• The Korean Journal of Pharmacology
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• v.2 no.2
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• pp.3-22
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• 1966

An experimental study was done on rabbits to observe the effects of several anticlonorchial drugs on the pathology of the liver infested with Clonorchis sinensis. After two months of infestation with Clonorchis sinensis by giving $400{\sim}500$ metacercariae by mouth, hexachlorophene, chloroquine 2,2' methylenebis (3,4,6 trichlorophenoxy acetic acid) and Hetol were administered orally and follow up macro-and microscopic studies of the liver pathology were done in 2 to 3 days, one month, 2 months and 3 months after the completion of medications. The results obtained in this study are as follows: 1. In both groups which were administered hexachlorophene piperazine 20mg/kg for seven days or 8mg/kg for 18 days, the macroscopic findings of the liver after 3 months revealed only minimal changes of the color and consistency The histopathological findings were the reduction of fibrosis, pseudolobulation, proliferation and adenomatous hyperplasia of bile ducts, and regeneration of liver parenchyma. 2. In groups which were administered chloroquine phosphate 20mg/kg for 18 days or 40mg/kg for 5 days, and also in groups which were administered dithiazanine iodide 30mg/kg for 18 days or 60mg/kg for 5 days, no significant findings of recovery were observed either macroscopically or microscopically. 3. In the group which was given 20mg/kg of 2,2' methylenebis(3,4,6 trichlorophenoxy acetic acid) for 5 days, prominent healing of the damaged tissues was observed after 2 months, revealing the decrease of fibrous tissue, caliber of bile ducts and adenomatous hyperplasia of the epitherial cells of the bile ducts, and regenerationof liver parenchyma. 4. In the group which was given Hetol 200mg/kg for 5 days, swelling, congestion and eddish-brown discoloration of the liver were noted macroscopically after 3 days of completion of drug administration. Hemorrhage, congestion, necrosis and degeneration of the parenchyma were observed microscopically After 10 days, liver appeared almost normal macroscopically, but marked fat degeneration was noted microscopically. After 2 months, the liver was almost normal in gross appearence with only slight atrophy and also marked healing was observed microscopically, i. e. decrease of fibrous tissue and reduction of the previously enlarged bile duct and the regeneration of the liver parenchyma.

• Korean Journal of Veterinary Research
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• v.23 no.1
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• pp.25-35
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• 1983

In order to assess the diagnostic aid of serum gammaglutamyl transpeptidase values in hepatitis, obstructive jaundice and pancreatitis, four groups of 14 health dogs were subjected to the gastric intubatin of $CCl_4$(1.5ml/kg of body weight), the ligation of common bile duct, the ligation of pancreatic ducts and the injection of chloroform(0.2ml/kg of body weight) in the parenchyma of the pancreas. Some serum enzymes serum glutamic pyruvic transaminase(SGPT), serum glutamic oxalacetic transaminase(SGOT), total bilirubin, amylase and lipase known to be indicative of hepatic and pancreatic diseases were monitored. In comparision of these enzymes, gamma-glutamyl transpeptidase(GGTP) valuers were determined in these dogs before and after the experimental procedures. The results were summarized as follows: 1. In $CCl_4$ intoxication gorup, there were no significant changes in serum GGTP activities(mean: 6.0~14.6 IU/L). 2. In bile duct ligation group, serum GGTP activities shelved marked increases, beginning at postsurgical day 1 and rose the highest mean value(342.7 IU/L) on day 12. Then the activities never approached to the base-line values. 3. After the ligation of pancreatic ducts and the injection of chloroform in the pancreas, serum GGTP activities did not rise throughout the experiment. 4. SGPT:GGTP ratio did not increase in bile duct ligation group, but increase markedly in $ccl_4$ intoxication group. 5. The results indicated that serum GGTP values or SGPT:GGTP ratio could provide valuable indicators for differential diagnosis between hepatobiliary obstruction and hepatocellular disease.

