Decreased S100B expression in chronic liver diseases

BACKGROUND/AIMS: Hepatic innervation in liver diseases is not fully understood. We here evaluated S100B expression as a marker of hepatic nerves in patients with various chronic liver diseases, topographically and semi-quantitatively. METHODS: Liver specimens were obtained from 70 subjects (three controls, and 32 chronic hepatitis B, 14 chronic hepatitis C, 14 liver cirrhosis, and seven hepatocellular carcinoma patients). The hepatic nerve density was calculated based on immunohistochemical staining of S100B protein in the portal tracts and hepatic lobules. S100B mRNA levels were semi-quantitatively assessed as the S100B/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA ratio. RESULTS: The densities of the hepatic nerves in portal tracts of chronic liver diseases were not significantly different from those of normal controls but the hepatic nerve densities in lobular areas of liver cirrhosis were significantly decreased (p = 0.025). Compared to the control, the S100B/GAPDH mRNA ratio was significantly decreased in chronic liver diseases (p = 0.006) and most decreased in chronic hepatitis C patients (p = 0.023). In chronic liver diseases, The S100B/GAPDH mRNA ratio tended to decrease as the fibrosis score > 0 (p = 0.453) but the overall correlation between the S100B/GAPDH mRNA ratio and fibrosis score was not statistically significant (r = 0.061, p = 0.657). CONCLUSIONS: Hepatic innervation is decreased in cirrhotic regenerating nodules compared to the control group and seems to decrease in early stages of fibrosis progression. Further studies are needed to clarify the association between changes of hepatic innervation and chronic liver disease progression.

Clinicopathologic Charateristics and Gallbladder Dysfunction in Patients with Endoscopic Bile Reflux / 이화의대지

OBJECTIVES: To investigate clinicopathologic findings and gallbladder (GB) function in patients with endoscopic bile reflux at outpatients clinic. METHODS: We classified endoscopic bile reflux into two groups by bile reflux index (BRI). Those who scored above 14 were the BRI (+) group, and those below 14 were the BRI (-) group. We analyzed clinical characteristics, endoscopic findings including Helicobacter pylori, GB function by DISIDA scan, and electron microscope (EM) findings of endoscopic bile reflux. And we compared clinicopathologic characteristics and GB function between two groups. RESULTS: Endoscopic bile reflux identified in 9.7% of all cases with gastrointestinal symptoms. There are cholecystectomy in 6.7%, gastrectomy in 2.7%, and GB dysfunction in 20.0%. They had prominent gastrointestinal symptoms with variable endoscopic findings. Foveolar hyperplasia is the most common pathologic finding and H. pylori colonization of the stomach was inhibited in cases of bile reflux gastritis. Bile reflux also had distinguishable ultra-structural changes identifiable by EM. BRI (+) group had more old age, GB dysfunction than BRI (-) group. Clinical symptoms and endoscopic findings did not differ between the two groups of endoscopic bile reflux. CONCLUSION: Endoscopic bile reflux was common findings with young adults (30's) at outpatients clinic. Foveolar hyperplasia is common pathologic finding. GB dysfunction were identified as significant risk factors for BRI (+) group.

Severe steatohepatitis with hepatic decompensation resulting from malnutrition after pancreaticoduodenectomy

The most common finding related to nonalcoholic steatohepatitis is obesity, but a status of severe malnutrition can also induce the steatohepatitis. The authors report a rare case of steatohepatitis leading to hepatic decompensation caused by malnutrition after pancreaticoduodenectomy. A 68-year-old female patient who had been previously diagnosed with pancreatic cancer and had undergone pancreaticoduodenectomy 5 months previously presented with abdominal distension. Routine CT performed 3 months after the surgery revealed severe fatty liver without evidence of tumor recurrence. After undergoing pancreaticoduodenectomy her food intake had reduced, and as a result she had lost 7 kg of body weight over 2 months. At this admission, CT revealed moderate amounts of ascites without tumor recurrence. Furthermore, her albumin and lipid profile levels were markedly decreased, and she had a flapping tremor and slurred speech suggestive of hepatic encephalopathy. Her liver biopsy findings were consistent with steatohepatitis and disclosed macrovesicular steatosis without definite fibrosis. After careful nutritional control, her symptoms disappeared and her laboratory findings improved.

