Co-development of autoimmune hepatitis and Sjögren's syndrome triggered by the administration of herbal medicines.

Autoimmune hepatitis (AIH) has been reported in association with Sjögren's syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co-development of AIH and SS in a 53-year-old woman after the consumption of herbal medicines is described. After admission, the patient complained of dryness in her mouth, and she was subsequently diagnosed with SS, which had not been detected previously. The patient's bilirubin and aminotransferase levels initially decreased following conservative management; however, they later began to progressively increase. A diagnosis of AIH was made based on the scoring system proposed by the International Autoimmune Hepatitis Group. The patient was administered a combination of prednisolone and azathioprine, and the results of follow-up liver-function tests were found to be within the normal range. This is an unusual case of AIH and SS triggered simultaneously by the administration of herbal medicines.

Endoscopic ultrasound-guided biliary drainage with placement of a fully covered metal stent for malignant biliary obstruction.

AIM: To determine the utility of endoscopic ultrasound-guided biliary drainage (EUS-BD) with a fully covered self-expandable metal stent for managing malignant biliary stricture. METHODS: We collected data from 13 patients who presented with malignant biliary obstruction and underwent EUS-BD with a nitinol fully covered self-expandable metal stent when endoscopic retrograde cholangiopancreatography (ERCP) fails. EUS-guided choledochoduodenostomy (EUS-CD) and EUS-guided hepaticogastrostomy (EUS-HG) was performed in 9 patients and 4 patients, respectively. RESULTS: The technical and functional success rate was 92.3% (12/13) and 91.7% (11/12), respectively. Using an intrahepatic approach (EUS-HG, n = 4), there was mild peritonitis (n = 1) and migration of the metal stent to the stomach (n = 1). With an extrahepatic approach (EUS-CD, n = 10), there was pneumoperitoneum (n = 2), migration (n = 2), and mild peritonitis (n = 1). All patients were managed conservatively with antibiotics. During follow-up (range, 1-12 mo), there was re-intervention (4/13 cases, 30.7%) necessitated by stent migration (n = 2) and stent occlusion (n = 2). CONCLUSION: EUS-BD with a nitinol fully covered self-expandable metal stent may be a feasible and effective treatment option in patients with malignant biliary obstruction when ERCP fails.

Effect of Helicobacter pylori Eradication on the Development of Reflux Esophagitis and Gastroesophageal Reflux Symptoms: A Nationwide Multi-Center Prospective Study.

BACKGROUND/AIMS: A two-year, prospective, nationwide multicenter study was undertaken to evaluate the effect of Helicobacter pylori eradication on the development of reflux esophagitis (RE) and gastroesophageal reflux disease (GERD) symptoms in the Korean population. METHODS: In total, 1,489 subjects without RE were enrolled at the outpatient clinics of 12 tertiary hospitals nationwide, and 452 subjects underwent follow-up (F/U) for 2 years to evaluate the development of RE and GERD symptoms. RESULTS: RE was found in 33 subjects (7.3% of 452 subjects) and 14 subjects (7.3% of 192 subjects) during the first and second year of F/U, respectively. H. pylori status was not associated with the development of RE. RE was found in six (9.0%) of 67 H. pylori-negative patients, in 26 (11.2%) of 233 eradicated subjects and in eight (7.0%) of 114 noneradicated subjects (p=0.532). Multivariate analysis showed that age ≥60 years (odds ratio [OR], 7.11; 95% confidence interval [CI], 1.92 to 26.41), alcohol consumption (OR, 4.43; 95% CI, 1.03 to 19.19) and F/U cholesterol levels ≥200 mg/dL (OR, 5.03; 95% CI, 1.32 to 19.17) were significant risk factors for the development of RE. There was no significant difference in the development of GERD symptoms or weight according to H. pylori status during the 2-year F/U. CONCLUSIONS: Eradication of H. pylori did not affect the development of reflux esophagitis or GERD symptoms among patients in outpatient gastroenterology clinics in South Korea.