• Journal of Trauma and Injury
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• v.29 no.3
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• pp.93-97
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• 2016

Hepatic duct confluence injury, which is developed by blunt abdominal trauma, is rare. Conventionally, bile duct injury was treated by surgical intervention. In recent decades, however, there had been an increase in radiologic or endoscopic intervention to treat bile duct injury. In a hemodynamically stable patient, endoscopic intervention is considered as the first-line treatment for bile duct injury. A 40 year-old man was transferred to the emergency department of ${\bigcirc}{\bigcirc}$ trauma center after multiple blunt injuries. Contrast-enhanced abdominal computed tomography performed in another hospital showed a liver laceration with active arterial bleeding, fracture of the sacrum and left inferior pubic ramus, and intraperitoneal bladder rupture. The patient presented with hemorrhagic shock because of intra-peritoneal hemorrhage. After resuscitation, angiographic intervention was performed. After angiographic embolization of the liver laceration, emergency laparotomy was performed to repair the bladder injury. However, there was no evidence of bile duct injury on initial laparotomy. On post-trauma day (PTD) 4, the color of intra-abdominal drainage of the patient changed to a greenish hue; bile leakage was revealed on magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP). Bile leakage was detected near the hepatic duct confluence; therefore, a biliary stent was placed into the left hepatic duct. On PTD 37, contrast leakage was still detected but both hepatic ducts were delineated on the second ERCP. Stents were placed into the right and left hepatic ducts. On PTD 71, a third ERCP revealed no contrast leakage; therefore, all stents were removed after 2 weeks (PTD 85). ERCP and biliary stenting could be effective treatment options for hemodynamically stable patients after blunt trauma.

• 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.23 no.4
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• pp.263-270
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• 2019

Hydrogen sulfide is well-known to exhibit anti-inflammatory and cytoprotective activities, and also has protective effects in the liver. This study aimed to examine the protective effect of hydrogen sulfide in rats with hepatic encephalopathy, which was induced by mild bile duct ligation. In this rat model, bile ducts were mildly ligated for 26 days. Rats were treated for the final 5 days with sodium hydrosulfide (NaHS). NaHS ($25{\mu}mol/kg$), 0.5% sodium carboxymethyl cellulose, or silymarin (100 mg/kg) was administered intraperitoneally once per day for 5 consecutive days. Mild bile duct ligation caused hepatotoxicity and inflammation in rats. Intraperitoneal NaHS administration reduced levels of aspartate aminotransferase and alanine aminotransferase, which are indicators of liver disease, compared to levels in the control mild bile duct ligation group. Levels of ammonia, a major causative factor of hepatic encephalopathy, were also significantly decreased. Malondialdehyde, myeloperoxidase, catalase, and tumor necrosis factor-${\alpha}$ levels were measured to confirm antioxidative and anti-inflammatory effects. N-Methyl-D-aspartic acid (NMDA) receptors with neurotoxic activity were assessed for subunit NMDA receptor subtype 2B. Based on these data, NaHS is suggested to exhibit hepatoprotective effects and guard against neurotoxicity through antioxidant and anti-inflammatory actions.

• Journal of Digestive Cancer Research
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• v.2 no.2
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• pp.78-81
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• 2014

Intraductal papillary neoplasm of the bile duct (IPN-B) is a rare disease characterized by multicentric proliferation of adenomatous epithelium within the bile ducts. It has better prognosis because of slow disease progression and high probability of early diagnosis, but also has potential for malignant transformation. Therefore early treatment such as surgical resection has been recommended. There are few reports about nature course of IPN-B without treatment. We report a case of papillary adenoma of intrahepatic duct that transformed into intrahepatic cholangiocarcinoma with 8 years of follow up.

• Journal of the Korean Society of Radiology
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• v.83 no.1
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• pp.224-229
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• 2022

Biliary cast syndrome is an unusual complication in patients who have previously undergone liver transplantation. It occurs in approximately 5%-18% of such patients. Rare cases of biliary cast syndrome in patients without liver transplants have also been reported. The pathogenesis of biliary cast has not been clearly identified, although etiologic factors including post-transplant bile duct damage, ischemia, biliary infection, and presence of a post-operative biliary drainage tube have been proposed. Here we present a case of biliary cast that developed in a 49-year-old male who underwent a non-liver surgery after endoscopic and percutaneous management of common bile duct stone.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.193-204
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• 1995