Primary Adenosquamous Cell Carcinoma of the Pancreas: A Case Report with a Review of the Korean Literature

The most common pancreatic cancer is adenocarcinoma. Primary adenosquamous cell carcinoma of the pancreas is very rare and aggressive. A 46-year-old man presented with a 3-month history of dyspepsia and a 7-kg weight loss. The physical examination showed tenderness of the right upper quadrant of the abdomen. There was no jaundice. Amylase and lipase were elevated. CA 19-9 was elevated to 566.7 U/mL. Gastroduodenoscopy showed a hard ulceroinfiltrative mass with a yellowish exudate that bled readily on touch in the second portion of the duodenum. Abdominal computed tomography showed a 7.1 x 6.3-cm heterogeneously enhancing mass in the pancreatic head. The pancreatic mass had invaded the duodenum wall, gastric antrum, and gastroduodenal artery sheath. Fine-needle aspiration biopsy of the pancreatic mass revealed adenosquamous cell carcinoma, anaplastic type. We concluded that an adenosquamous cell carcinoma of pancreas had invaded the duodenal mucosa causing ulceration.

Frequency of Intrahepatic FoxP3+ Regulatory T cells during the Natural Course of Chronic Hepatitis B: An Immunohistochemical Study Using Needle-Biopsied Liver Tissue

BACKGROUND: Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized. METHODS: Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry. RESULTS: The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load. CONCLUSIONS: FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.

Infectious Mononucleosis Hepatitis in Young Adults: Two Case Reports

Infectious mononucleosis due to Epstein-Barr virus (EBV) infection sometimes causes acute hepatitis, which is usually self-limiting with mildly elevated transaminases, but rarely with jaundice. Primary EBV infection in children is usually asymptomatic, but in a small number of healthy individuals, typically young adults, EBV infection results in a clinical syndrome of infectious mononucleosis with hepatitis, with typical symptoms of fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly. EBV is rather uncommonly confirmed as an etiologic agent of acute hepatitis in adults. Here, we report two cases: the first case with acute hepatitis secondary to infectious mononucleosis and a second case, with acute hepatitis secondary to infectious mononucleosis concomitantly infected with hepatitis A. Both cases involved young adults presenting with fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, and atypical lymphocytosis confirmed by serologic tests, liver biopsy and electron microscopic study.

A Case of Lower Gastrointestinal Bleeding with Ileal Ulceration in Scrub Typhus / 대한소화기내시경학회지

Scrub typhus, an acute febrile illness caused by Orientia tsutsugamushi-induced vasculitis, is common in Korea, Asia and Pacific Islands. Endoscopic mucosal lesions or mucosal damages have rarely been reported in Scrub typhus. However, four cases of upper gastrointestinal bleeding, controlled by hemoclipping, in Tsutsugamushi-infected patients have been reported in Korea; although, no case of lower gastrointestinal bleeding in Scrub typhus has been reported. We experienced massive hematochezia in a 77-year-old female patient with Scrub typhus. Special studies, including upper gastroduodenoscopy, colonoscopy, abdominal CT scan, and SMA angiography were performed, but the focus of the bleeding could not be found. An RBC scan showed suspicious small bowel bleeding, but a capsule endoscopy could not reveal the focus of the bleeding focus; however, a colonoscopy showed active bleeding at the terminal ileum, with multiple ileal ulcerations. After conservative therapy, the patient's condition was stable and the hematochezia disappeared.

Sigmoid Diverticular Bleeding Detected by Capsule Endoscopy / 대한소화기내시경학회지

Colonic diverticulosis is small outpouching from the lumen of the colon, and this caused by mucosal herniation. Most patients are asymptomatic, but 5~15% of those affected manifest diverticular bleeding. Because most of them stop bleeding spontaneously, the source of the bleeding can not be found by colonoscopy in 15% of these cases. We report here on a case of sigmoid diverticular bleeding that detected by capsule endoscopy in a 68-year old woman who presented with acute obscure gastrointestinal bleeding.

Emerging Need for Vaccination against Hepatitis A Virus in Patients with Chronic Liver Disease in Korea

Vaccination against hepatitis A virus (HAV) is recommended for patients with chronic liver disease (CLD), but this has been deemed unnecessary in Korea since the immunity against HAV was almost universal in adults. However, this practice has never been reevaluated with respect to the changing incidence of adult acute hepatitis A. We retrospectively reviewed the medical records of 278 patients with acute hepatitis A diagnosed from January 1995 to November 2005 and prospectively tested 419 consecutive CLD patients from July to December 2005 for the presence of IgG anti-HAV. The number of patients with acute hepatitis A has markedly increased recently, and the proportion of adult patients older than 30 yr has been growing from 15.2% during 1995-1999, to 28.4% during 2000-2005 (p=0.019). Among 419 CLD patients, the seroprevalences of IgG anti-HAV were 23.1% for those between 26 and 30 yr, 64% between 31 and 35 yr, and 85.0% between 36 and 40 yr. These data demonstrate that immunity against HAV is no more universal in adult and substantial proportion of adult CLD patients are now at risk of HAV infection in Korea. Therefore, further study on seeking proper strategy of active immunization against HAV is warranted in these populations.

