bluuebunny/crossref_metadata_2025 huggingface dataset:
REVIEW: Hepatitis delta
Authors: HADZIYANNIS STEPHANOS J
Published: March 2008

The causative agent of hepatitis delta virus (HDV) is the most unusual of all causative agents for all hepatitis viruses. Current knowledge of the molecular biology of HDV strengthens its proposed classification within the satellites, a family of subviral agents, some of which are pathogens of higher plants. Hepatitis delta virus is the only virus in the satellite family known to infect animal species, with hepatitis D having affected more than 10 million people worldwide who are also infected with its helper virus, HBV. Recently, the world map for hepatitis D appears somewhat modified, with decreasing HDV prevalence in certain areas and some new foci of HDV endemicity. Despite changing HDV prevalence, hepatitis D, particularly the chronic form, is still an important health problem worldwide in terms of morbidity and mortality (mainly due to chronic liver disease, including hepatocellular carcinoma). Molecular studies have greatly advanced our understanding of the life cycle of HDV and of the function of its proteins. The new molecular information is of clinical relevance, with implications for the pathogenesis of liver damage, the diagnosis of HDV infection, for the natural course of the disease and, potentially, for therapy. Sensitive assays for HDV‐RNA by polymerase chain reaction and sequencing techniques have clarified the patterns of HDV transmission and have confirmed the existence of unusual clinical forms of the virus and their relationship to replicative levels and genotypes of HDV. Prevention and treatment of hepatitis D are still in their infancy. However, liver transplantation for delta cirrhosis has proven far more successful than in any other viral form of cirrhosis, with few reinfections of the grafted liver, and has given important information on HDV biology and the pathogenesis of liver damage.
Dimethylsulfoxide maintains intercellular communication by preserving the gap junctional protein connexin32 in primary cultured hepatocyte doublets from rats
Authors: YOSHIZAWA TAKASHI , WATANABE SUMIO , HIROSE MIYOKO , MIYAZAKI AKIHISA , SATO NOBUHIRO
Published: March 2008

Intercellular communication via gap junctions is one of the differentiated functions of cells. Dimethylsulfoxide (DMSO) is known to induce cell differentiation and maintain differentiated cellular functions in primary hepatocyte culture, but the mechanism of action of DMSO is unknown. Therefore, we investigated the effect of DMSO on cell‐cell communication via gap junctions of hepatocyte doublets, which are differentiated cells that lose differentiated functions with time in culture. In isolated rat hepatocyte doublets, we assessed the effects of 1, 2 and 3% DMSO in culture medium on morphological changes and dye‐coupling activity between pairs of cells by microinjection with fluorescent dye (Lucifer Yellow CH). The distribution of gap junction protein connexin32 (Cx32) was assessed by indirect immunofluorescence analysis and the Cx32 mRNA was detected by the reverse transcription‐polymerase chain reaction method. Dimethylsulfoxide delayed the morphological change of hepatocyte doublets from a spherical to a flattened shape. Dye‐coupling efficiency significantly decreased with time in culture in the control group, whereas in groups treated with 2 and 3% DMSO, dye‐coupling efficiency was retained after 6 and 9 h of inoculation (P < 0.05 and P < 0.01, respectively). Analysis by indirect immunofluorescence showed few fluorescent spots for Cx32 in the control group at 9 h of incubation, whereas many punctate fluorescent spots were seen in the 3% DMSO group at 9 h of incubation. The detection of Cx32 mRNA in the 3% DMSO group was also stronger than in controls. Dimethylsulfoxide significantly maintained intercellular communication via gap junctions in primary cultured rat hepatocytes through the preservation of functional Cx32 protein, thus maintaining cell differentiation.
Therapeutic results of endoscopic variceal ligation for acute bleeding of oesophageal and gastric varices
Authors: HARADA TOSHIYA , YOSHIDA TOMOHARU , SHIGEMITSU TOSHINORI , TAKEO YOSHIFUMI , TADA MASAHIRO , OKITA KIWAMU
Published: March 2008

