bluuebunny/crossref_metadata_2025 huggingface dataset:
CASE REPORT: Insulin ‐ like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia
Authors: YAMAGUCHI MASAKO , KAMIMURA SEIICHIRO , TAKADA JUNICHI , IWATA KAORU , IIDA TAKESHI , KOBAYASHI KAZUO , NAKANO HAJIME , OKADA YASUHIRO , FUJIIMI SATORU , SOHDA TETSURO , HIZUKA NAOMI
Published: March 2008

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin‐like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour‐associated IGF2.
Gastrin release and gastric acid secretion in the rat infected with either Helicobacter felis or Helicobacter heilmannii
Authors: DANON STEPHEN J , MOSS NATHAN D , LARSSON HÅKAN , ARVIDSSON SUZANNE , OTTOSSON SOULTANA , DIXON MIKE F , LEE ADRIAN
Published: March 2008

Helicobacter pylori infection in humans has been shown to be associated with changes in gastric physiology, including exaggerated basal and meal‐stimulated gastrin levels. This has been suggested to be due to the direct effects of the bacterium through inflammation and its urease enzyme. The gastric bacteria Helicobacter felis and Helicobacter heilmannii colonize the antrum of rats in large numbers and induce no significant inflammatory response. Thus, the direct effect of Helicobacter infection on gastric physiology, independent of gastritis, could be studied. Basal, freely fed and stimulated acid and gastrin levels were recorded from animals infected with H. felis, H. heilmannii or uninfected controls over a 30 week period. No significant difference was found between freely fed gastrin over 7 weeks or fasting gastrin over 24 weeks or basal and stimulated acid over 30 weeks between all three groups. Triple therapy did not alter gastrin or acid output. The antrum of all Helicobacter‐infected rats was well colonized; triple therapy cleared H. felis but not H. heilmannii. Very little inflammation was seen in control or Helicobacter‐infected animals. In conclusion, Helicobacter‐induced effects on gastric physiology are unlikely to be due to direct bacterial effects, but are best explained by other factors (i.e. inflammatory damage).
Spontaneous bacterial peritonitis in fulminant hepatic failure
Authors: PODDAR U , CHAWLA Y , DHIMAN RK , VAIPHEI K , VASISHTA RK , DILAWARI JB
Published: March 2008

Ascites may be associated with fulminant hepatic failure (FHF), but spontaneous bacterial peritonitis (SBP) is an extremely rare complication. We report on two patients with FHF who developed SBP. One patient died and the other recovered.
Sucrose permeability as a meas of detecting diseases of the upper digestive tract
Authors: KAWABATA HIDEHIRO , MEDDINGS JON B , UCHIDA YOSHIHITO , MATSUDA KAZUYA , SASAHARA KATSUYUKI , NISHIOKA MIKIO
Published: March 2008

The healthy gastric epithelium will not allow easy permeation of a disaccharide‐sized molecule such as sucrose. However, during gastric damage, intact sucrose can pass the gastric epithelium and ultimately appear in the urine. We examined the relationship between total urinary sucrose excretion and various diseases. We used 149 patients (105 had upper gastrointestinal disease, 12 had gastric cancer and 32 were normal). Subjects were given a solution containing 100g sucrose in 450 c.c. water. All urine was collected for 7.5 h. The urinary sucrose concentration was determined by anion exchange high‐performance liquid chromatography. Total urinary sucrose excretion was significantly higher in patients with gastric ulcer and those with gastric cancer than in endoscopically normal controls. In the 34 patients with gastric ulcer, the total sucrose excretion was closely correlated with ulcer size. Ulcer location did not affect urinary sucrose excretion. A strong correlation was also observed between sucrose excretion and lesion size in the 12 patients with gastric cancer. The sucrose permeability test may be a relatively sensitive method to detect gastric disease.
Protective action of capsaicin and chilli on haemorrhagic shock‐induced gastric mucosal injury in the rat
Authors: TENG CHOO‐HUA , KANG JIN‐YONG , WEE AILEEN , LEE KOK‐ONN
Published: March 2008

Chilli and its pungent ingredient, capsaicin, have been shown to protect against experimental gastric mucosal injury induced by various necrotizing agents such as ethanol and aspirin and stress. We investigated the effect of capsaicin and long‐term ingestion of chilli on haemorrhagic shock‐induced gastric mucosal injury in the rat. Anaesthetized male Sprague‐Dawley rats were subjected to haemorrhagic shock by withdrawing blood to reduce the mean arterial blood pressure to 30–40 mmHg with subsequent reinfusion of shed blood. This resulted in gastric mucosal injury with readily identifiable haemorrhagic lesions. Capsaicin (5mg) administered prior to, but not after, haemorrhagic shock, significantly reduced the gastric mucosal injury in intact animals. Sensory ablation with capsaicin pretreatment (125 mg/kg bodyweight) abolished the gastroprotective effect afforded by capsaicin. Similarly, 4 week intake of chilli powder (360 mg daily) reduced the gastric mucosal injury in intact, but not in capsaicin‐desensitized rats. Capsaicin and long‐term chilli intake protected against haemorrhagic shock‐induced gastric mucosal injury and the protection may be mediated by capsaicin‐sensitive afferent neurons. Our studies are of potential significance in the context of stress ulcer disease in the human.
Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver
Authors: GROSSMAN HOWARD J , WHITE DAVID , GROSSMAN VIRGINIA L , BHATHAL PRITHI S
Published: March 2008