Decreased Hepatic Nerve Fiber Innervation in Patients with Liver Cirrhosis

BACKGROUND/AIMS: Hepatic nerve innervation plays important roles in hepatic metabolism and hemodynamic mechanisms. We compared the distribution patterns of hepatic nerves between normal livers and two liver diseases to elucidate the effects of liver disease on the distribution of hepatic nerves. METHODS: Tissue specimens were obtained by ultrasonography-guided needle biopsies from 10 normal controls, 74 patients with chronic hepatitis (CH), and 35 patients with liver cirrhosis (LC). The obtained specimens were immunohistochemically stained using antibodies for S-100 protein and alpha-smooth-muscle actin (alpha-SMA). The degree of the expression in liver tissues was quantified by manual counting of positively stained nerve fibers under light microscopy. The serum hyaluronic acid level was assayed in all subjects to evaluate hepatic fibrosis. Electron microscopy examinations were also performed. RESULTS: The hepatic nerve innervation was significantly lower in LC than in normal controls, as indicated by S-100 protein staining. alpha-SMA and hyaluronic acid levels were higher in LC and CH than in normal controls. Electron microscopy revealed that unmyelinated nerve fiber bundles in the intralobar connective tissue coursed in the vicinity of hepatic triads. CONCLUSIONS: These results suggest that hepatic nerve innervation can be decreased by hepatic inflammatory responses and/or fibrotic changes in LC patients. Further study is needed to clarify this observation.

Biochemical assessment of protein-calorie malnutrition in hepatic encephalopathy / 대한내과학회지

BACKGROUND: Most patients with hepatic encephalopathy have their protein intake restricted. Therefore, protein-calorie malnutrition becomes more severe and may cause more serious problems, such as infection and poor prognosis. The aim of this study is to determine better biochemical parameters for the assessment of nutritional status in patients with hepatic encephalopathy. METHODS: A total 109 patients (30 normal controls and 79 chronic hepatitis B) were enrolled. 79 patients were divided into three groups: chronic HBV infection (hepatitis group, n=28), liver cirrhosis without past history of hepatic encephalopathy (cirrhosis group, n=27), liver cirrhosis with present or past history of hepatic encephalopathy (encephalopathy group, n=24). Serum albumin, total lymphocyte count, IGF-1, growth hormone, retinol binding protein, leptin and fibronectin were measured. RESULTS: Serum albumin level, total lymphocyte count, IGF-1, and growth hormone were significantly lower in encephalopathy group than other groups (p<0.001, p=0.003, p<0.001, and p<0.001, respectively). However, RBP, leptin, and fibronectin were not different among the groups. The level of serum albumin and IGF-1 were significantly lower in encephalopathy group than cirrhosis group (p=0.002, p<0.001, respectively), but growth hormone was not significantly different between cirrhosis group and encephalopathy group. CONCLUSIONS: The level of serum albumin and IGF-1 may be important parameter for nutritional support in chronic liver disease, especially in patients with hepatic encephalopathy, because the level of serum albumin and IGF-1 relate with hepatic encephalopathy as well as reflect the progression of chronic liver disease.

Clinical and Biochemical Parameters of Nutrition to Predict Hepatic Encephalopathy in Cirrhotic Patients / 대한소화기학회지

BACKGROUND/AIMS: Protein-calorie malnutrition is a common complication in cirrhosis. Protein restriction for the treatment of hepatic encephalopathy (HE) may cause disease progression and poor prognosis. Therefore, we evaluated important clinical parameters for nutritional state in cirrhotic patients with or without HE to predict the development of HE. METHODS: Twenty-two cirrhotic patients were divided into two groups; group A-13 patients without HE and group B-9 patients with HE. Clinical and biochemical parameters, serum proteins {serum albumin, insulin-like growth factor-1 (IGF-1), transferrin, leptin, etc}, immunologic parameters and anthropometry were measured. RESULTS: Child-Pugh score and Model for End-stage Liver Disease (MELD) scale were higher in group B (p<0.01). After correction of various factors affecting nutritional assessment, especially of Child-Pugh score and MELD scale, leptin was higher in group B (p<0.05). There was no difference in anthropometric measurements. Transferrin correlated inversely with MELD scale in group A (p<0.01). IGF-1 correlated inversely with total lymphocyte count in group B (p<0.05). Leptin correlated with Child-Pugh scores, total lymphocyte count and mid-arm muscle cirumference in group A (p<0.05, p<0.05 and p<0.05, respectively), and correlated inversely with CD8 in group B (p<0.05). CONCLUSIONS: Leptin level is higher in patients with HE, and further studies for parameters of nutrition to predict HE in many cirrhotic patients will be needed.