Endoscopic variceal ligation (EVL) using ‘O’ rings is widely accepted as a treatment of oesophageal varices that is at least as effective as endoscopic injection sclerotherapy but which produces fewer complications. Endoscopic variceal ligation using detachable snares has attracted attention as a safe and easy method of endoscopic treatment for gastric varices. Nineteen patients with acute bleeding from oesophageal or gastric varices were treated in the present study. Of these, 14 patients were treated with EVL using ‘O’ rings and five patients were treated with EVL using detachable snares and the treatment results were evaluated. Haemostasis was achieved in all patients. No serious complications of the procedures were observed. However, recurrences and rebleeding were observed in some patients during the maximum follow‐up period of 24 months. Endoscopic variceal ligation using ‘O’ rings and detachable snares is useful for achieving haemostasis in cases of acute bleeding from oesophageal or gastric varices. However, additional endoscopic sclerotherapy may be needed to eliminate the variceal feeding vessels to further improve the long‐term prognosis of these patients.
CASE REPORT: Life‐threatening haematochezia from a jejunal leiomyoma
Authors: CHEN CHIH‐YEN , LU CHING‐LIANG , LO SU‐SHUN , YU I‐TING , CHANG FULL‐YOUNG , LEE SHOU‐DONG
Published: March 2008

Leiomyoma is a common benign intestinal tumour. Melaena is not rare in this tumour. Recently, rectal haematochezia has been considered as one of the very rare manifestations of leiomyoma. We report a case of jejunal leiomyoma showing life‐threatening rectal bleeding. This 76‐year‐old man was admitted to hospital because of continuous rectal bleeding for 2 days. Haemorrhagic shock occurred and transfusion of 27 units of packed red blood cells failed to correct the shock. Emergent superior mesenteric angiography revealed a distal jejunal tumour showing evidence of active oozing. Segmental intestinal resection was performed to remove this jejunal tumour. Final pathological examination disclosed a jejunal leiomyoma with a ruptured artery responsible for the life‐threatening bleeding. The patient recovered after tumour resection. Our presenting case was probably the second case of jejunal leiomyoma showing haematochezia. The diagnostic priority is discussed.
Gall‐bladder wall thickening in patients with liver cirrhosis
Authors: WANG TEH‐FANG , HWANG SHINN‐JANG , LEE FA‐YAUH , TSAI YANG‐TE , LIN HAN‐CHIEH , LI CHUNG‐PIN , CHENG HUEI‐MIN , LIU HAW‐JANG , WANG SUN‐SANG , LEE SHOU‐DONG
Published: March 2008

Gall‐bladder wall thickening is commonly seen in patients with cirrhosis, but its exact causes have not been well established. We evaluated clinical, biochemical and haemodynamic data of patients with cirrhosis with respect to the presence of thickening of the gall‐bladder wall. After excluding patients who presented with gallstones, acute or chronic cholecystitis, heart failure, a serum creatinine level greater than 2 mg/dL and/or a serum alanine aminotransferase level greater than 400 U/L, 77 patients with cirrhosis (75 male, two female; mean age 58±8 years) were enrolled in the study. Clinical, biochemical, ultrasound and haemodynamic data were obtained in every patient. Fortyone (53%) of 77 patients with cirrhosis had gall‐bladder wall thickening (>4mm). Compared with patients with a normal gall‐bladder wall, patients with gall‐bladder wall thickening had significantly lower serum albumin levels (3.6±0.6 vs 2.9±0.7 gm/dL, respectively; P< 0.05), a longer prothrombin time (13±6 vs 16±6s, respectively; P<0.05), more patients with Child‐Pugh class C (6 vs 37%, respectively; P<0.05) and more patients with ascites (8 vs 50%, respectively; P<0.05). In addition, compared with patients with a normal gall‐bladder wall, those patients with gall‐bladder wall thickening had a higher hepatic venous pressure gradient (13.9±4.5 vs 17.1±4.1 mmHg, respectively; P<0.01) and a lower systemic vascular resistance (SVR; 1144±332 vs 1010±318 dyn.s/cm5, respectively; P< 0.05). Using a multivariate analysis, the presence of ascites and SVR lower than 900 dyn.s/cm5, were independently correlated with the presence of gall‐bladder wall thickening, while a hepatic vein pressure gradient greater than 10 mmHg had only a marginally significant association. The presence of ascites, decreased SVR and portal hypertension are related to the occurrence of gall‐bladder wall thickening in patients with cirrhosis, indicating that the development of gall‐bladder wall thickening may be multifactorial.
Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C
Authors: HWANG SHINN‐JANG , LEE SHOU‐DONG , LI CHUNG‐PIN , LU REI‐HWA , CHAN CHO‐YU , WU JAW‐CHING
Published: March 2008

