate extract (250mg/kg) and flavonoids were administered p.o. 10mg/kg/day in two weeks for control groups. The concentration of clinical parameters and product of hepatic lipid peroxidation and the hydroxyproline content were significantly increased in liver fibrosis developed rats. Among the clinical parameters of serum, value of ALT, AST, SDH, total bilirubin and ${\gamma}$ -GT in posttreated RCS components-group showed significantly lower than in control-group. The content of hydroxyproline in posttreated RCS components-group showed lower than in control group and then the value of MDA in posttreated RCS components-group was also significantly reduced to 40~60% of that in control group. The hepatic xanthine oxidase and aldehyde oxidate activities were posttreated RCS components-group showed significantly lower than in control-group. The hepatic SOD and glutathione peroxidase activities were posttreated RCS components-group showed significantly higher than in control-group. Hence we concluded that active components of fustin and sulfuretin which were isolated from R. verniciflua Stokes were hepatoprotective effect in experimental liver fibrosis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.96-107
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• 2006

Citrin deficiency resulting from mutations of SLC25A13is associated with two major clinical phenotypes; neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 2 citrullinemia (CTLN2). In Korea, 7 cases of citrin deficiency have been diagnosed based on biochemical and molecular findings. Four NICCD cases were identified by newborn screening using MS/MS or presenting symptoms like cholestatic jaundice. They are all males, presenting with conjugated hyperbilirubinemia, elevated liver enzymes, hypoalbuminemia, mild hyperammonemia, elevated citrullin, methionine and threonine. All of them have been spontaneously recovered from hepatic manifestation by the age of 6-8 months. Mutation analysis has been performed using their genomic & cDNAs obtained from skin fibroblasts. They turned out to be compound heterozygotes carrying each of 851del4, IVS11+1G>A, and IVS13+1G>A. Three CTLN2 patients were identified. Two adult male patients presented with a sudden loss of consciousness, seizure, vomiting, hyperammonemia and citrullinemia in their twenties. They carried an IVS13+1G>A, 851del4, and IVS11+1G>A mutant alleles. The other CTLN2 patient was 52 year old female patient, manifesting lethargy, altered consciousness, irritability and hyperammonemia. Similar clinical symptoms had recurred at the delivery of first and second babies in her past medical history. She was managed by hemodialysis and survived with neurological sequellae. Also, we screened the presence of 9 common mutations in 500 Korean newborns using dried blood spot of filter papers. Only a allele carried 854del4 mutation. In conclusion, the entire picture of citrin deficiency in Korea including incidence, genotype, clinical features and natural courses, is still vague at the present time.