2',4',6'-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury.

Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1ß, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1ß, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.

Can a small endoscopic sphincterotomy plus a large-balloon dilation reduce the use of mechanical lithotripsy in patients with large bile duct stones?

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) is technically difficult in the patients with large extrahepaic bile duct stones. Small endoscopic sphincterotomy combined with large-balloon dilation (ESLBD) currently seems to be a promising alternative for patients with difficult bile duct stones that cannot be extracted by EST. This study compared the therapeutic benefits and complication rates of ESLBD with those of EST alone. METHODS: This study investigated 149 patients treated for stones (≥10 mm) or multiple stones in the extrahepatic bile duct. The ESLBD group (n = 72) was compared with the conventional EST group (n = 77). Mechanical lithotripsy was performed when the stone could not be removed using a Dormia basket. RESULTS: The two groups did not differ significantly in terms of mean bile duct diameter, common bile duct angulation, and presence of periampullary diverticulum. The ESLBD group compared with the EST-alone group had similar outcomes in terms of overall successful stone removal but showed significant differences in complete stone removal during the first session (87.5 vs. 74.0%; P = 0.036) and the use of mechanical lithotripsy for large bile duct stones (≥15 mm) (17.9 vs. 45.8%; P = 0.026). For the patients with a periampullary diverticulum, ESLBD and EST showed similar results only for efficacy and complications. CONCLUSIONS: The ESLBD technique may be a safe, effective alternative to conventional EST for endoscopic removal of large common bile duct stones, and it can reduce the use of mechanical lithotripsy compared with EST alone.

Association of serum alanine aminotransferase and γ-glutamyltransferase levels within the reference range with metabolic syndrome and nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) has recently been found to be a novel component of metabolic syndrome (MS), which is one of the leading causes of chronic liver disease. The serum alanine aminotransferase (ALT) and ⟨-glutamyltransferase (GGT) levels are suggested to affect liver fat accumulation and insulin resistance. We assessed the associations of serum ALT and GGT concentrations within the reference ranges with MS and NAFLD. METHODS: In total, 1,069 subjects enrolled at the health promotion center of Wonkwang University Hospital were divided into 4 groups according to serum ALT and GGT concentrations levels within the reference ranges. We performed biochemical tests, including liver function tests and lipid profiles, and diagnosed fatty liver by ultrasonography. Associations of ALT and GGT concentrationgrading within the reference range with fatty liver and/or MS were investigated. RESULTS: The presence of MS, its components, and the number of metabolic abnormalities [except for high-density lipoprotein-cholesterol (HDL-C) and fasting blood glucose] increased with the ALT level, while the presence of MS, its components, and the number of metabolic abnormalities (except for HDL-C) increased with the GGT level. The odds ratios for fatty liver and MS increased with the ALT level (P⟨0.001 and P=0.049, respectively) and the GGT level (P=0.044 and P=0.039, respectively). CONCLUSIONS: Serum ALT and GGT concentrations within the reference ranges correlated with the incidence of NAFLD and MS in a dose-dependent manner. There associations need to be confirmed in large, prospective studies.

What are the risk factors for acute suppurative cholangitis caused by common bile duct stones?

BACKGROUND/AIMS: Acute suppurative cholangitis (ASC), a severe form of acute cholangitis, is a life-threatening condition that must be treated with appropriate and timely management. The purpose of this study was to identify the factors that predispose patients to ASC. METHODS: We retrospectively investigated 181 patients (100 men, 81 women; age, 70.66±7.38 years, mean±SD) who were admitted to Wonkwang University Hospital between January 2005 and June 2007 for acute cholangitis with common bile duct (CBD) stones. All patients underwent endoscopic retrograde cholangiopancreatogram to remove the stones. Variables and factors that could be assessed upon admission were analyzed to identify the risk factors for the development of ASC. RESULTS: Of the 181 patients, 44 (24.3%) presented with ASC. On multivariate analysis, the followings were found to be independent risk factors for the development of ASC: impacted common bile duct stone (p=0.010), current smoker status (p=0.008), advanced age (>70 years; p=0.002), and gallstone (p=0.016). The most commonly isolated organisms in bile culture were Enterococcus species, Escherichia coli, and Klebsiella species. CONCLUSIONS: Impacted bile-duct stones, current smoking, advanced age, and gallstones were identified as independent risk factors for the development of ASC in patients with CBD stones. These results suggest that emergency biliary drainage is beneficial in patients with these risk factors.

