bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features of patients with chronic liver disease associated with hepatitis C virus genotype 1a/I in Okinawa, Japan
Authors: SAKUGAWA HIROSHI , NAKASONE HIROKI , KINJO FUKUNORI , SAITO ATSUSHI , KEIDA YOSHIHIDE , KIKUCHI KAORU , OYADOMARI YASUTOMO , ISHIHARA MASAKIYO , NAKASONE KAZUNORI , YOGI SEIRYO , KINJO YUKIHIRO , TAIRA MASAAKI
Published: March 2008

The clinical characteristics of chronic hepatitis C virus (HCV) carriers with HCV genotype 1a/I infection were investigated and compared with those of chronic HCV carriers infected with 1b/II, 2a/III, 2b/IV and the mixed type of infection. We found that 16 of 408 (3.9%) carriers had HCV genotype 1a infection, comprising four of 67 (6.0%) blood donors, 11 of 263 (4.2%) patients with chronic hepatitis and one of 39 (2.6%) patients with liver cirrhosis. Three of 408 subjects had a mixed infection of genotypes 1a/I and 1b/II. All carriers with genotype 1a (including those with the mixed infection) were of Japanese origin and all, except one who was born in Brazil, were born in Okinawa Prefecture. Nine of 14 patients infected with genotype 1a for whom medical records were obtained had a history suggestive of infection through blood exposure; six had had blood transfusions, one had tattoos, one is a nurse and one had a history of drug addiction. There were no haemophiliacs or other multitransfused patients in the genotype 1a group. Of 10 patients infected with genotype 1a who received interferon (IFN) therapy, four (40%) showed a complete response. Although the small number of patients infected with genotype 1a in the present study precluded statistical analysis of the response to IFN, the response in patients with genotype 1a was better than the response in those infected with genotype 1b and poorer than the response in those patients infected with genotype 2a/III or 2b/IV.
CASE REPORT: Endoscopic ultrasonographic findings of mucosal prolapse syndrome
Authors: MOTOMURA YASUAKI , SAKAI KENJI , CHIJIIWA YOSHIHARU
Published: March 2008

A 41‐year‐old man with mucosal prolapse syndrome received endoscopic ultrasonography. The lesion was mildly hypoechoic and irregular, with extension into the muscularis propria and disappearance of the normal mucosal and submucosal layers. In addition, an enlargement of the muscularis propria, bridging towards the mucosal layer with merging of the two layers, was observed. These findings suggest the usefulness of endoscopic ultrasonography in the diagnosis of mucosal prolapse syndrome.
REVIEW: Intrahepatic cholestasis. A puzzling disorder of pregnancy
Authors: REYES HUMBERTO
Published: March 2008

Intrahepatic cholestasis of pregnancy is characterized by skin pruritus and a biochemical cholestasis of mild to moderate severity appearing during pregnancy (mainly in the third trimester) and disappearing after delivery. It recurs in 40–60% of future pregnancies. The intensity of pruritus and the laboratory alterations (increased serum bile salts and transaminases in almost all patients, hyperbilirubinaemia in 20% of patients) fluctuate during one pregnancy and also vary in subsequent affected pregnancies. This disease has no meaningful consequences for the mother; in contrast, it is associated with an increased risk of foetal distress, causing premature deliveries and stillbirths. Cholestasis of pregnancy has been recognized in most countries and ethnic groups but its prevalence is higher in Chile (14% of deliveries in 1975 and approximately 4% in 1995) and in Sweden than in other countries. The cause is unknown. Sex hormones, mainly oestrogens and progesterone, appear to be involved in its pathogenesis. An interplay between a genetic metabolic predisposition and some environmental factor(s) is apparently relevant. Clinical and experimental studies suggest that a marginal selenium deficiency could be a dietary pathogenic factor. Some drugs attenuate pruritus and improve maternal cholestasis, but not the foetal prognosis. Ursodeoxycholic acid (UDCA) administration provides a significant improvement in maternal pruritus and in the biochemical abnormalities, with no adverse effects in the mother or child. Recent clinical and experimental studies show that UDCA administration improves maternal disease and foetal prognosis without any detectable adverse effects.
REVIEW: Hepatitis B and liver transplantation
Authors: ANGUS PETER W
Published: March 2008

Liver transplantation in hepatitis B virus (HBV)‐infected patients is very commonly followed by recurrence of infection in the transplanted liver. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in non‐immuno‐compromized subjects and this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV‐DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti‐HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that are potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine (2′,3′, dideoxy, 3′, thiacytidine) and famciclovir (a guanosine analogue). Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently underway to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of post‐transplant HBV recurrence.
CASE REPORT: Incomplete septal cirrhosis with liver cell dysplasia
Authors: BAIL B LE , BERNARD PH , HERVOUET M , CARLES J , BALABAUD C , BIOULAC‐SAGE P
Published: March 2008