Cryoglobulinaemia is the most common immunological disorders seen in patients with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this phenomenon were also evaluated. Fifty‐four (44%) of the 122 patients with chronic hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia, neuropathy and renal involvement. The patients with cryoglobulinaemia were predominantly female and had a significantly higher mean serum level of rheumatoid factor and a lower mean serum C4 level compared with patients without cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P < 0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto‐antibodies, and the rate of cirrhosis were not significantly different between the two groups. Univariate logistic regression analysis showed female serum levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL), C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis showed only serum C4 levels (< 20 mg/dL) as a significantly independent predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis C patients with cryoglobulinaemia and the serum C4 level was the only clinical independent predictor associated with this phenomenon. Hepatitis C virus genotype and serum viral load were not clinical independent predictors.
Natural history of chronic hepatitis B virus infection: An immunopathological study
Authors: CHU CHIA‐MING , LIAW YUN‐FAN
Published: March 2008

Three clinicopathological phases of chronic hepatitis B virus (HBV) infection are identified. First, is immune tolerance of HBV. High levels of viraemia are associated with normal alanine aminotransferase (ALT) levels and minimal histological lesions. More than 30–40% of hepatocytes have the hepatitis B core antigen (HBcAg), predominantly in their nuclei. Maternally derived hepatitis B e antigen (HBeAg) crossing the placenta may result in the elimination of T helper cells responsive to HBeAg/HBcAg. This phase can last for periods ranging from a few weeks to 10 or more years until the immune tolerance is lost. Second, is the immune clearance of HBV. Intermediate levels of viraemia are associated with fluctuating ALT levels and active and ongoing hepatitis. Approximately 20–30% of hepatocytes have HBcAg, predominantly in their cytoplasm. Expression of pre‐core defective HBV mutants during chronic HBV infection may lead to a reduction in the secretion of HBeAg and may trigger the beginning of the immuno‐elimination phase. The mechanism of intrahepatic shift of HBcAg from the nucleus to the cytoplasm and the decreased levels of viraemia in this phase may be, at least in part, secondary to liver damage and regeneration. Third, is latent infection with residual integrated HBV. Undetectable viraemia is associated with normal ALT levels and no virus‐induced liver damage. With regard to hepatocyte expression of HBsAg in chronic HBV infection, membrane staining of HBsAg on hepatocytes has been shown to correlate well with the presence of viraemia. The degree of cytoplasmic hepatitis B surface antigen (HBsAg) expression inversely correlates with the level of viraemia. Therefore, HBsAg carriers with high levels of viraemia have low levels of cytoplasmic hepatitis B surface antigen (HBsAg) expression, while those with low levels of viraemia have high levels of cytoplasmic HBsAg expression. However, several exceptions have been identified. High levels of viraemia associated with high levels of cytoplasmic HBsAg expression were recognized in patients with fibrosing cholestatic hepatitis. In contrast, low levels of viraemia associated with low levels of cytoplasmic HBsAg expression were recognized in patients with hepatitis C virus but not hepatitis D virus superinfection.
Hepatitis in patients with end‐stage renal disease
Authors: HUANG CHIU‐CHING
Published: March 2008

Hepatitis B and hepatitis C are two common pathogens causing chronic hepatitis in patients with end‐stage renal disease (ESRD). With the acceptance of hepatitis B s antigen (HBsAg) screening, infected patients have been identified and isolated over the past 20 years. Consequently, hepatitis B is now being seen less frequently in dialysis units. Even though hepatitis B has become less of a problem, non‐A, non‐B hepatitis has been recognized as a sigmlicant problem since 1979. With the availability of serological testing for hepatitis C virus (HCV), more specific information is now available in regard to HCV infection in dialysis patients. The prevalence of anti‐HCV in haemodialysis (HD) patients is quite variable, ranging from 5 to over 50%. Anti‐HCV positivity is associated with previous blood transfusions, mode of therapy and duration of haemodialysis. In Spain and Italy, the annual seroconversion rates of HCV antibodies in dialysis patients are 2–9%; this rate was much higher in Taiwan (15%). Whether patients with HCV infection should be identified and isolated during HD treatment is an issue of controversy. Transplantation is associated with increases in hepatitis B virus (HBV) replicative markers. The survival disadvantage in HBsAg‐positive recipients usually did not become apparent until 8 years after transplantation. Hepatitis C virus‐infected renal transplant recipients are presumably in a similar situation to patients with hepatitis B, although confirmatory data are currently lacking. Coinfection of HBV and HCV may lead to aggressive liver disease and cirrhosis. A hepatitis B vaccine is recommended for all susceptible dialysis patients. Dialysis patients have lower response rates to hepatius B vaccines than do other people. Currently, no vaccine is available for hepatitis C. To date, there are no effective treatments available for hepatitis B and hepatitis C. Combination therapy with interferodlamivudine for hepatitis B and interferodribavirin for hepatitis C may offer a promise of effective control of viral replication in the future.
Drug‐induced hepatic injury
Authors: FARRELL GEOFFREY C
Published: March 2008