Nardostachys jatamansi protects against cerulein-induced acute pancreatitis.

OBJECTIVES: Nardostachys jatamansi belonging to the family Valerianaceae has been used as a remedy for stomach and skin ailments in Korea. The effect of N. jatamansi on acute pancreatitis (AP) has not been defined. Therefore, we investigated the effect of N. jatamansi on cerulein-induced AP. METHODS: In the pretreatment group, N. jatamansi was administered orally to mice at 10 and 20 mg/kg for 5 days, and the mice were intraperitoneally injected with the stable cholecystokinin analogue cerulein hourly for 6 hours. In the posttreatment group, cerulein was injected hourly for 6 hours, and N. jatamansi was administered at the indicated time (1, 3, and 5 hours after the first cerulein injection) and dose (10 and 20 mg/kg) during the cerulein injection. Blood samples were taken 6 hours later to determine the serum amylase, the lipase, and the cytokine levels. The pancreas and the lung were rapidly removed for morphologic examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. RESULTS: Nardostachys jatamansi treatment attenuated the AP, as shown by the histological examination results of the pancreas and the lung, reductions in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and messenger RNA expressions of inflammatory mediators. CONCLUSIONS: These results suggest that N. jatamansi attenuates the severity of AP and pancreatitis-associated lung injury.

Gardenia jasminoides protects against cerulein-induced acute pancreatitis.

AIM: To investigate the effect of Gardenia jasminoides (GJ) on cerulein-induced acute pancreatitis (AP) in mice. METHODS: C57BL/6 mice weighing 18-20 g were divided into three groups. (1) Normal saline-treated group, (2) treatment with GJ at a dose of 0.1 g/kg, (3) treatment with GJ at a dose of 1 g/kg. GJ was administered orally (n = 6 per group) for 1 wk. Three hours later, the mice were given an intraperitoneal injection of cerulein (50 microg/kg), a stable cholecystokinin (CCK) analogue, every hour for a total of 6 h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70 degree and prepared for the measurement of tissue myeloperoxidase (MPO) activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR (RT-PCR) and real-time PCR measurements. RESULTS: Treatment with GJ decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with GJ attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION: These results suggest that GJ attenuated the severity of AP as well as pancreatitis-associated lung injury.

Cerebral and pulmonary embolisms after transcatheter arterial chemoembolization for hepatocellular carcinoma.

A cerebral lipiodol embolism is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma. We present a case of cerebral lipiodol embolism that occurred after the third arterial chemoembolization, report the clinical and radiological findings, and review the medical literature.

Clinical usefulness of transpapillary removal of common bile duct stones by frequency doubled double pulse Nd:YAG laser.