A Case of Colorectal Villous Adenoma Found with PET-CT / 대한소화기내시경학회지

Adenomatous polyp in colorectal area is clinically important as being a precursor of colorectal cancer. Early detection of cancer reduces colorectal cancer mortality. Finding and removing precursor adenomas reduces colorectal cancer incidence especially in high risk groups. FDG-PET/CT is a new imaging technology in which a number of clinical applications has been recognized in oncologic imaging. FDG-PET has been shown to detect a wide variety of tumor foci including lymphoma, melanoma, lung cancer and colorectal cancer. Colorectal adenoma can also be detected by FDG-PET. In this case, we describe a colorectal villous adenoma, which was found by FDG-PET/CT. There was a mass of intensely increased FDG uptake in rectal area. The adenoma was confirmed with sigmoidoscopy and removed by polypectomy.

Small Bowel Metastasis from Breast Cancer: A Case Report / 대한소화기학회지

Breast cancer is a common malignancy in women and frequently metastasizes to various organs such as liver, lung, brain, bone and so on. But metastasis to gastrointestinal tract is rare. We describe a 73-year-old woman with small intestinal metastasis of breast cancer. She was diagnosed as right breast cancer in stage I, received modified radical mastectomy 6 years ago and had been followed up without any evidence of residual disease. During investigation for lower abdominal pain and weight loss of 9 kg, we found a small bowel mass. The histology of the tissue taken from small bowel mass was adenocarcinoma, poorly differentiated. The immunohistochemical stain of this specimen showed 75% positivity of estrogen receptor and 90% positivity of progesterone receptor. This is a case of small bowel metastasis from breast cancer and we report this case with a review of literatures.

A Case of the Hepatocellular Carcinoma during the Pregnancy and Metastasis to the Left Atrium / 대한간학회지

A 28-year-old female with a pregnant state of 29th gestational week was admitted because of nausea and vomiting. MRI showed a huge hepatocellular carcinoma. At the 36th gestational week, a normal delivery was done. Surgery of hepatocellular carcinoma was done at 20 days after delivery. After 22 months from the operation, pulmonary metastasis was found and resection of lung mass was done. About 3 years after resection, a low attenuating nodule was detected in the left atrial chamber of heart. We report a case of hepatocellular carcinoma with metastatic lesions to lung and heart in a pregnant woman.

A Case of Portal Vein Thrombosis Associated with Acute Pancreatitis and Cholangitis / 대한소화기학회지

Portal vein thrombosis is a rare complication accompanied with acute pancreatitis or cholangitis/cholecystitis. The main pathogenesis of portal vein thrombosis in pancreatitis or cholangitis/cholecystitis are suggested to be venous compression by pseudocyst and an imbalance between the blood coagulation and fibrinolysis. In this case report, we experienced a 63 year old male who developed portal vein thrombosis later in the course of the treatment of acute gallstone pancreatitis with cholangitis/cholecystitis without any symptom or sign. The diagnosis of portal vein thrombosis was given on follow up CT scan and serum protein S activity was decreased to 27% in laboratory study. Immediate anticoagulation therapy with heparin and thrombolytic therapy with urokinase and balloon dilatation were performed. Despite the aggressive treatment, complete reperfusion could not be obtained. With oral warfarin anticoagulation, the patient showed no disease progression and was discharged. We report a case of portal vein thrombosis as a complication of acute pancreatitis and cholangitis/cholecystitis with a review of literatures.

A Case of Gastropericardial Fistula as a Complication after Esophagectomy with Esophagogastrostomy for Esophageal Cancer / 대한소화기내시경학회지

The gastric pedicle is commonly used for the reconstruction following the resection of esophageal cancer. We recently experienced a case in which gastric ulcer occurred eighteen months postoperatively. A 60 year-old man complaining of chest pain, dry cough, mild fever and chills was admitted to the emergency room. The patient had a history of esophagectomy and esophagogastrostomy because of esophageal cancer. Chest X-ray and CT scan showed pneumopericardium. Upper GI contrast study showed a fistulous tract between the stomach pedicle and the pericardium. Upper GI endoscopy showed beating heart through the fistulous opening. The patient expired with sepsis on the twenty second days after an emergent operation. Gastropericardial fistula caused by a peptic ulcer perforation after the esophgectomy and esophagogastrostomy operation is a very rare complication and brings a fatal result. Early detection using the chest radiography, electrocardiogram, echocardiography, upper GI study and physical examination, and an immediate treatment are therefore mandatory.