Sublethal injury of the liver with carbon tetrachloride (CCI4) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNγ) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNγ treatment (50 000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCI4. Comparison of biopsies before and after treatment with IFNγ showed that the number of MFB present, identified by their α‐smooth muscle actin immunoreactivity, was markedly reduced. Pressure‐flow curves were constructed in isolated perfused liver preparations from IFNγ‐treated and saline‐treated cirrhotic rats and analysed to obtain the extrapolated zero‐flow intercept (P0, an index of hepatic vascular distensibility) and the vasodilator‐induced change in resistance at a flow rate of 1 mL/min per g (ΔR1 an indication of the level of intrinsic vascular tone). In IFNγ‐treated rats, portal venous pressure measured in vivo was significantly reduced compared with controls (11.9±1.2 vs 16.0 ± 0.5 mmHg, P < 0.05), P0 was lower (2.03 ± 0.18 vs 2.87 ± 0.32 mmHg, P < 0.05) and ΔR1 was decreased (0.39 ± 0.15 vs 1.02 ± 0.19 mmHg/mL per min per g, P < 0.05). The findings indicate that treatment with IFNγ is effective in reducing MFB density in established CCI4‐cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.
Biliary ascariasis complicating endoscopic sphincterotomy for choledocholithiasis in India
Authors: GUPTA ROHIT , AGARWAL DEEPAK K , CHOUDHURI GOUR D , SARASWAT VIVEK A , BAIJAL SANJAY S
Published: March 2008

Endoscopic sphincterotomy is the treatment of choice for patients with choledocholithiasis. Biliary ascariasis has been reported from many parts of the world but is common in Kashmir, India. We report five cases of biliary ascariasis of which four were the result of post‐endoscopic sphincterotomy for choledocholithiasis. Therefore, biliary ascariasis is not an uncommon complication of endoscopic sphincterotomy.
Progress in the endoscopic management of benign biliary strictures
Authors: GIBBONS JOHN C , WILLIAMS STEPHEN J
Published: March 2008

Benign biliary strictures can now be effectively treated with endoscopic therapy in a variety of clinical situations. Despite recent developments in imaging techniques (endoscopic ultrasound and magnetic resonance imaging), it is often difficult to differentiate benign from malignant biliary strictures. The sensitivity of tissue diagnosis (cytology and needle biopsy) at endoscopic retrograde cholangiopancreatography (ERCP) remains poor (40–50%), and further diagnostic methods are required. Endoscopic therapy offers a definitive treatment in 70–90% of patients following post‐operative biliary stricture, including anastomotic strictures following liver transplant. Endoscopic therapy successfully achieves symptomatic, biochemical, and cholangiographic response, and may improve survival in patients with primary sclerosing cholangitis. Strictures secondary to chronic pancreatitis are resistant to standard endoscopic therapy and metallic endoprotheses have been trialed with varying success. Endoscopic therapy is technically difficult and should be performed in specialized centres using a multidisciplinary approach.
Detection of hepatitis C and E virus genomes in sera of patients with acute viral hepatitis and fulminant hepatitis by their simultaneous amplification in PCR
Authors: MADAN K , GOPALKRISHNA V , KAR P , SHARMA JK , DAS UP , DAS BC
Published: March 2008

A study was undertaken to investigate the role of hepatitis C virus (HCV) and hepatitis E virus (HEV), either alone or together, in the causation of sporadic acute viral hepatitis (AVH) and fulminant hepatitis (FH) by simultaneous detection of their genomes in serum samples using the reverse transcription and nested polymerase chain reaction (RT‐PCR). A total of 50 patients were enrolled in the study of which 34 had AVH and 16 had sporadic FH. The serum samples were first tested for hepatitis B surface antigen (HBsAg) and immunoglobulin (Ig)M antibodies against hepatitis A virus (HAV), hepatitis B core antigen (HBcAg) and HEV and also antibodies against HCV using commercially available enzyme‐linked immunosorbent assay (ELISA) kits. All samples were then subjected to RT‐PCR using primers for both HCV and HEV simultaneously in the same reaction mixture. Hepatitis C or hepatitis E was diagnosed when either the antibodies or PCR or both were positive for the respective viruses. Evidence of hepatitis C was present in six of the 34 (17.6%) cases of AVH and two out of 16 (12.5%) cases of FH. Four patients in the AVH group and one of the fulminant hepatic failure (FHF) group were found to be positive by PCR and the rest by serology. But as a sole aetiological agent, HCV infection was found in only one (2.9%) case of AVH and in none of the FHF cases. Evidence of HEV infection was found in 22/34 (64.7%) and 8/16 (50%) cases of AVH and FHF, respectively. Excluding co‐infection with other viruses, HEV was found to be the sole aetiological agent in 15/34 (44.1%) of AVH and 7/16 (43.7%) cases of FHF. In five (10%) (four AVH and one FHF) of the 50 cases, evidence of infection with both HCV and HEV was present. But only in two of these five cases, genomes of both HCV and HEV were co‐amplified. In seven (four AVH and three FHF) out of 50 (14%) cases, no known viral agent could be detected. Our results suggest that HEV is the most common aetiological agent for both acute viral hepatitis and fulminant hepatic failure and that HCV is a rare cause of acute liver diseases although along with other viruses, evidence of either present or past HCV infection may be present in a substantial number of cases. Furthermore, advanced‐stage pregnancy appears to be a potential risk factor for HEV infection and high rate of mortality in women. The study suggests that the method of simultaneous amplification of both HCV and HEV genomes could reduce the time, labour and cost involved in diagnostic work up of acute liver disease patients.
Progression of the proportion of hepatitis B virus precore stop mutant following acute superinfection of hepatitis C
Authors: YEH CHAU‐TING , CHU CHIA‐MING , LIAW YUN‐FAN
Published: March 2008