Drugs and other chemical toxins account for less than 5% of cases of jaundice or acute hepatitis and fewer cases of chronic liver disease, but they are an important cause of more severe types of hepatic injury. Drug reactions produce an array of hepatic lesions that mimic all known hepatobiliary diseases; this poses a diagnostic challenge for physicians and pathologists. Diagnosis of drug‐induced hepatic injury is circumstantial, with positive rechallenge being the only factor that unequivocally implicates a particular agent. Nonetheless, other aspects of the temporal relationship between drug ingestion and adverse reaction, exclusion of other diseases, the presence of extrahepatic features of drug hypersensitivity and some findings on liver biopsy can lend support to the diagnosis. Some of these issues will be explored in this review by considering contemporary paradigms of drug‐induced hepatic injury. Factors that predispose to dose‐dependent hepatic injury will be considered in relation to acetaminophen, an example of acute hepatotoxicity, and methotrexate, an agent that can produce hepatic fibrosis. Flucloxacillin will be discussed as an example of drug‐induced cholestatic hepatitis often associated with prolonged cholestasis and the vanishing bile duct syndrome. Minocycline and diclofenac will be mentioned as two drugs for which drug hepatitis is an exceedingly rare complication. Finally, the evidence that Chinese herbal medicines can be hepatotoxic will be reviewed.
Review: Molecular approaches to inherited liver disease. Focus on Wilson disease
Authors: COX DIANE W
Published: March 2008

Although infectious agents account for a large proportion of liver disease, inherited forms of liver disease, often treatable, must not be overlooked. New approaches to the cloning of disease genes are allowing an increased understanding of the basic defect of human diseases. Identification of disease genes can have practical applications for diagnosis, can provide information on prognosis and can lead to new therapies. This review focuses on selected inherited liver diseases and the knowledge to be gained from molecular studies. Three genetic diseases affecting the liver, Wilson disease, haemochromatosis and α1‐antitrypsin deficiency, are selected as examples of current approaches to the study of genetic liver disease.
Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress
Authors: ISHII HIROMASA , KUROSE IWAO , KATO SHINZO
Published: March 2008

Oxidative stress is well recognized to be a key step in the pathogenesis of ethanol‐associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen reactive species and/or by decreasing the level of endogenous antioxidants. Numerous experimental studies have emphasized the role of the ethanol‐inducible cytochrome P450 in the microsomes and the molybdo‐flavoenzyme xanthine oxidase in the cytosol. This review shows the putative role of ethanol‐induced disturbances in iron metabolism in relation to iron as a pro‐oxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Many previous studies suggest a role for active oxygens in ethanol‐induced mitochondrial dysfunction in hepatocytes. Recent studies in our laboratory in the Department of Internal Medicine, Keio University, using a confocal laser scanning microscopic system strongly suggest that active oxidants generated during ethanol metabolism produce mitochondrial membrane permeability transition in isolated and cultured hepatocytes. In addition, acetaldehyde, ethanol consumption‐associated endotoxaemia and subsequent release of inflammatory mediators may cause hepatocyte injury via both oxyradical‐dependent and ‐independent mechanisms. These cytotoxic processes may lead to lethal hepatocyte injury. Investigations further implicate the endogenous glutathione—glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocytes exposed to ethanol.
Non‐surgical treatment of hepatocellular carcinoma
Authors: LIN DENG‐YN , LIN SHI‐MING , LIAW YUN‐FAN
Published: March 2008