A 60‐year‐old woman was transplanted for end‐stage alcoholic cirrhosis. The diagnosis of cirrhosis was made 13 years earlier on the basis of features of portal hypertension and a wedge liver biopsy. Liver function tests were subnormal except for a low prothrombin time. Unproven possible alcohol abuse was the only aetiological factor. Her condition remained unchanged until transplantation, despite complete abstinence. Histological examination of the explant showed incomplete septal cirrhosis associated with distal obstructive portal venopathy, cirrhotic nodules predominantly in the subcapsular areas and nodular regenerative hyperplasia with septal fibrosis elsewhere. In addition, there were areas of large and small liver cell dysplasia. This observation shows the difficulty in making a diagnosis of incomplete septal cirrhosis and the hypothetical link between liver cell dysplasia (which has never been reported in incomplete septal cirrhosis but is well known to be associated with hepatocellular carcinoma in cirrhosis) and rare cases of liver adenomas and carcinomas reported in patients presenting with liver vascular disorders.
Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma
Authors: CHAO YEE , CHAN WING‐KAI , WANG SUN‐SANG , LAI KWOK‐HUNG , CHI CHIN‐WEN , LIN CHING‐YUANG , CHAN ANN , WHANG‐PENG JACQUELINE , LUI WING‐YIU , LEE SHOU‐DONG
Published: March 2008

This is a report of a phase II study of megestrol acetate (160mg/day, orally) in the treatment of hepatocellular carcinoma (HCC). Forty‐six patients with advanced HCC were studied and tumour response, changes in appetite, bodyweight, a feeling of well‐being, survival and toxicity were evaluated. Thirty‐two patients were able to be evaluated for response; there were no complete responders or partial responders. Twelve patients (38%) had stable disease and seven of these patients had a minor response with a median size reduction in the tumour of 18%. Twenty patients (62%) had progressive disease. Five of 24 (21%) patients had a median reduction in α‐fetoprotein levels of 59ng/mL. The overall median survival was 4 months (range 1 week to 27 months). Twenty of 32 (62%) patients had an increased appetite and feeling of well‐being. Fourteen of 22 (64%) patients had a median lean bodyweight gain of 5 kg (range 1–14 kg). Toxicities were minimal. Tests for glucocorticoid receptors were performed in 10 patients. Four of five patients who were positive for glucocorticoid receptors in the tumour had a stable disease and all five patients who were negative for glucocorticoid receptors had progressive disease. Megestrol acetate had no significant effect on the tumour in HCC patients. However, megestrol acetate is useful in the palliative management of HCC patients, with improvements in appetite, bodyweight and a feeling of well‐being with minimal side effects. Some patients had stable disease, a minor reduction of tumour size and a prolonged survival after megestrol acetate treatment and this response may be related to the presence of glucocorticoid receptors in the HCC tumour.
Ethanol feeding enhances inflammatory cytokine expression in lipopolysaccharide‐induced hepatitis
Authors: PENNINGTON HELEN L , HALL PAULINE DE LA M , WILCE PETER A , WORRALL SIMON
Published: March 2008

Elevated concentrations of plasma tumour necrosis factor (TNF)‐α, interleukin (IL)‐1 and IL‐6 have been detected in patients with alcoholic hepatitis and have been implicated in the pathogenesis of hepatocyte necrosis. The present study used a rat model to conduct a detailed histological and biochemical examination of the expression of various pro‐inflammatory cytokines and associated liver pathology in ethanol‐potentiated lipopolysaccharide (LPS)‐induced liver injury. Male Wistar rats were pair‐fed either the control or ethanol‐containing (36% of caloric intake as ethanol) form of the Lieber‐DeCarli liquid diet for 6 weeks. Liver injury was induced by the i.v. injection of LPS (1 μg/g bodyweight), with animals being killed at 0, 1, 3, 6, 12 and 24 h after injection. At the later time points, plasma transaminase and transpeptidase activities were significantly elevated in ethanol‐fed LPS‐treated rats compared with control‐fed LPS‐treated animals. At these times after LPS treatment, hepatocytes in ethanol‐fed animals displayed fatty change and necrosis with an associated neutrophil polymorph infiltrate. Time course analysis revealed that plasma TNF‐μ (1–3 h post‐LPS) and IL‐6 (3 h post‐LPS) bioactivity was significantly elevated in ethanol‐fed compared with control‐fed animals. No difference was seen in plasma IL‐1μ concentration (maximal in both groups 6 h post‐LPS). The expression of TNF‐μ, IL‐1μ, IL‐1β and IL‐6 mRNA were elevated between 1 and 6 h post‐LPS in the livers of both control and ethanol‐fed rats. However, ethanol‐fed LPS‐treated animals exhibited significantly higher maximal expression of IL‐1 and IL‐6 mRNA. Comparison of the appearance of cytokine mRNA and plasma bioactivity indicated an effect of ethanol feeding on post‐transcriptional processing and/or the kinetics of the circulating cytokines. Elevated levels of both hepatic cytokine mRNA expression and the preceding plasma cytokines are presumably a necessary prerequisite for hepatic injury seen in this model and, therefore, possibly for the damage seen in human alcoholics. Further studies using this model may lead to significant advances in our understanding of the pathogenic mechanisms of alcoholic liver disease in humans.
Enhanced motility of the vagotomized canine stomach by electrical stimulation
Authors: YOKOTA MASAAKI , ANDO NOBUTOSHI , OZAWA SOJI , IMAZU YOSHIHIRO , KITAJIMA MASAKI
Published: March 2008