To examine the progression of the proportion of hepatitis B virus (HBV) precore stop mutant (codon 28 of precore sequence; TGG to TAG) in the viral population of patients with dual hepatitis virus (B and C) infection, a series of serum samples obtained from six cases with chronic hepatitis B with acute hepatitis C superinfection were analysed by the method of amplification‐created restriction site. At the time of superinfection, all patients included in the study were negative for hepatitis B e antigen and positive for its antibody. During the follow up of 30–90 months, in five of the six patients, three different patterns were observed: (i) the proportion of precore stop mutant increased in the first 20 months after acute hepatitis C virus superinfection and then decreased progressively thereafter (two cases); (ii) the proportion of precore stop mutant decreased progressively after superinfaction (two cases); and (iii) no precore stop mutant was found during the course (one case). The remaining patient showed a progressive increase in the proportion of precore stop mutant over a period of 9 months after superinfection. Rather than the progressive increase in the proportion of precore stop mutants during the natural course of chronic HBV infection alone, the results of the present study showed a reverse course of progression following acute hepatitis C virus superinfection. This observation raised the possibility of a preferential or accumulative suppression on precore stop mutant by hepatitis C virus in the later stage of dual infection.
Mortality and rebleeding following Transjugular Intrahepatic Portosystemic Stnt Shunt for variceal haemorrhage
Authors: WILLIAMS DAVID , WAUGH RICHARD , GALLAGHER NEIL , PERKINS KENNETH , DILWORTH PAMELA , DUGGAN ANNE , SELBY WARWICK
Published: March 2008

The present study investigates clinical factors associated with decreased survival following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS). Sixty‐seven patients underwent TIPSS for bleeding related to portal hypertension, 42 (63%) on an urgent basis. TIPSS was successfully placed in 65 (97%) patients with no fatal procedural complications. Thirty day mortality was 21%, there being several predictive factors: transfer from another institution, urgency of procedure, sepsis, encephalopathy, higher mean serum bilirubin and low serum albumin. However, using regression analysis, 30 day mortality was predicted independently only by severe liver disease (Child‐Pugh C, P= 0.003) and older age (P= 0.003). When stratified by Child‐Pugh class, cumulative survival rates at 1 year for class A, B and C were 100, 90 and 34%, respectively. Only three of 25 patient deaths were due to variceal rebleeding. Thirty (46%) patients had a total of 41 rebleeding episodes, with mean time to first rebleed of 4.8 months (range, 3 days‐38 months). Cumulative rebleeding rate at 1 year was 25%. Log‐rank analysis did not reveal a significant difference in overall survival between rebleeders and non‐rebleeders (P= 0.125). When investigated, shunt abnormalities (stenosis, occlusion) were identified in all cases of rebleeding. Our findings confirm TIPSS can be safe and effective in the control of refractory variceal haemorrhage. However, prognosis remains poor for patients with advanced liver disease, particularly if older and in the emergency setting. Vigilant surveillance and high rate of intervention is necessary to maintain shunt patency. Consideration could be given to elective shunt surgery instead of TIPSS for patients with recurrent bleeding and good prognosis liver disease.
Characteristics of hepatocellular carcinoma presenting with variceal bleeding
Authors: CHEN CHIEN‐HUNG , SHEU JIN‐CHUAN , HUANG GUANG‐TARN , LEE HSUAN‐SHU , YANG PEI‐MING , WONG JAU‐MIN , CHEN DING‐SHINN
Published: March 2008

Patients with hepatocellular carcinoma may present with variceal bleeding as the initial symptoms. The aims of this study is to investigate the characteristics of such patients. A total of 1046 hepatocellular carcinoma cases were retrospectively retrieved from our computer records between 1980 and 1993. The medical records and image studies were reviewed. The status of each patient was assessed at the time of presentation. A total of 14 (about 1%) patients with hepatocellular carcinoma presented with variceal bleeding. Five (36%) did not have past history of liver disease. The tumour size ranged from 2.5 to 11.3 cm. Compared with hepatocellular carcinoma patients not presenting with variceal bleeding, these patients had a higher percentage of portal vein thrombosis (57.1 vs 19.4%). In two patients, the hepatic tumours were missed in the initial abdominal sonography. The average survival time was 71 days. Seven patients died within 2 months mainly due to variceal bleeding (41.6%). Variceal bleeding might be a clue to the presence of hepatocellular carcinoma with portal vein thrombosis even in patients without a previous history of liver disease. The tumours in such patients might be the infiltrative type, and thus the portal vein should be carefully worked‐up. Overall, these patients have an extremely poor prognosis. In the management of patients with variceal bleeding, the possibility of hepatocellular carcinoma with portal vein thrombosis should not be overlooked, especially in areas where this cancer is prevalent.
Effect of PGE1 on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats
Authors: MUNTANÉ JORDI , MONTERO JOSE LUIS , MARCHAL TRINIDAD , PEREZ‐SEOANE CARLOS , LOZANO JOSE MANUEL , FRAGA ENRIQUE , PINTADO CARMELO OSCAR , MATA MANUEL DE LA , MIÑO GONZALO
Published: March 2008