A decade ago, surgery was the only satisfactory treatment modality for hepatocellular carcinoma (HCC), but it was limited only to selected cases. For the majority of cases of HCC, systemic chemotherapy was one of the few treatment alternatives, but provided only marginal benefit. In the past 20 years, diagnostic methods have improved to an extent that small HCC less than 1 cm can be detected. Moreover, non‐surgical treatment is available, of which regional therapy has been shown to prolong patients’ survival, and may even replace surgical resection in some cases. Regional therapy is indicated for the treatment of HCC when there is no extrahepatic metastasis and the patient has adequate liver function reserve, thus permitting repeated therapy. Transcatheter hepatic arterial embolization (TAE) using various embolizers has been well documented to include controlled studies. However, it is not indicated for patients with thrombosed main portal veins. Its therapeutic effect is also doubtful when the tumour is infiltrative in nature or is hypovascular, too large or too small. Additional chemotherapeutic agents mixed into the embolizer with lipiodol and degraded starch microspheres or styrene‐maleic acid‐neocarzinostatin in which chemotherapeutic agents are embedded, are used with a better response, but the survival rate has not shown significant improvement. Ultrasound‐guided local injection therapy is another new method of treatment of HCC. Of these techniques, percutaneous ethanol injection therapy (PEIT) is widely used with excellent results for small, encapsulated tumours in livers with less than three HCC. Percutaneous ethanol injection therapy can also be used in cases with portal vein thrombosis, but it is not suitable for patients having coagulopathy or ascites. Using acetic acid, OK‐432, interferon or anti‐cancer drugs in the injection therapy shows no further benefit over ethanol alone. Transcatheter echoguided thermotherapy or cryotherapy has been reported in small series of patients, as has target therapy with immune or radiotherapy and conformal radiotherapy. Preliminary studies show encouraging results. Systemic therapy with either single drug or multidrugs is ineffective, with a response rate of less than 20%. Immunotherapy, such as with interferon or other cytokines, is not beneficial. Hormone therapy has not been promising, except for treatment with tamoxifen, which has been reported to show some beneficial effect. Gene therapy is still in its infancy. In summary, recent progress in non‐surgical treatment of HCC has resulted in a breakthrough of regional therapy looking quite promising. Moreover, a combination of different types of regional therapies may yield better outcomes in selected individuals.
Distribution of hepatitis C virus genotypes among blood donors in Taiwan
Authors: WU CHII H , LEE MEY F , KUO HSIEN S
Published: March 2008

The aim of this study was to investigate the prevalence and distribution of hepatitis C virus (HCV) genotypes of blood donors in Taiwan. RNA was extracted from the serum of anti‐hepatitis C virus‐positive carriers and this was followed by reverse transcriptase—polymerase chain reaction (RT‐PCR) using type‐specific primers for the presence of HCV genotypes, 1a, 1b, 2a, 2b, 3a and 6a. Of the 604 anti‐HCV‐positive specimens, the PCR demonstrated that 93.0% (562/604) were positive for at least one HCV genotype. The remaining 42 specimens (7%) were HCV negative. Among the 562 HCV‐positive specimens, 505 (89.8%) contained HCV 1a, 1b, 2a, 2b and 3a as the only genotype, with a prevalence of 0.4% (2/562), 60.1% (338/562), 15.5% (87/562), 11.9% (67/562), and 2.0% (11/562), respectively. No HCV genotype 6a was found. Thirty‐seven specimens (6.6%) exhibited mixed infections with multiple HCV genotypes that included types 1b, 2a and 2b, while 20 (3.5%) HCV RNA‐positive sera remained unclassified. These results confirm that the predominant HCV genotype in Taiwan is 1b. In addition, genotypes 1a and 3a can also be found in Taiwan at low frequency.
Diagnostic value of anti‐hepatitis D virus (HDV) antibodies revisited: A study of total and IgM anti‐HDV compared with detection of HDV‐RNA by polymerase chain reaction
Authors: HUANG YI‐HSIANG , WU JAW‐CHING , SHENG WEN‐YUNG , HUO TEH‐IA , CHANG FULL‐YOUNG , LEE SHOU‐DONG
Published: March 2008

A high serum titre (≥ 1000 or ≥ 5000) of total antibody to hepatitis D virus (anti‐HDV) and positive for immunoglobulin (Ig) M anti‐HDV have been used to represent HDV replication, while reverse transcription‐polymerase chain reaction (RT‐PCR) is currently the most sensitive assay for detecting HDV viraemia. The aim of the present study was to re‐evaluate the correlation of total anti‐HDV and IgM anti‐HDV with HDV viraemia based on RT‐PCR and to assess the clinical significance of these markers in acute and chronic HDV superinfection. Chronic HDV infection was defined as positive HDV‐RNA by RT‐PCR for more than 6 months, while total anti‐HDV titre was defined by serial dilution. Of 178 hepatitis B virus (HBV) carrier patients studied, 119 cases had been anti‐HDV positive for more than 6 months. Two‐thirds (79/119) were positive for HDV viraemia by RT‐PCR. Only half the chronic HDV viraemic patients had a high titre (≥ 1000) of total anti‐HDV, and there was only moderate agreement (K = 0.41) between total anti‐HDV titre/IgM anti‐HDV and HDV‐RNA and chronic HDV viraemia. Based on cross‐sectional and longitudinal follow‐up analyses, serum total anti‐HDV titres ≥ 100 appeared to be an excellent cut‐off titre (K = 0.91) in differentiating chronic from acute HDV infection among viraemic patients. In summary, IgM and a high titre total of anti‐HDV are not good markers of HDV viraemia, but an anti‐HDV titre of ≥ 100 appears to be an excellent marker for the differentiation of acute from chronic HDV superinfection.
Acute hepatitis C among renal failure patients on chronic haemodialysis
Authors: OKUDA KUNIO , HAYASHI HARUYUKI , YOKOZEKI KAZUO , KOBAYASHI SUSUMU , KASHIMA TAKASHI , IRIE YASUBUMI
Published: March 2008