Functional impairment of the vagotomized stomach used as a substitute oesophagus seriously deteriorates the quality of life of patients following oesophageal cancer surgery. We speculated that if the enteric neurons of the reconstructed gastric tube survived functionally, the motility of the gastric tube could be facilitated and the recovery process after operation would improve as a consequence. In the present study we investigated whether direct electrical stimulation was effective for facilitating the motility of the canine vagotomized stomach. Dogs underwent truncal vagotomy by trahsabdominal approach and, in some cases, arteries to the upper stomach and the oesophagus were also ligated and resected to resemble the blood supply and surgical invasion of the reconstructed gastric tube. Electrical stimulation, a few minutes of positive rectangular current pulses, amplitude 20 V (or 15 mA), duration 0.5 ms and frequency between 0.2 and 7 Hz, was delivered on the greater curvature of the mid corpus. Changes in mechanical contractions were recorded using strain gauge force transducers. Electrical stimulation successfully enhanced the mechanical force of the phasic ring contractions of the vagotomized stomach in a frequency dependent manner. Aboral propagation and periodicity of the contractions, impaired by surgical procedures, were restored during stimulation. These excitatory effects were inhibited by atropine, hexamethonium and tetrodotoxin, suggesting that electrical stimulation acts on intramural cholinergic nerves that have survived functionally. These results suggest that electrical stimulation could be an effective method for improving the motility of the vagotomized stomach.
CASE REPORT: A case of primary ileal carcinoma in a young woman and a review of the Japanese literature
Authors: HORIUCHI A , AKAMATSU T , MUKAWA K , OCHI Y , KIYOSAWA K , SUGIYAMA A , KATSUYAMA T
Published: March 2008

We report a case of primary ileal carcinoma in a young woman, which was diagnosed definitively before operation. A 29‐year‐old woman presented with abdominal pain, diarrhoea and bloody stools. Colonoscopic and radiographic studies revealed that there was a 7.5 × 7 cm tumour (well‐differentiated adenocarcinoma) at the terminal ileum, forming an ulcerated lesion at the centre. The tumour had invaded the caecum, the right urinary tract, the right ovary and a portion of the sigmoid colon. Fifty‐three cases of primary ileal carcinoma were reported in Japan between 1982 and 1994 and their clinical features are reviewed herein.
Some peculiarities of hepatobiliary diseases in Vietnam
Authors: VAN HA MAO
Published: March 2008

The most frequent hepatobiliary diseases in Vietnam are chronic hepatitis and cirrhosis, liver abscess, hepatobiliary ascaridiasis, angiocholitis, biliary lithiasis and primary liver cancer. The principal causes of chronic hepatitis and cirrhosis are HBV and HCV infections. Alcohol and chemicals (drugs, agricultural, industrial, war herbicides) also play an important role. Malaria causes hepatitis and fibrosis lesions, however no cirrhotic lesions were observed. There are two categories of liver abscess, amoebic and cholangitic, often caused by ascaridiasis. Treatment of amoebic abscesses is, at first, non‐surgical for small abscesses, often combined with ultrasound guided abscess puncture. Cholangitis abscesses are more serious and often require surgical intervention. Among the gallstones, only 15% are of the gall‐bladder, the majority are choledocho‐ and intrahepatic‐lithiasis, composed largely of calcium bilirubinate and are frequently caused by Ascaris‐related cholangitis and the nucleation of Ascaris eggs. Forty‐seven per cent of acute cholecystitis are acalculous, showing a higher frequency than in Western countries. Primary liver cancer is one of the most frequent malignancies in Vietnam. More than 90% of liver cancers are hepatocellular carcinomas. The principal causes are HBV infection, followed by HCV infection, aflatoxin, alcohol and chemicals. Recent efforts aiming at earlier diagnosis, by selective screening in high‐risk groups, have used clinical surveillance, abdominal sonography and AFP level determination. Promising results were obtained in prevention trials by reducing the high AFP level of cirrhotic patients using a vegetal drug, Gacavit, and by treatment with percutaneous ethanol injection therapy, as an alternative therapeutic measure for liver tumour resection.
The Gastroenterological Society of Australia
Authors: TOOULI JAMES
Published: March 2008

In this review, a summary of the objectives and activities of The Gastroenterological Society of Australia is given. It illustrates the multidisciplinary and multi‐functional roles of a society that is confident and active in supporting and reflecting the views of its members in the pursuit of excellence in clinical practice, research and education in the various areas of digestive health.
Current topics on digestive disease in Korea
Authors: WAN CHOI KYOO
Published: March 2008

This is a summary of the research topics, of current interest, relating to digestive disease in Korea. This review is based on the subjects of the papers that were accepted for presentation at the 34th Annual Meeting of the Korean Society of Gastroenterology and the 39th Semiannual Meeting of the Korean Society of Gastrointestinal Endoscopy held November 22–24, 1995, in Seoul. The most popular topics were on Helicobacter pylori infection. These included experimental papers on the pathogenesis of bacteria‐associated gastritis and the duodenal ulcer. Recently, the increase in the number of papers published on the motility of the gastrointestinal and pancreaticobiliary tracts is quite remarkable. Molecular genetic works on oncogenesis using cultured tumour cell lines, on the enzyme expression in the biopsied mucosal cells of the small intestine, and on the various expressions of viral genomes in the hepatocytes are among these recent topics of research. Clinical works, such as therapeutic endoscopy in malignant diseases and therapeutic trials in the hepatitis virus‐associated chronic liver diseases are also popular topics.
REVIEW: α1‐Antitrypsin deficiency associated liver disease
Authors: QU DONGFENG , TECKMAN JEFFREY H , PERLMUTTER DAVID H
Published: March 2008