Prostaglandin E1 has hepatoprotective properties in several clinical and experimental models of liver dysfunction. Hepatotoxicity induced by D‐galactosamine (D‐GalN) is a suitable animal model of human acute hepatic failure. The aim of the study was to investigate if prostaglandin E1 (PGE1) protection against hepatic D‐GalN‐induced apoptosis was related to tumour necrosis factor‐α (TNF‐α) content in serum. This cytokine is associated with in vitro apoptosis and general inflammatory disorders. In this study, PGE1 was administered 30 min before D‐GalN to rats. In other experiments, several doses of TNF‐α were administered 15 min after PGE1 to D‐GalN‐treated rats. Several parameters related to apoptosis and necrosis were measured by flow cytometry, gel electrophoresis, biochemical analysis, and optical and electron microscopy. Tumour necrosis factor‐α was quantified by competitive enzyme‐linked immunosorbent assay (ELISA). PGE1 by itself did not modify the cell cycle of hepato‐cytes and liver toxicity, but increased TNF‐α in serum in comparison with the control group. D‐Galactosamine increased the percentage of hepatocytes in apoptosis and in the S phase of the cell cycle, and decreased those in G0/G1. Such an increase of hepatocytes in apoptosis was correlated with a higher number of apoptotic bodies and DNA fragmentation in liver than control samples. Also, D‐GalN increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and TNF‐α in serum compared with the control group. Pre‐administration of PGE1 to D‐GalN‐treated rats reduced all the parameters of apoptosis and necrosis in liver, and increased additionally TNF‐α content in serum. In those experiments where low doses of TNF‐α were administered to PGE1 and D‐GalN‐treated rats an inverse relationship appeared between TNF‐α and ALT content in serum. In conclusion, the protective effects of PGE1 on D‐GalN‐induced apoptosis may be linked to its capacity to modulate cell division and/or its immunomodulatory activity. In this sense, our experimental results suggest that TNF‐α could be involved in protection or exacerbation of liver damage in relation to the pathophysiological status of the liver.
p53 expression in gastric mucosa with Helicobacter pylori infection
Authors: KODAMA MASAAKI , FUJIOKA TOSHIO , KODAMA REIJI , TAKAHASHI KENJI , KUBOTA TOSHIHIRO , MURAKAMI KAZUNARI , NASU MASARU
Published: March 2008

Expression of p53 was examined immunohistochemically in the Japanese monkey model with Helicobacter pylori infection of the gastric mucosa to investigate the association between H. pylori infection and gastric carcinogenesis for a period of 4 years. In the course of these observations, from 3 years after H. pylori inoculation, nuclear staining for p53 was seen in the glandular cells of the mucosa infected with H. pylori, especially in the neck region of the glands. There was a gradual increase in the number of immunopositive cases among the infected animals. Three years after inoculation, three out of six cases, and 4 years after inoculation, four out of six cases exhibited positive staining for p53. Before inoculation, and up to 2 years after inoculation, the infected group showed no immunoreaction for p53. The non‐infected group likewise displayed no immunostaining for p53 through 4 years of observation. These results suggest that p53 alterations occur in the H. pylori‐infected gastric mucosa and that H. pylori infection may play an important role in gastric carcinogenesis.
Effect of sucralfate granules in suspension on endoscopic variceal sclerotherapy induced ulcer: Analysis of the factors determining ulcer healing
Authors: YANG WEN‐GUH , HOU MING‐CHIH , LIN HAN‐CHIEH , KUO BENJAMIN ING‐TIEU , LEE FA‐YAUH , CHANG FULL‐YOUNG , LEE SHOU‐DONG
Published: March 2008

Oesophageal ulcers commonly occur after endoscopic variceal sclerotherapy and usually cause complications and a delay in further sclerotherapy. The aims of this study are to investigate the effect of sucralfate granules in suspension on the treatment of endoscopic variceal sclerotherapy induced ulcer and analyse the factors determining the ulcer healing. Fifty‐two patients with oesophageal variceal bleeding received elective endoscopic variceal sclerotherapy. After endoscopically proved oesophageal ulcers, they were randomized to receive either sucralfate granules in suspension (n= 22) or antacid (n= 23). Follow‐up endoscopy was performed weekly. Ulcer healing rates were compared between the groups using the log‐rank test. Forty‐one ulcers receiving sucralfate and 48 ulcers receiving antacid treatment were evaluated. The clinical characteristics of the ulcers were similar in both groups. The ulcers in patients receiving sucralfate healed faster than those receiving antacid (P < 0.02). On analysis of factors affecting ulcer healing, ulcers smaller than 1 cm2 (n= 59) appeared to heal faster than those larger than 1 cm2 (n= 30; P= 0.059) and shallow ulcers (n= 46) healed faster than deep ulcers (n= 43; P < 0.001). On multifactorial analysis, ulcer depth was the only factor determining ulcer healing. The ulcer healing effects of sucralfate became more prominent when the ulcer was larger than 1.0cm2 (1.7±0.6 weeks vs 2.3±0.6 weeks, P= 0.011) and deep (1.7±0.7 weeks vs 2.5±1.0 weeks, P= 0.013) when compared with those receiving antacid. Sucralfate granules in suspension speed the healing of endoscopic variceal sclerotherapy induced ulcer, especially deep and large ulcers.
Rising incidence of oesophageal adenocarcinoma in men in Australia
Authors: LORD REGINALD VN , LAW MATTHEW G , WARD ROBYN L , GILES GRAHAM G , THOMAS ROBERT JS , THURSFIELD VICKY
Published: March 2008