Hepatitis C virus (HCV) infection is common in haemodialysis units, yet little information is available about the clinical feature of acute hepatitis C among renal failure patients. The present study is based on 49 cases of acute hepatitis C seen at a haemodialysis centre where sporadic nosocomial infection was occurring up to June 1993. Liver function tests were done at 4 weekly intervals on all dialysis patients, anti‐HCV antibodies were tested by the C‐100 and second generation tests and serum HCV‐RNA was determined by the branched DNA and Amplicore tests. Diagnosis of acute hepatitis C was made on the basis of an acute rise in alanine aminotransferase (ALT) and seroconversion to positive anti‐HCV antibodies. Clinical presentation of acute hepatitis was generally mild with rare overt jaundice and the diagnosis was possible only from increased ALT, which was generally low. Spontaneous resolution of acute hepatitis within 8 months with clearance of viral RNA occurred in only four cases, 91.8% of patients developing chronic hepatitis. Biopsy in 12 cases with high ALT levels showed mild to moderate inflammatory activities. In conclusion, the clinical presentation of acute hepatitis C is generally mild in chronic haemodialysis patients, but spontaneous resolution is infrequent. A longer follow‐up period is required for defining the long‐term prognosis.
Computer morphometry for quantitative measurement of liver fibrosis: Comparison with Knodell's score, colorimetry and conventional description reports*
Authors: LIN XI‐ZHANG , HORNG MING‐HWUI , SUN YUNG‐NIEN , SHIESH SHU‐CHU , CHOW NAN‐HAW , GUO XIOU‐ZHEN
Published: March 2008

Liver fibrosis is currently described quite subjectively or, at best, semiquantitatively by scoring systems. In order to measure the severity of liver fibrosis quantitatively and to compare this with established methods, such as Knodell's scoring system, the colorimetric method and conventional description reports, we undertook the present study. A personal computer with an image grabber card and a microscope equipped with a computer‐controlled slide‐driver was used for computer morphometry. The principle behind morphometry is based on the different colours of hepatocytes and fibres following staining with Masson's trichrome stain. There were 31 patients (25 male, six female) recruited into the present study with a mean ±SD age of 41.6 ± 15 years (range 24–66 years). Of these patients, 16 had chronic hepatitis B, 12 had chronic hepatitis C and three were alcoholics. Colorimetric methods and Knodell's fibrosis score were performed according to established protocols. Conventional description reports were obtained from reviews of patient charts. The results from computer morphometry were highly correlated with results from the colorimetric method, with a correlation coefficiency γ= 0.85 (P < 0.0001). The results from computer morphometry also correlated with both Knodell's scoring system (γ= 0.69; P < 0.001) and conventional description reports (γ= 0.46; P < 0.01). Results from Knodell's scoring system were significantly correlated with computer morphometry, as follows: score 0, 2.7 ± 1.4; score 1, 5.7 ± 1.2; score 2, 7.7 ± 2.3; score 3, 10.7 ± 3.2; score 4, 21.8 ± 14.1. The trend was statistically significant by the Wilcoxon rank sum test. In conclusion, our computerized morphometry system is a reliable tool for the evaluation of the severity of liver fibrosis and can be used as a tool for the objective quantification of liver fibrosis.
Regulation of uridine diphosphate glucuronosyltransferase during the acute‐phase response
Authors: STRASSER SIMONE I , MASHFORD MAURICE L , DESMOND PAUL V
Published: March 2008