Rapidly Progressing Budd-Chiari Syndrome Complicated by Hepatocellular Carcinoma

Budd-Chiari syndrome (BCS) is a disorder caused by occlusion of the hepatic vein or inferior vena cava. The clinical presentation include abdominal pain, hepatomegaly, ascites, leg edema, collateral venous dilatation of the body trunk, and portal hypertension. In addition, BCS can cause hepatocellular carcinoma (HCC) in some patients, although its pathogenesis is not yet completely understood. The average reported time lag from diagnosis of BCS to full-blown HCC ranges from several years to several decades. Hepatic carcinogenesis in patients with BCS perhaps reflects a prolonged and persistent liver injury in that it occurs in the primary inferior vena cava obstruction rather than the primary hepatic vein thrombosis. Among patients with BCS, membranous obstruction of the vena cava (MOVC) usually presents an insidious and chronic illness, whereas primary hepatic vein thrombosis presents an acute or subacute illness. We experienced a case of a patient with BCS, which progressed rapidly that HCC developed only nine months after the diagnosis of BCS. The factors causing this rapid progression are still unclear and remain to be investigated.

Usefulness of Plasma Tumor M2-Pyruvate Kinase in the Diagnosis of Gastrointestinal Cancer / 대한소화기학회지

BACKGROUND/AIMS: Pyruvate kinase (PK) is a key enzyme of glycolysis. Different isoforms of this enzyme are tissue-specifically expressed (M2-PK, M1-PK, R-PK, L-PK). The concentration of the dimeric M2-PK is increased in a metabolic state of tumor cells. In this case, the dimeric M2-PK is termed Tumor M2-PK. We investigated EDTA-plasma of 73 patients with gastrointestinal (GI) cancer and 61 healthy controls to evaluate its significance in diagnosing GI cancer. METHODS: Plasma Tumor M2-PK was measured using an ELISA assay based on two monoclonal antibodies which specifically react with the dimeric Tumor M2-PK. RESULTS: The sensitivity of Tumor M2-PK was 67.1% for all GI cancers, that of CA 19-9 was 38.4% and that of CEA was 34.3%. The specificity of Tumor M2-PK was 91.8% (cutoff=20 U/mL). Tumor M2-PK showed a high sensitivity in gastric cancer (62.2%), colorectal cancer (66.7%) and bile duct cancer (75.0%). In colorectal cancer, the combination of Tumor M2-PK with CEA resulted in a remarkable increase in the sensitivity (86.2%). The average Tumor M2-PK levels were generally elevated in the metastatic GI cancer patients compared to nonmetastatic patients, especially in stomach cancer with statistical significance (p=0.005). CONCLUSIONS: Tumor M2-PK in EDTA-plasma seems to be a new valuable tumor marker in GI cancer.

The Role of Hepatitis C Virus Core Protein on Liver Fibrogenesis: A Study Using an In Vitro Co-culture System / 대한소화기학회지

BACKGROUND/AIMS: The study of liver fibrogenesis by hepatitis C virus (HCV) has been limited due to the lack of an efficiency in vitro culture systems. In the present study, we investigated whether or not HCV core protein is directly related to liver fibrogenesis through stimulation of hepatic stellate cells (HSC). METHODS: Human and rat HSC were isolated and we established an in vitro co-culture system of a stable HepG2-HCV core cell line which was transfected with HCV core gene and primary HSC. We performed immunocytochemical staining and Western and Northern blot analysis in the stimulated HSC by HCV ocre protein to identify the expression of transforming growth factor beta1 (TGF-beta1), transforming growth factor beta receptor II (TGFbeta R II), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF). The expression of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) in the culture media were measured by zymogram and ELISA, respectively. RESULTS: The expression of TGF-beta1 and CTGF was significantly higher in the stable HepG2-HCV core cell line than in HepG2 cells. Furthermore, the makers related to fibrosis such as alpha-SMA, TGF-beta1, Col I, TGFRII and MMP-2 were highly experssed in the co-culture of stable HepG2-HCV core with HSC. CONCLUSIONS: HCV core protein may play a direct role in the fibrogenesis of chronic liver disease with HCV infection.