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non‐cardia gastric cancers are decreasing in incidence. Age‐standardized incidence rates for the years 1982–93 for oesophageal adenocarcinoma and non‐adenocarcinoma, and gastric cardia and non‐cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age‐standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance (P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non‐adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non‐adenocarcinoma of the oesophagus. The incidence of non‐cardia stomach cancer continues to fall.
Predictive factors in eradicating hepatitis C virus using a relatively small dose of interferon
Authors: FUKUDA MIZUHO , CHAYAMA KAZUAKI , TSUBOTA AKIHITO , KOBAYASHI MASAHIRO , HASHIMOTO MICHIE , MIYANO YUKIKO , KOIKE HIROMI , KOBAYASHI MARIKO , KOIDA ISAO , ARASE YASUJI , SAITOH SATOSHI , MURASHIMA NAOYA , IKEDA KENJI , KUMADA HIROMITSU
Published: March 2008

Interferon (IFN) can reduce hepatitis C virus load and even eliminate the virus in 30‐40% of patients. Several predictive factors for eradication of the virus have been reported and a higher dose of IFN tends to result in elimination of the virus. However, a small dose of IFN sometimes is as effective as a large dose in eradicating the virus. The predictive factors for such a response are not well established. We retrospectively analysed 50 patients with chronic hepatitis C who were treated with relatively small amounts of IFN (equal or less than 252 million units). Eleven patients were responders (elimination of hepatitis C virus (HCV) and normalization of alanine amino transferase (ALT) for at least 6 months), but the remaining 39 were non‐responders. Multivariate analysis showed that the pretreatment viral load and total dose of IFN per kilogram of bodyweight were significant predictive factors of response to therapy. We also assessed the amino acid substitutions in the IFN sensitivity determining region (ISDR), NS5A codon 2209‐2248, of HCV in serum samples obtained from 31 patients with HCV genotype 1 b. The presence of more than one amino acid substitution in the ISDR tended to correlate with HCV genotype lb elimination. As IFN is expensive and has a number of serious side effects, our study suggests that the optimal dose of IFN may vary from one patient to another and that more stringent criteria should be used to select the optimal dose for therapy.
Clinical significance of serum auto‐antibodies in Chinese patients with chronic hepatitis C: Negative role of serum viral titre and genotype
Authors: LUO JIING‐CHYUAN , HWANG SHINN‐JANG , LI CHUNG‐PIN , LU REI‐HWA , CHAN CHO‐YU , WU JAW‐CHING , CHANG FULL‐YOUNG , LEE SHOU‐DONG
Published: March 2008

Positive serum anti‐nuclear antibody (ANA) and anti‐smooth muscle antibody (SMA) have been reported in 10–66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto‐antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV‐RNA titre and HCV genotype in the presence of serum auto‐antibodies. Serum ANA, SMA and anti‐mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV‐RNA titre and HCV genotype) were compared between patients with and without serum auto‐antibodies. Fifty‐eight (48%) patients were associated with positive serum autoantibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto‐antibodies. Serum HCV‐RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto‐antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto‐antibodies. Hepatitis C virus genotypes and serum HCV‐RNA levels were not correlated to the presence of serum auto‐antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.
CASE REPORT: Alanine aminotransferase deficiency detected in a patient with chronic hepatitis C
Authors: UNO SATORI , KAITO MASAHIKO , KOBAYASHI YOSHINAO , ISHIDA SATOSHI , KATO HIROSHI , GABAZZA ESTEBAN , TAMAKI SHIGENORI , IKOMA JIRO , IMOTO ICHIRO , WATANABE SHOZO , ADACHI YUKIHIKO
Published: March 2008

We report a case of alanine aminotransferase (ALT) deficiency in a 68‐year‐old Japanese female with chronic hepatitis C. The serum was positive for antibody to hepatitis C virus (HCV) and HCV‐RNA. Liver biopsy showed histological evidence of chronic active hepatitis. The level of serum aspartate aminotransferase (sAST) was elevated, but sALT was extremely low. The patient was followed up for her serum aminotransferase levels for 1.5 years under the treatment with ursodeoxycholic acid. The low sALT level persisted during all the follow‐up period. The ALT activity in liver tissue was also decreased. Based on these findings, ALT deficiency was suspected. sALT activity was also found to be low in her two sons. This latter finding suggests the hereditary character of this abnormality.
Characterization of anti‐histone antibodies in patients with type 1 autoimmune hepatitis
Authors: CHEN MING , SHIRAI MUTSUNORI , CZAJA ALBERT J , KUROKOHCHI KAZUTAKA , ARICHI TATSUMI , ARIMA KEIJI , KODAMA TAKAHIRO , NISHIOKA MIKIO
Published: March 2008