α1‐Antitrypsin (α1‐AT) deficiency is the most common genetic cause of liver disease in children and genetic disease for which children undergo liver transplantation. It also causes cirrhosis and hepatocellular carcinoma in adults. Studies by Sveger in Sweden have shown that only a subgroup of the population with homozygous PiZZ α1‐AT deficiency develop clinically significant liver injury. Other studies have shown that the mutant α1‐AT Z molecule undergoes polymerization in the endoplasmic reticulum and that a subpopulation of α1‐AT‐deficient individuals may be susceptible to liver injury because they also have a trait that reduces the efficiency by which the mutant α1‐AT Z molecule is degraded in the endoplasmic reticulum.
B7‐2 positive cells around interlobular bile ducts in primary biliary cirrhosis and chronic hepatitis C
Authors: KAJI KYOSUKE , TSUNEYAMA KOICHI , NAKANUMA YASUNI , HARADA KEN‐ICHI , SASAKI MOTOKO , KANEKO SHUICHI , KOBAYASHI KEN‐ICHI
Published: March 2008

Bile duct damage in patients with chronic hepatitis C (hepatitis‐associated bile duct lesion) as well as that in patients with primary biliary cirrhosis (PBC; chronic non‐suppurative destructive cholangitis), may be causally related to immunological assaults. Efficient antigen presentation is known to require the provision of a costimulatory signal which is dependent on the CD28 on T cell surfaces, and that at least two molecules, B7‐1 and B7‐2, work as costimulatory ligands for CD28. In this study, we examined immunohistochemically, the expression of B7‐2 in portal tracts of liver biopsy specimens obtained from 75 patients with chronic hepatitis C who had hepatitis‐associated bile duct lesions, and from 63 PBC patients with chronic non‐suppurative destructive cholangitis. B7‐2 positive cells were recognizable as large mononuclear cells scattered in portal tracts. Some of these cells showed a dendritic cell‐like appearance. B7‐2 positive cells were observed more frequently (41%) in PBC liver specimens than in chronic hepatitis C specimens (17%, P< 0.05). In PBC livers, such cells were preferentially observed around the damaged bile duct with a few located in the biliary epithelial layer. There was no such finding in chronic hepatitis C livers. The frequency and density of B7‐2 positive cells in the liver specimens tended to decrease according to the stage of PBC (45% in stages 1 and 2, and 33% in stages 3 and 4; P=0.10), whereas with chronic hepatitis C, no such tendency was observed. These findings suggest that B7‐2 positive cells may play a role in the bile duct lesions that appear in the early histological stages of PBC and that the immunological mechanisms of bile duct damage, particularly of antigen presentation and B7‐2 expression, differ between PBC and chronic hepatitis C.
Different viral aetiology of hepatocellular carcinoma between two hepatitis B and C endemic townships in Taiwan
Authors: LU SHENG‐NAN , CHUE PAY‐YU , CHEN HUI‐CHI , WU MEI‐HUEI , CHEN I‐LUNG , HUANG JEE‐FU , WANG JING‐HOUNG , PENG CHIEN‐FANG , SHIH CHING‐HUA , YOU SAN‐LIN , LU CHIH‐FENG , CHEN CHIEN‐JEN , CHANG WEN‐YU
Published: March 2008

In Taiwan, we found two hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐endemic townships, Paisha and Tzukuan, with an anti‐HCV prevalence of 19 and 37% in men, and 26 and 38% in women, respectively. The hepatitis B surface antigen (HBsAg)‐positive rates were 25 and 18%, for men and women in Paisha, and 25 and 22% in Tzukuan, respectively. According to the national death certification database (1982 to 1991), the annual age‐adjusted mortality rates per 100 000 population for liver cancer among men and women were 83.0 and 13.8, respectively, in Paisha, and 55.9 and 17.0 in Tzukuan compared with 30.9 and 9.1 in Taiwan as a whole. The male‐to‐female ratios were 6.0 in Paisha and 3.3 in Tzukuan. Aetiology of 11 cases of hepatocellular carcinoma (HCC) from Paisha and 14 cases from Tzukuan were analysed. All HCC cases from Paisha were HBsAg positive, while 13/14 HCC cases from Tzukuan were anti‐HCV positive. The endemic duration of HCV in Tzukuan seemed long enough to induce HCC, but the HCV appeared to be a newly introduced infection in Paisha.
Case Report: Interferon induced coma in Sheehan's syndrome
Authors: MABE KATSUHIRO , SHINZAWA HARUHIDE , YAMATANI KEIICHI , TAKEDA TADASHI , ISHIBASHI MASAMICHI , YAMADA NOBUO , MISAWA HIROYUKI , WAKABAYASHI HIROTO , TOGASHI HITOSHI , TAKAHASHI TSUNEO
Published: March 2008