The acute‐phase response is associated with profound effects on oxidative drug metabolism. However, the effects on glucuronidation are poorly characterized. The aim of the present study was to determine the role of mediators of the acute‐phase response in the regulation of hepatic uridine diphosphate glucuronosyltransferase (UGT) expression. Family 1 and family 2 UGT isoforms were studied in turpentine‐injected rats and in primary hepatocyte cultures exposed to cytokines and/or dexamethasone. In the in vivo model, glucuronidation of p‐nitrophenol was unaffected, while testosterone glucuronidation was reduced to 65% of control (P < 0.01). In contrast, the mRNA level of UGT1*1 (which metabolizes bilirubin, not phenols) was depressed to 16% of control (P < 0.002), while the mRNA level of UGT2B3 (which metabolizes testosterone) was reduced to 53% (P < 0.05). In primary hepatocyte culture, dexamethasone treatment resulted in a 3.4‐fold induction of UGT1*1 mRNA levels (P < 0.001) but only a 1.5‐fold induction of UGT2B3 (P=0.1). Interleukin‐6 in the presence of dexamethasone resulted in a marked dose‐dependent suppression of both UGT1*1 and UGT2B3, although to different degrees. Interleukin‐1 had no effect on UGT mRNA levels. Thus, inflammatory mediators, such as cytokines and glucocorticoids, may be important determinants of both oxidative and conjugative drug metabolism by the liver.
An improved electrogastrographic system in measuring myoelectrical parameters
Authors: CHANG FULL‐YOUNG , LU CHING‐LIANG , LEE SHOU‐DONG , YU GEI‐LIAN
Published: March 2008

This study assessed the reliability of an improved electrogastrographic (EGG) system in recording stomach myoelectrical parameters and tried to establish the normal ranges of myoelectricity using this system. The analytical software of the current system mainly included an autoregressive modelling program to compute myoelectrical frequency and power. Forty healthy subjects were enrolled to receive myoelectrical measurement in two consecutively fasting and one postprandial 30 min sessions. The myoelectrical frequencies in both fasting and postprandial sessions were almost three cycles per min (c.p.m.) and showed little variation. The percentage of dominant frequencies (2.5–3.5 c.p.m.) in three sessions was approximately 80% while the computed myoelectrical powers in the first and second fasting sessions exhibited a significant correlation (r= 0.84, P < 0.001). Meal ingestion increased the myoelectrical powers by 6.8 dB compared with the second fasting recording (P < 0.001). The mean variation in myoelectrical amplitude for the ratio of second: first fasting session was 110.3 ± 88.8% (16–478%, median 88%). This new EGG system is, indeed, reliable for measuring myoelectrical frequency and power, whereas the interassay of recorded amplitudes appears markedly variable.
Usefulness of the [13C]‐urea breath test for detection of Helicobacter pylori infection in fasting patients
Authors: MIWA HIROTO , MURAI TOSHIO , OHKURA RYUICHI , NAGAHARA AKIHITO , WATANABE HARUO , TERAI TAKESHI , WATANABE SUMIO , SATO NOBUHIRO
Published: March 2008

Most of the reported [13C]‐urea breath test procedures use a test meal, which is believed to assist in the spread of the [13C]‐urea solution into the entire stomach, as results without a test meal may mainly reflect urease activity in the antrum. Yet, procedures for the [13C]‐urea breath test and interpretation of the obtained 13C excess value have not been well established. We carried out the present study to validate the usefulness of the [13C]‐urea breath test in fasting subjects and to establish cut‐off values. [13C]‐Urea breath tests were performed on 258 Helicobacter pylori‐positive and 151 ‐negative subjects (247 H. pylori positive and 26 negative prior to any H. pylori cure treatment and 125 H. pylori negative and 11 positive after undergoing H. pylori cure treatment). The breath test procedure was performed under the following conditions: an 8 h fast, mouth washing before and after dosing, administration of 100 mg [13C]‐urea, collection of breath sample in a plastic bag, a baseline and a 20 min sampling point and subject in a sitting position. Delta‐13C at the 20 min sampling point in H. pylori‐positive and ‐negative subjects was 31.0 ± 1.25 and 1.6 ± 0.11%o, respectively. Although the mean Δ13C value was greatest in duodenal ulcer or ulcer scar patients, there were no significant differences among mean Δ13C values in the various diseases. From Receiver Operator Characteristic curves and calculation of accuracy of the test, a cut‐off value of 5.0%o is considered to be appropriate for diagnosis of H. pylori infection, which provides 96.7% specificity and 96.5% sensitivity, suggesting that the [13C]‐urea breath test in the fasting state is as effective in detecting the presence of H. pylori as other reported methods.
Metronidazole‐ and clarithromycin‐resistant Helicobacter pylori in dyspeptic patients in western Sydney as determined by testing multiple isolates from different gastric sites
Authors: XIA HARRY HUA‐XIANG , KALANTAR JAMSHID , TALLEY NICHOLAS J
Published: March 2008