We have recently found that antibodies to total histones are common in a group of American patients with type 1 autoimmune hepatitis (AIH). In an attempt to determine the profile and clinical association of anti‐histone antibody (AHA), 45 Japanese AIH patients were studied for serum isotypic reactivity with individual histones (H1, H2A, H2B, H3, H4) by enzyme‐linked immunosorbent assay and western blotting. The results revealed that 40% of sera had reactivities with at least one of individual histones and that the antibodies were detected in all three classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti‐H3 showed the dominant reactivity and it characterized 72% of sera with AHA. The titre of anti‐H3 decreased significantly (P < 0.0075) after steroid therapy and the index of decrease for anti‐H3 was correlated in individuals with that for serum aminotransferase. In general, patients with AHA showed higher serum level of alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher frequency of A2‐DR4 haplotype (53 vs 17%) than their seronegative counterparts. However, the titre of AHA was low in this disease condition and histone class‐specific antibodies did not distinguish patients with distinctive clinical features, although patients with anti‐H3 tended to be younger than those without AHA.
Cystic fibrosis genotypes and alcoholic pancreatitis
Authors: NORTON IAN D , APTE MINOTI V , DIXSON HUGH , TRENT RONALD J , HABER PAUL S , PIROLA ROMANO C , WILSON JEREMY S
Published: March 2008

Pancreatitis and pancreatic insufficiency are associated with both cystic fibrosis and alcoholism. The pathogenesis of alcoholic pancreatitis is unknown, but only a minority of alcoholics develop pancreatitis, and it has been suggested that a genetic predisposition may play a role in this disease. Two observations led to the hypothesis that this genetic predisposition could result from mutations in the cystic fibrosis gene. First, the prevalence of cystic fibrosis mutations in the Caucasian population (approximately 5%) is similar to the prevalence of pancreatitis among heavy drinkers. Second, in both diseases, pancreatic duct damage is a prominent feature and has been postulated to be the initial site of injury. Therefore, the aim of this study was to determine whether an increased frequency of mutations in the cystic fibrosis gene occurs in alcoholic pancreatitis. The 15 most common cystic fibrosis mutations in a Caucasian community were sought in 24 subjects with alcoholic pancreatitis. None were homozygous or heterozygous for these mutations. These findings suggest that cystic fibrosis mutations are not a major genetic factor predisposing to pancreatic injury in alcoholics.
Helicobacter pylori colonization does not influence the symptomatic response to prokinetic agents in patients with functional dyspepsia
Authors: LU CHING‐LIANG , CHANG FULL‐YOUNG , CHEN TSENG‐SHING , CHEN CHIH‐YEN , JIUN KANG LIH , LEE SHOU‐DONG
Published: March 2008

Functional dyspepsia (FD) is very common, but the pathogenesis of Helicobacter pylori leading to FD is still debated. The aim of this study was first to evaluate the impact of H. pylori colonization on the efficacy of Paspertase® (a metoclopramide plus exogenous enzymes regimen for FD patients) and, second, to compare the prevalence of H. pylori infection in FD patients with the general population. Seventy‐four consecutive FD patients were enrolled undergoing Paspertase® treatment. The symptomatic response was evaluated according to 1–4 scales of six main dyspeptic symptoms (i.e. epigastric pain/discomfort, early satiety, heartburn, nausea/vomiting, abdominal fullness/bloating, and belching). Nine hundred and seventy healthy subjects undergoing a paid physical check‐up were included to study the status of H. pylori colonization. The demographic data and basal symptom scores between 43 H. pylori‐positive and 31 H. pylori‐negative patients were not significantly different. Total and individual symptom scores improved significantly after 4 weeks of Paspertase® therapy (P < 0.05), irrespective of H. pylori infection. The prevalences of H. pylori were very similar in FD patients and the general population (58.1 vs 58.0%, NS). In conclusion, these observations suggest that H. pylori colonization is not significant in FD patients of Taiwan while a short‐term prokinetic medication is effective for these patients, irrespective of H. pylori status.
Prevalence of Helicobacter pylori in a representative Anglo‐Celtic population of urban Melbourne
Authors: LIN SHAO K , LAMBERT JOHN R , NICHOLSON LESLEY , LUKITO WIDJAJA , WAHLQVIST MARK
Published: March 2008

The aims of this study were to assess the prevalence of Helicobacter pylori and its relationship with different epidemiological factors in an Anglo‐Celtic Australian population in the Melbourne urban area. Two hundred and seventy‐three (120 men and 153 women with a mean age of 55.6 and range of 20 to 80 years) of 396 eligible subjects randomly sampled from the telephone directory were studied. An ELISA technique was used to detect H. pylori immunoglobulin (Ig)G antibody and self‐administered questionnaires were completed. The overall seroprevalence of H. pylori was 38% and increased with age from 18% (20–30 years old) to 53% (over 70 years; P < 0.0001). The acquisition of H. pylori infection was 1% per year. The prevalence of H. pylori was 48% in men and 30% in women (P < 0.01). The frequency of H. pylori was also associated with low‐income levels and current smoking, but was not associated with peptic ulcer disease history. The prevalence of H. pylori infection in a representative Australian population was found to be similar to other developed countries. The risk factors for H. pylori infection include age, male sex, low household income and a smoking habit. No correlation between H. pylori status and dyspepsia symptoms were observed.
A comparison of transnasal and transoral oesophagogastroduodenoscopy*
Authors: BAMPTON PA , REID DP , JOHNSON RD , FITCH RJ , DENT J
Published: March 2008