A 54‐year‐old woman who was being treated with 10 million units (mu) of natural interferon (IFN)‐α per day for chronic active hepatitis C at a local clinic, developed coma on the fourth day of treatment. On admission to Yamagata University Hospital, she was still in a state of semicoma with severe hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration of electrolytes, her condition improved remarkably. Endocrinological loading tests showed a hypofunction of the anterior pituitary gland. In consideration of these results, and her past experiences of haemorrhage during childbirth and subsequent amenorrhoea, we diagnosed her illness as a coma as a result of Sheehan's syndrome which had become overt during IFN therapy. She recovered completely after treatment with hydrocortisone and 1‐thyroxine.
Expression of P‐glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: Clinical correlation
Authors: CHOU YUH‐YU , CHENG ANN‐LII , HSU HEY‐CHI
Published: March 2008

Hepatocellular carcinoma (HCC), a chemoresistant tumour, is the most common fatal cancer in Taiwan. Hepatocellular carcinoma frequently expresses a high level of P‐glycoprotein (P‐gp), which is a specific phenotype of a multidrug‐resistance gene, and harbours mutations of the tumour suppressor gene p53. A modulatory relationship between p53 and P‐gp has been reported. In this study, we analysed the expression of P‐gp in relation to chemotherapeutic response and p53 protein expression in advanced HCC. Prechemotherapeutic tumour samples were obtained from 25 patients with HCC which had been treated with either etoposide (VP‐16) or doxorubicin. P‐glycoprotein and p53 in HCC were visualized by immunohistochemical staining using the monoclonal antibodies JSB‐1 and DO1, respectively. We investigated the correlation of P‐gp expression with chemotherapeutic responses, clinicopathological features and p53 protein expression. In our study, seven cases achieved partial remission, and the remaining 18 cases had a poor response to chemotherapy. Expression of P‐gp was observed in 13 tumours (52%). Positive P‐gp protein expression was significantly associated with non‐responders (8% or 1/13 vs 50% or 6/12, P= 0.03). Thus, P‐gp expression inversely correlated with chemotherapeutic response. Expression of p53 protein was seen in 12 cases and did not correlate with chemosensitivity or P‐gp expression. In summary, P‐gp expression correlates with the chemosensitivity of HCC that has been treated with VP‐16 or doxorubicin and p53 mutations do not appear to be a major determinant of P‐gp expression in advanced HCC.
Haemodynamic effects of chronic tetrandrine treatment in portal hypertensive rats
Authors: HUANG YI‐TSAU , CHENG YUH‐REN , LIN HAN‐CHIEH , CHEN CHIEH‐FU , HONG CHUANG‐YE
Published: March 2008

Tetrandrine is a calcium channel antagonist with reported antihypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed to investigate the haemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague‐Dawley rats. Animals were allocated into one of two groups: a tetrandrine group and a vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 h for 8 consecutive days, starting 1 day before ligation and continuing thereafter. After 8 days of tetrandrine treatment, systemic haemodynamics, organ blood flows and the degree of portal‐systemic shunting were measured after an overnight fast. The portal venous pressure and portal tributary blood flow were significantly decreased, while portal territory as well as hepato‐collateral vascular resistance significantly increased in the tetrandrine group compared with the vehicle group. The cardiac index was increased, while systemic vascular resistance was decreased, in the tetrandrine group. Mean arterial pressure, heart rate, portalsystemic shunting and bodyweight were similar between the two groups. Renal blood flow was decreased in the tetrandrine group. In conclusion, long‐term treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemia in portal hypertensive rats without affecting the portal‐systemic shunting.
Radiological retrospective study of gastric cancer in humans: Two patterns of development in elevated type gastric cancer
Authors: MIWA HIROTO , IWAZAKI RYOZO , OHKURA RYUICHI , NAGAHARA AKIHITO , MURAI TOSHIO , OGIHARA TATSUO , WATANABE SUMIO , SATO NOBUHIRO
Published: March 2008

A better understanding of the process of gastric cancer development would undoubtedly be helpful in diagnosis and treatment. However, there is little literature available concerning the natural history of elevated type gastric cancer in humans and this disease has not been systematically investigated. In this study the natural history of elevated type human gastric cancer was retrospectively investigated in 12 radiologically followed‐up patients. The cases were divided into two groups according to whether obvious abnormal findings were absent (group A, n= 5) or present (group B, n= 7) at initial examination. Clinico‐pathological features, including outcomes and DNA content of the tumours in both groups, were investigated and compared. Although the mean period between the initial and final examinations was significantly shorter in group A (19.6±11.7 months) than in group B (43.4±17.3 months), tumour size was significantly larger in group A (5.5±2.5 cm) than in group B (2.4±2.5 cm). Furthermore, group A showed deeper neoplastic cell invasion and worse outcomes. The DNA content of two cases in group A and four cases in group B was examined. One case in group A showed an aneuploid pattern, while all of those in group B showed a diploid pattern. These results indicate that the tumours in group A grew much faster than those in group B, which suggests the presence of two different patterns of development in elevated type gastric cancer.
Fas system and apoptosis in viral hepatitis
Authors: HAYASHI NORIO , MITA EIJI
Published: March 2008

Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the major causative agents of chronic liver disease. However, the mechanisms responsible for liver cell injury remain to be clarified. Playing crucial roles in the clearance of viral infection are cytotoxic T lymphocytes. Recently, it has been demonstrated that perforin‐ and Fas‐based mechanisms account for all T cell‐mediated cytotoxicity. Therefore, we examined the correlation between liver cell damage and the Fas system in the liver of patients with chronic hepatitis C. Fas is a cell surface protein that mediates apoptosis with treatment of the Fas ligand or the anti‐Fas antibody. To investigate the role of Fas in type C hepatitis, we examined the correlation between liver cell damage and Fas expression. Fas expression was found mainly in the cytoplasm of hepatocytes and these positive cells were found particularly among infiltrating lymphocytes. A high prevalence of Fas expression was shown in liver tissue with more severe inflammation. The Fas system‐mediated death signal requires the interaction of Fas ligand with Fas on target cells. We isolated a 1.9 kb cDNA clone for the human Fas ligand and examined the expression of the Fas ligand in liver‐infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The open reading frame encodes 281 amino acids. Next, we examined the expression of the Fas ligand in liver‐infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The amplified products (231 bp) derived from Fas ligand transcripts were detected in liver‐infiltrating mononuclear cells, whereas no signal was observed in liver tissues. In HCV infection, Fas expression in hepatocytes is up‐regulated in accordance with the severity of liver inflammation. When HCV‐specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that can transduce the apoptotic death signal to Fas‐bearing hepatocytes. Thus, the Fas system plays an important role in liver cell injury by HCV infection.
Recent developments in autoimmune liver diseases
Authors: MANNS MICHAEL P
Published: March 2008

Several diseases are regarded as autoimmune liver diseases. Apart from the cholestatic liver diseases, primary biliary cirrhosis, primary sclerosing cholangitis, these include autoimmune hepatitis, hepatitis as part of the autoimmune polyendocrine syndrome type 1 (APS‐1) and particular overlap syndromes such as autoimmune cholangitis (also called antimitochondrial antibody negative primary biliary cirrhosis [PBC]), overlap syndrome chronic active hepatitis (CAH)/PBC and the overlap syndrome primary sclerosing hepatitis (PSC)/CAH. In addition, auto‐antibodies may be observed during the course of chronic viral hepatitis, in particular chronic hepatitis C and D. Finally, a small number of drug‐induced liver diseases is immune mediated. The following article will review our recent progress in the field of autoimmune hepatitis including APS‐1 and autoimmunity in viral hepatitis and immune‐mediated drug‐induced liver disease.
Living related donor liver transplantation
Authors: CHEN CHAO‐LONG , CHEN YAW‐SEN , LIU PO‐PING , CHIANG YUAN‐CHENG , CHENG YU‐FAN , HUANG TUNG‐LIANG , ENG HOCK‐LIEW
Published: March 2008

Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra‐operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra‐operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n= 10) and glycogen storage disease (n= 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.
Case Report: Congenital absence of the portal vein associated with nodular hyperplasia in the liver
Authors: MOTOORI SHIGEATSU , SHINOZAKI MASAMI , GOTO NOBUAKI , KONDO FUKUO
Published: March 2008

Congenital absence of the terminal portion of the portal vein with visceral venous return to the suprahepatic inferior vena cava, a rare malformation, was demonstrated in an 18‐year‐old Japanese woman. She had nodular hyperplasia in the liver and a non‐functioning pancreatic endocrine tumour. It is generally believed that reduction of portal venous flow causes atrophic changes and, subsequently, nodular hyperplasia occurs in a well‐perfused area in the liver. However, the liver was not perfused by the portal vein in this case. It is suggested that nodular hyperplasia can occur without portal blood flow.
Serum levels of sCD23, interleukin‐10 and interferon‐γ in patients with coeliac disease
Authors: BANSAL AS , BRUCE J , THOMSON A , KERLIN P
Published: March 2008

The role of cellular and humoral immunity coeliac disease was investigated by the measurement of serum levels of interleukin‐10 (IL‐10), interferon‐gamma (IFN‐γ) and soluble CD23 (sCD23). Coeliac disease was diagnosed by duodenal biopsy and response to a gluten‐free diet (GFD). The results were compared with age and sex‐matched patients with non‐specific upper gastrointestinal symptoms and normal duodenal histology. While the levels of serum IL‐10 were significantly elevated (P < 0.01) in patients with coeliac disease taken as a whole, the levels of serum IFN‐γ were normal and sCD23 significantly decreased (P < 0.002). The median serum sCD23 was significantly lower in the coeliac disease patients not on a GFD compared with those asymptomatic on a GFD (P < 0.03) and the control group (P < 0.0004). The coeliac disease patients on a GFD also had significantly lower serum sCD23 and higher IL‐10 compared with the control group (P < 0.01 and P < 0.015). There was no significant difference in the serum IL‐10 between the coeliac disease patients on a GFD and those not on a GFD and between the latter and the control group. The low levels of serum sCD23 in coeliac disease suggest diminished humoral immunity and, conversely, exaggerated cellular immunity. The aetiology of the raised levels of IL‐10 in coeliac disease is unclear and similar to that observed in patients with inflammatory bowel disease. However, this may represent a regulatory response to the elevated levels of proinflammatory cytokines described in coeliac disease. A combination of diminished sCD23 and raised IL‐10 is clearly unusual as both are associated with Th2‐type functions. The possible causes of this finding are discussed.
Hepatitis viruses under immunosuppressive agents
Authors: LIAW YUN‐FAN
Published: March 2008