AIM: To study the efficacy and the safety of laser lithotripsy without direct visual control by using a balloon catheter in patients with bile duct stones that could not be extracted by standard technique. METHODS: The seventeen patients (7 male and 10 female; mean age 67.8 years) with difficult common bile duct (CBD) stones were not amenable for conventional endoscopic maneuvers such as sphincterotomy and mechanical lithotripsy were included in this study. Laser wavelengths of 532 nm and 1064 nm as a double pulse were applied with pulse energy of 120 mJ. The laser fiber was advanced under fluoroscopic control through the ERCP balloon catheter. Laser lithotripsy was continued until the fragment size seemed to be less than 10 mm. Endoscopic extraction of the stones and fragments was performed with the use of the Dormia basket and balloon catheter. RESULTS: Bile duct clearance was achieved in 15 of 17 patients (88%). The mean number of treatment sessions was 1.7 +/- 0.6. Endoscopic stone removal could not be achieved in 2 patients (7%). Adverse effects were noted in three patients (hemobilia, pancreatitis, and cholangitis). CONCLUSION: The Frequency Doubled Double Pulse Nd:YAG (FREDDY) laser may be an effective and safe technique in treatment of difficult bile duct stones.

The degrees of hepatocyte cytoplasmic expression of hepatitis B core antigen correlate with histologic activity of liver disease in the young patients with chronic hepatitis B infection.

Subcellular localizaton of HBcAg have been found to be related to the activity of liver disease and HBV replication. The aim of this study was to determine whether the degree of expression of HBcAg in the hepatocyte nucleus and cytoplasm reflects the level of viral replication and histological activity in chronic HBV infection. A total of 102 patients with biopsy proven chronic hepatitis B were included. There was a highly significant correlation between the levels of HBV DNA in serum and the degree of expression of HBcAg in the nucleus for HBeAg-positive(p=0.000) and negative patients(p=0.04). There was a highly significant, correlation between the degrees of expression of HBcAg in hepatocyte cytoplasm and histologic activities (p<0.01) for HBeAg-positive patients. The degrees of expression of HBcAg in the hepatocyte cytoplasm correlated positively with the lobular activities (p<0.01), but not correlated with the portal activity and fibrosis for HBeAg-negative patients. In conclusion, in the young patients with chronic B viral hepatitis, the degree of expression of HBcAg in the hepatocyte nucleus may affect viral load, and the degree of expression of HBcAg in the hepatocyte cytoplasm may affect histologic activities of liver disease.

Case of pseudomembranous necrotizing tracheobronchial aspergillosis in an immunocompetent host.

A 44-year-old Korean male died of rapidly progressive respiratory failure and refractory hypoxemia in 8 days after being admitted with a fever and dyspnea. The patient was diagnosed with pseudomembranous necrotizing tracheobronchial aspergillosis by fibroptic bronchoscopy and it was not related to an invasion of the pulmonary parenchyma. To the best of our knowledge, this case represents a patient with pseudomembranous necrotizing tracheobronchial aspergillosis that developed in an immunocompetent host, rapidly resulting in airway obstruction with acute respiratory failure and refractory hypoxemia without an invasion of the pulmonary parenchyma.

[A case of congenital hepatic fibrosis presented with symptom of acute cholangitis].

Congenital hepatic fibrosis (CHF) is an autosomal recessive disease, presenting principally in children or young adults with portal hypertension, and infrequently associated with cholangitis. It is associated with renal malformation and Caroli's disease. The diagnosis of CHF is usually confirmed by its typical histological features. Cholangitis is a severe and frequently fatal complication. We report a 22-year-old man with congenital hepatic fibrosis who showed the cholangitis without radiological features of cystic dilatation or stone of intrahepatic ducts.

[A case of spontaneous biloma complicated with choledocholithiasis and chronic cholecystitis].

A biloma is an encapsulated bile collection outside the biliary tree. Most cases of biloma are caused by iatrogenic injury or trauma. Intrahepatic rupture of the biliary tree due to nontraumatic cause is a rare event. A 68- year-old man was admitted because of abdominal pain and fever. He had no past history of abdominal surgery, instrumentation or trauma. Computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) demonstrated a large subcapsular fluid collection in the right liver associated with choledocholithiasis and cholecystitis. Biloma was confirmed by sono-guided percutaneous needle aspiration and was drained through a pigtail catheter. After the successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient recovered. Here, we report an uncommon case of spontaneous biloma formation in association with choledocholithiasis with a review of literatures.