Transnasal oesophagogastroduodenoscopy (OGD) with a narrow‐bore endoscope has been demonstrated to be feasible in unsedated volunteers. The aim of the study was to compare efficacy, safety, patient tolerance and costs between this novel approach to OGD and standard sedated OGD. Sixty day patients were enrolled for either sedated transoral endoscopy with a standard calibre endoscope or for unsedated transnasal endoscopy with a narrow‐bore (5.3mm diameter) endoscope. Visualization was unsatisfactory in one examination in each group. The only complications were minor epistaxis in four of the transnasal group and oxygen desaturation below 90% in two of the sedated transoral group. On a 1 (very uncomfortable) to 5 (very comfortable) visual analogue scale, the mean transnasal group score was 3.09, compared with 3.86 in the transoral group (P = 0.013). In the transnasal group, mean procedure room time was 15 min compared with 20 min in the transoral group (P < 0.0003), and mean recovery room time was 7 min compared with 37 min (P < 0.0001). Consumable and pharmaceutical costs were reduced by 65 and 92%, respectively. This study demonstrates that unsedated transnasal OGD is a safe and effective route for OGD and has acceptable patient tolerance. The safety and decreased recovery times offer major cost savings and the potential for this method of OGD to become an office procedure for the investigation of the upper gastrointestinal tract.
CASE REPORT: Hypoechoic submucosal nodules: A sign of Epstein‐Barr virus‐associated early gastric cancer
Authors: NISHIKAWA JUN , YANAI HIDEO , MIZUGAKI YUZO , TAKADA KENZO , TADA MASAHIRO , OKITA KIWAMU
Published: March 2008

The Epstein‐Barr virus (EBV) has been reported to be detectable in about 10% of gastric carcinomas. We performed a comparative study of endosonographic findings of EBV‐positive and ‐negative early gastric carcinomas. Epstein‐Barr virus was detected in 11.8% (four of 34) of endosonographically observed early gastric carcinoma lesions. Endoscopic ultrasonography (EUS) revealed a hypoechoic mass in the third layer, which reflected submucosal nodules, in 75% (three of four) of EBV‐associated lesions. Endoscopically, in 66.7% (two of three) of EBV‐associated carcinomas, the depressed lesion was surrounded by a raised margin covered with normal mucosa and was similar to a submucosal tumour (P < 0.05). Histologically, all three cases of EBV‐associated lesions with submucosai tumour invasion had submucosal nodules of carcinoma with lymphoid stroma and 75% (three of four) were located in the gastric body. The ratio of maximal thickness to width of EBV‐associated lesions was significantly larger than that of EBV‐negative lesions, and this tendency was marked in lesions with submucosal rumour invasion (P < 0.05). This study indicated that EUS and endoscopy are of great use for the determination of EBV association with early gastric carcinoma.
Serum N‐acetylglucosaminyltransferase III activities in hepatocellular carcinoma
Authors: MORI SHIGEKI , AOYAGI YUTAKA , YANAGI MASAHIKO , SUZUKI YASUFUMI , ASAKURA HITOSHI
Published: March 2008

N‐Acetylglucosaminyltransferase III (GnT III) catalyses the addition of N‐acetylglucosamine through a β 1–4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin A (Con A)‐reactive glycan into a non‐reactive state. In this study, we measured GnT III activity to evaluate its diagnostic efficacy and its therapeutic effect on hepatocellular carcinoma (HCC). Concanavalin A‐non‐reactive fraction of serum transferrin (Tf) was also determined since the sugar chains of Tf are one of the possible candidates for the product of GnT III. Serum samples (159) were used from patients with HCC (89), liver cirrhosis (30), chronic hepatitis (19), alpha‐fetoprotein (AFP) producing gastric carcinoma metastatic to the liver (five) and healthy controls (16). N‐Acetyl‐glucosaminyltransferase III activity was determined by high performance liquid chromatography. The reactivity of serum Tf to Con A was also analysed in 21 paired HCC samples before and after treatment by crossed immuno‐affinoelectrophoresis. N‐Acetylglucosaminyltransferase III activity from the HCC group (153 ± 72 pmol/mL/h) was significantly higher than that from liver cirrhosis (99 ± 67 pmol/mL per h), chronic hepatitis (84 ± 39pmol/mL per h) and the normal controls (62 ± 16pmol/mL per h). N‐Acetylgiucosaminyltransferase III activity of 21 patients with HCC was significantly reduced after treatment such as transcatheter arterial chemoembolization and/or percutaneous ethanol infection therapy, (123 ± 77 to 100 ± 60pmol/mL per h). Commensurate decreases of AFP and des‐γ‐carboxy prothrombin with GnT III activity were also observed after treatment. The Con A‐non‐reactive fraction (n= 21; 6.4 ± 2.3%) in patients with HCC after treatment was significantly lower than before (8.2 ± 2.4%). The present study suggests that GnT III activity is a possible and in the diagnosis and evaluation of HCC, especially when other tumour markers are negative.
Involvement of growth factor receptor‐bound protein‐2 in rat hepatocyte growth
Authors: WADA SHIGEO , SASAKI YUTAKA , HORIMOTO MASAYOSHI , ITO TOSHIFUMI , ITO YOSHIKI , TANAKA YOSHIO , TOYAMA TAKASHI , KASAHARA AKINORI , HAYASHI NORIO , HORI MASATSUGU
Published: March 2008