Clinical and experimental studies have shown that T cell‐mediated immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV) and hepatitis C virus infection. Immunosuppressants may impair T cell function and thereby reduce immune‐mediated hepatocytolysis and virus clearance. In addition, corticosteroid may activate the glucocorticoid responsive element in the HBV genome to enhance HBV replication and gene expression. These combined effects result in an increase of viraemia in association with a decrease of serum aminotransferase and hepatic necroinflammation. In acute infection, use of immunosuppressants will increase the incidence of chronic evolution. In chronic infection, withdrawal of immunosuppressants will be followed by a clinical flare due to a rebound of immune attack to hepatocytes with increased viral load. This may lead to a subsequent decrease of the viraemia. Therefore, short‐term use of immunosuppressant before antiviral therapy may be beneficial in the treatment of chronic viral hepatitis. However, the clinical rebound may be extremely severe and lead to hepatitis failure; thus, the patients should be monitored closely upon tapering and after the withdrawal of immunosuppressants. Long‐term use of immunosuppressants in patients with hepatitis virus infection is usually deleterious, particularly in patients after organ transplantation. These findings suggest that clinicians should be cautious in the use of immunosuppressants in patients with hepatitis virus infection.
Combined hepatocellular‐cholangiocarcinoma: A clinicopathological study
Authors: NG IRENE OL , SHEK TONY WH , NICHOLLS JOHN , MA LILY T
Published: March 2008

Combined hepatocellular‐cholangiocarcinoma (HCC‐CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16–79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n= 18) of tumours were ‘mixed’ tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a ‘fibrolamellar’ tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin‐producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin‐negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum α‐fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC‐CC were short. In conclusion, HCC‐CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.
Intra‐arterial carbon dioxide‐enhanced ultrasonogram of hepatocellular carcinoma treated by transcatheter arterial embolization and percutaneous ethanol injection therapy
Authors: CHEN RAN‐CHOU , WANG CHUNG‐KWE , CHIANG LIANG‐CHUNG , LO HSIN‐YEN , DUH SHGI‐JYE , CHEN WEI‐TZUNG , TU HSING‐YANG , LIAO LI‐YING , WANG CHAUR‐SHINE , CHEN PAO‐HUEI
Published: March 2008

The purpose of this study was to investigate the value of carbon dioxide‐enhanced ultrasonography (CO2‐US) in the evaluation of viable hepatocellular carcinomas (HCC) which were treated by transcatheter arterial embolization (TAE), percutaneous ethanol injection (PEI), or a combination treatment (TAE and PEI). Forty‐one patients with 66 HCC were included in the study. They underwent CO2‐US and angiography were performed in all tumours after they were treated by TAE, PEI or a combination treatment. Forty‐six tumours were positively enhanced by CO2‐US and 40 of them were positive by angiography. These 46 tumours were proved to be viable tumours either by biopsy or by follow‐up studies. The positive predictive value was 100% for CO2‐US and 87.8% in angiography. Twenty tumours were negative by CO2‐US and these were also negative by angiography. Carbon dioxide‐enhanced ultrasonography is a more reliable method for detecting the viable portion of the treated HCC compared with conventional angiography.
Changes in biliary excretory mechanisms in rats with ethinyloestradiol‐induced cholestasis
Authors: TAKIKAWA HAJIME , TAKAMORI YORIYUKI , SANO NAOYO , KUYAMA YASUSHI , YAMANAKA MASAMI
Published: March 2008

Several excretory pathways for cholephilic compounds have been known. To examine the changes in excretory pathways in cholestasis induced by ethinyloestradiol, various bile acids, organic anions and organic cations were intravenously administered to ethinyloestradiol‐treated rats and their biliary excretion was studied. Biliary excretion of taurocholate was slightly delayed, but its excretory maximum was markedly decreased. Biliary excretion of lithocholate‐3‐O‐glucuronide, leukotriene C4, sulphobromophthalein and pravastatin was markedly impaired to a similar extent. Biliary excretion of vinblastine, a P‐glycoprotein substrate, was increased, suggesting increased expression of P‐glycoprotein. In contrast, biliary excretion of erythromycin, a cationic antibiotic, was markedly impaired. In conclusion, ethinyloestradiol treatment altered the biliary excretion of organic compounds, which may partly be related to changes of the canalicular transporters.
Acute in vivo effect of octreotide acetate, a somatostatin analogue on the cellular function of gastric mucosa in the rat
Authors: MOTEGI MASAHIKO , NAGAMACHI YUKIO , KANEKO TETSUYA , MATSUZAKI SHIGERU
Published: March 2008