In order to examine the effect of extrahepatic cholestasis induced by common bile duct ligation on the hepatic function, the pharmacokinetics of antipyrine and d-propranolol were investigated in rats. In addition, in an attempt to observe the degree of direct hepatic injury, light and electron microscopic observations and conventional pathologic test using serum were performed. Five days after common bile duct ligation, antipyrine(15 mg/kg) and d-propranolol(3 mg/kg) were intravenously administrated to the rats, respectively. The total clearances of antipyrine and d-propranolol were significantly(p<0.05) decreased. Because hepatic clearance of antipyrine poorly extracted by the liver and that of d-propranolol highly extracted by the liver are respectively dependent on the hepatic intrinsic clearance and the hepatic blood flow, it may be concluded that extrahepatic cholestasis following five days after common bile duct ligation decreased the hepatic intrinsic clearance and the hepatic blood flow. SGPT, SGOT, cholesterol, bilirubin(total bilirubin, direct bilirubin) and alkaline phosphatase were significantly increased(p<0.05). The proliferation of bile ducts was prominent, and degeneration and necrosis of hepatocytes were observed by light microscope. Also, ultrastructurally, bile canaliculi were containing the amorphous materials and losing microvilli, and SER and RER in hepatocytes were dilated and vacuolated.

• Applied Microscopy
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• v.40 no.2
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• pp.89-99
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• 2010

Fibroblasts are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. Mitochondria produce ATP through oxidative metabolism to provide energy to the cell under physiological conditions. Also, mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence and aging. Alternations in mitochondrial structure and function are early events of programmed cell death or apoptosis and mitochondria appear to be a central regulator of apoptosis in most somatic cell. Clonorchis sinensis, one of the most important parasite of the human bile duct in East Asia, arouses epithelial hyperplasia and ductal fibrosis. Isolated fibroblast from the bile ducts of rats infected by C. sinensis showed increase of cytoplasmic process. In addition, decrease of cellular proliferation was observed in fibroblasts which was isolated from normal rat bile duct and then cultured in media containing C. sinensis excretory-secretory product. However, the effects of C. sinensis infection on the mitochondrial enzyme distribution is not clearly reported yet. Therefore, we investigated the structural change of C. sinensis infected bile duct and mitochondrial enzyme distribution of the cultured fibroblast isolated from the C. sinensis infected rat bile duct. As a result, C. sinensis infected SD rat bile ducts showed the features of chronic clonorchiasis, such as ductal connective and epithelial tissue dilatation, or ductal fibrosis. In addition, fibroblast in ductal connective tissue was damaged by physical effect of fibrotic tissue and chemical stimulation. Immunohistochemically detected mitochondrial electron transferase (ATPase, COXII, Porin) was decreased in C. sinensis infected rat bile duct and cultured fibroblast from infected rat bile duct. It can be hypothesized that the reason why number of electron transferase decrease in fibroblast isolated from the rat bile duct infected with C. sinensis is because dysfunction of electron transport system is occurred mitochondrial dysfunction, increase of ROS (reactive oxygen species) and apoptosis after chemical damage on the cell caused by C. sinensis infection. Overall, C. sinensis infection induces fibrotic change of ductal connective tissue, mutation of cellular metabolism in fibroblast and mitochondrial dysfunction. Consequently, ductal fibrosis inhibits fibroblast proliferation and decreases mitochondrial electron transferase on fibroblast cytoplasm. It was assumed that the structure of bile duct could not normalized and ductal fibrosis was maintained for a long period of time according to fibroblast metamorphosis and death induced by mitochondrial dysfunction.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.3
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• pp.210-213
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• 2016

Primary sclerosing cholangitis (PSC), a rare progressive liver disease characterized by cholestasis and bile duct fibrosis, has no accepted, effective therapy known to delay or arrest its progression. We report a 15 year old female patient diagnosed with PSC and moderate chronic active ulcerative colitis (UC) who achieved normalization of her liver enzymes and bile ducts, and resolution of her UC symptoms with colonic mucosal healing, after treatment with a single drug therapy of the antibiotic oral vancomycin. We postulate that the oral vancomycin may be acting both as an antibiotic by altering the intestinal microbiome and as an immunomodulator. Oral vancomycin may be a promising treatment for PSC that needs to be further studied in randomized trials.