Growth factor receptor‐bound protein‐2 (GRB‐2) is a protein linking receptor tyrosine kinase and Sos (Son of Sevenless gene; Ras GDP/GTP exchange protein), leading to activation of the Ras‐mitogen‐activated protein kinase (MAPK) cascade. So far, it remains unclear how GRB‐2 plays a role in signal transduction pathways evoked by hepatotrophic factors. This study was attempted to evaluate the involvement of GRB‐2 in signalling in rat hepatocyte growth. Using rat cultured hepatocytes stimulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB‐2‐mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynamin‐II by immunoprecipitation and western blot analysis. In primary cultured hepatocytes stimulated with hepatocyte growth factor (HGF) or epidermal growth factor (EGF), GRB‐2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen‐activated protein kinase (MAPK) cascade. In contrast, in primary cultured hepatocytes stimulated with insulin, GRB‐2 linked insulin receptor substrate‐1 (IRS‐1) to dynamin‐II as well as Sos. In the early phase after PH, GRB‐2 activated the Ras‐MAPK cascade by linking HGF receptor, IRS‐1, or EGF receptor to Sos. In the late phase after PH, a complex of IRS‐1‐GRB‐2 associated with dynamin‐II, indicating that GRB‐2 may transduce signals from IRS‐1 to dynamin‐II. We conclude that GRB‐2 may play a role in transmitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.
Regulation of alkaline phosphatase gene expression in human hepatoma cells by bile acids
Authors: KHAN KHALEQUE NEWAZ , TSUTSUMI TAKUYA , NAKATA KEISUKE , NAKAO KAZUHIKO , KATO YUJI , NAGATAKI SHIGENOBU
Published: March 2008

Bile acid‐dependent secretion and the translationally regulated synthesis of alkaline phosphatase (ALP) in rat liver cell culture and by bile duct ligation has already been demonstrated. With the advent of ALP cDNA cloned sequences, the mechanism of the effect of bile acids on ALP activity and the expression of the ALP gene in different hepatoma cells was investigated. The HuH7 and HepG2 cells were treated with taurine‐conjugated cholic acid (CA), chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) at 0–1mmol/L and the numbers of viable cells were counted at 24, 48 and 72h after treatment. A [3H]‐thymidine incorporation study was performed with different bile acids at a concentration of 1 mmol/L for 48h. The cellular activity of ALP in HuH7 and HepG2 cells by bile acids was measured by a substrate‐specific enzymatic assay. To elucidate the effects of bile acids on ALP gene expression, a northern blotting experiment using hybridization with mouse placental ALP cDNA was performed. Cellular ALP activity was time‐ and dose‐dependently increased in both HuH7 and HepG2 cells treated by CA and CDCA; however, no change in ALP activity was observed following treatment with UDCA compared with controls. Induction of ALP activity was dominant in HepG2 cells and independent of cell growth and proliferation. The addition of UDCA synergistically reduced the increased activity of ALP produced by CA and CDCA in both HuH7 and HepG2 cells. By northern blot analysis, the level of ALP mRNA was elevated by CA and CDCA; however, levels of ALP mRNA were suppressed by UDCA. In conclusion, CA and CDCA cause up‐regulation of ALP mRNA and UDCA leads to down‐regulation of ALP mRNA by its interaction with either CA or CDCA. We assume that increased ALP synthesis in hepatoma cells after bile acid treatment results from an enhanced rate of transcription rather than translation of mRNA.
Prognostic significance of pathological and biological factors in hepatocellular carcinoma
Authors: NG IRENE OL
Published: March 2008

Prognostic factors in hepatocellular carcinoma (HCC) conventionally consist of staging with the tumour node metastasis system and grading by tumour cellular differentiation. There are also other factors useful in prognostication but most of them are clinical. With new discoveries in the pathobiology of cancers and introduction of new medical technology, pathological and biological factors of HCC in relation to prognosis have been studied quite extensively. Morphological features of the tumour, both gross and histological, have been found to be significantly related to tumour recurrence and patient survival. Recently, applications of new antibodies and techniques have enabled studies on cellular proliferation using different antibodies such as those for proliferating cell nuclear antigen and Ki‐67 protein. These studies on cellular proliferation, as well as assessment of argyrophilic nucleolar organizing regions, have been shown to provide good prognostic significance. Flow cytometric studies on DNA ploidy and studies on expression of genes including the p53 gene, hormone receptors and others show less unanimous results in their prognostic significance. The influence of gender on survival is also reviewed. In conclusion, pathological and biological factors are useful and help to guide clinicians in the management of patients and in assessment of long‐term prognosis.