Somatostatin is known to suppress various cellular functions of the gastrointestinal tract. In the present study, octreotide acetate, a synthetic long‐acting somatostatin analogue was tested for its effects on some cellular functions of gastric mucosa. Octreotide raised the gastric mucosal pH within 1 h after a single subcutaneous injection to rats at doses of 1–100 μg/kg bodyweight. Serum gastrin levels increased transiently at a dose of 10 μg/kg bodyweight but not at 100 μg/kg. Basal levels of serum gastrin were not affected, while famotidine‐induced gastrin secretion was suppressed by octreotide at a single dose of 100 μg/kg. The increase in the intragastric acidity and histidine decarboxylase activity following pentagastrin treatment was significantly reduced by octreotide. These results suggested that this somatostatin analogue inhibits the function of not only the parietal cell and G cell but also the enterochro‐maffin‐like (ECL) cell, resulting in intraluminal hypoacidity.
Oral human spasmolytic polypeptide protects against aspirininduced gastric injury in rats
Authors: COOK GREGORY A , THIM LARS , YEOMANS NEVILLE D , GIRAUD ANDREW S
Published: March 2008

Spasmolytic polypeptide (SP) is a member of the trefoil peptide family; gut peptides that participate in the protection and repair of the gastric mucosa. Previous studies have failed to agree on the mode of action of human SP (hSP). We investigated the effect of orally administered human SP on the protection and repair of rat gastric mucosa in an established in vivo model of damage induced by the non‐steroidal anti‐inflammatory drug aspirin (ASA). The integrity of the gastric mucosa was quantified in four ways: the temporal change in transmucosal potential difference (PD), area of macroscopic damage by planimetry, relative area of microscopic damage by histological morphometry, and the number of deep erosions per centimetre of mucosa sectioned. Human SP (200 μmol/L) administered orally before, or in combination with ASA significantly reduced the fall in PD, the area of microscopic damage, and the number of deep erosions (P < 0.05). The area of macroscopic damage was significantly reduced only in rats where hSP (200 μmol/L) was given in conjunction with ASA (P < 0.05). Human spasmolytic polypeptide (70 or 200 μmol/L) administered after ASA failed to hasten the re‐establishment of PD or stimulate the repair of the gastric mucosa in the 90 min following injury (P>0.05, compared with ASA alone). We conclude that hSP prevents gastric mucosal damage by its topical actions, probably by a rapid interaction with luminal mucins or epithelial cells, but fails to stimulate early restitution in the injured gastric mucosa.
Greatly increased mucosal nitric oxide in ulcerative colitis determined in situ by a novel nitric oxide‐selective microelectrode
Authors: IWASHITA ETSURO
Published: March 2008

Although current nitric oxide (NO) electrodes are simple, selective and sensitive, they are fragile and hard to use in clinical studies of patients. By preparing an improved NO electroneedle that overcomes these defects, we directly measured mucosal NO concentrations in 11 patients (six male, five female; mean 26.0 years old) with ulcerative colitis (UC) and five normal volunteers (three male, two female; mean 28.3 years old) in situ. An electroneedle was inserted into colonic mucosa through a biopsy channel during colonoscopy. The information concerning the concentration of NO generated and the appearances of the colonic mucosa at the same site were obtained simultaneously. In the ulcerative colitis patients, NO concentrations were significantly increased at all 24 mucosal sites tested. These included sites where: there was an absence of visible inflammation (five sites); the mucosa was mildly inflamed (eight sites); the mucosa was moderately inflamed (five sites); or severely inflamed (six sites). The NO concentrations in ulcerative colitis patients were 12–72 times higher than the NO levels in normal controls (10 sites). At the same 10 sites in four ulcerative colitis patients, the high NO concentrations were decreased by 53% after glucocorticoid treatment. These data are consistent with those of previous studies utilizing different NO electrodes. Excess mucosal NO is generated from inducible NO synthase in the inflamed mucosa itself and the invading inflammatory cells. Our results suggested that mucosal NO could be a marker for the extent of inflammation and its various actions correlated with the pathogenesis, natural history and prognosis of UC. Using the NO microelectrode system reported here, the concentration of NO generated can be monitored in real‐time while observing the mucosal condition at the same site during endoscopy. This novel NO electrode may contribute to understanding the role of NO in colonic mucosal inflammation.
CASE REPORT: An inherited APC mutation in the first reported Australian case of Turcot's syndrome
Authors: TOMARAS CONSTANTINE , PAINTER DOROTHY M , BASHA NUR J , KOOREY DAVID J
Published: March 2008

The objective of this study was to determine the inherited gene mutation responsible for the first reported Australian case of Turcot's syndrome. DNA was extracted from the archival tissue blocks obtained at the time of the patient's original surgery and from fresh blood samples obtained from selected family members. These were analysed for mutations of the familial adenomatous polyposis gene (APC). Analysis of DNA from the archival blocks and from each of the affected family members revealed an inherited 5 base pair deletion at codon 1061 of APC. In this case, the central nervous system tumour represents an extracolonic manifestation of familial adenomatous polyposis. The underlying inherited mutation of APC has been identified. In some cases of Turcot's syndrome, other genes appear to be involved. Recent literature examining the molecular basis of Turcot's syndrome is reviewed.