It is unknown whether antibiotic susceptibility testing of antral isolates alone is representative of Helicobacter pylori susceptibility. We aimed to determine: (i) the prevalence of metronidazole‐ and clarithromycin‐resistant strains in infected dyspeptic patients; and (ii) whether there is consistency in the susceptibility to metronidazole and clarithromycin among isolates cultured from different gastric sites. Antral, body and fundus biopsies were taken from 242 consecutive patients and cultured on blood agar under micro‐aerophilic conditions for 5–7 days. Isolates from 66 patients (13 had one, 15 had two and 38 had three isolates) were tested for susceptibility to metronidazole and clarithromycin using previously validated disc diffusion tests. Of the 66 patients, 42 (64%) had strains resistant to metronidazole while four (6.1%) had clarithromycin‐resistant strains. The prevalence of metronidazole resistance was not significantly different between men and women (65%vs 60%) or across different age groups. In five (9.4%) of the 53 patients with multiple isolates, discrepant results for metronidazole susceptibility were observed: susceptible antral and body isolates but resistant fundus isolates in two cases and susceptible antral isolates but resistant body and fundus isolates in the others. Clarithromycin susceptibilities were consistent among the isolates cultured from different gastric sites in all patients. It is concluded that metronidazole‐resistant strains of H. pylori are common while clarithromycin‐resistant strains are rare. Metronidazole susceptibility testing of antral isolates does not appear to be representative of isolates from the body and fundus in a subset of patients.
The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy
Authors: URATA JOJI , YAMASHITA YASUYUKI , TSUCHIGAME TADATOSHI , HATANAKA YOSHIMI , MATSUKAWA TETSUYA , SUMI SEIYA , MATSUNO YASUJI , TAKAHASHI MUTSUMASA
Published: March 2008

In addition to variceal bleeding, haematemesis may occur due to haemorrhagic gastritis in patients with portal hypertension. This has been known as portal hypertensive gastropathy (PHG). We have evaluated the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on portal venous pressure (PVP) and endoscopic gastric mucosal changes observed in patients with portal hypertension. We performed TIPS in 12 patients with complications due to portal hypertension as follows: variceal bleeding in nine patients (bleeding from oesophageal varices in seven and gastric varices in two), refractory ascites in three and haemorrhage from severe PHG in one. Endoscopic examinations were performed before and after TIPS for all patients. Changes of PVP and gastric mucosal findings on endoscopy were analysed. Before TIPS, PHG was seen in 10 patients. Portal venous pressure decreased from an average of 25.1 ± 8.8 to 17.1 ± 6.2 mmHg after TIPS (P < 0.005). On endoscopy, PHG improved in nine of 10 patients. Oesophagogastric varices improved in eight of 11 patients. In one patient with massive haematemesis, haemorrhage from severe PHG completely stopped after TIPS. Because TIPS effectively reduced PVP, this procedure appeared to be effective for the treatment of uncontrollable PHG.
Antibody dependent cell‐mediated cytotoxicity using hepatocellular carcinoma reactive monoclonal antibody
Authors: KUWATA TOMO , HARUTA IKUKO , HASEGAWA KIYOSHI , YAMAUCHI KATSUMI , HAYASHI NAOAKI
Published: March 2008

We have established monoclonal antibodies from mice immunized with the human hepatocellular carcinoma cell line, hu‐H2. One of the antibodies, designated 523(KY‐3), was reactive with this hepatocellular carcinoma cell line as well as with the human pancreatic cancer cell line, MIA. Another monoclonal antibody, 512(KY‐2), only reacted with the hepato‐cellular carcinoma cell lines. Neither antibody reacted with the colon cancer cell line CW3. Pretreatment of peripheral blood mononuclear cells with 523 resulted in enhancement of their natural cytotoxicity to hu‐H2 (9.0 vs 18.4% in subject 1, 3.5 vs 14.7% in subject 2, and 14.2 vs 31.0% in subject 3). In contrast, such antibody mediated enhanced natural cytotoxicity was not found by pretreatment of the same peripheral blood mononuclear cell with 512. With the similarity in reactivity of 523, this antibody dependent enhancement was found in natural cytotoxicity to hu‐H2 and MIA but not to CW3. Based on the facts that 523 did not have a direct cytopathic effect on these tumours and that this 523‐mediated enhanced natural cytotoxicity was inhibited by anti‐FcγRIII antibody, we concluded that the 523‐mediated enhanced cytotoxicity reflects its activity to induce antibody dependent cytotoxic cells. Thus, these results demonstrate that several distinct tumour‐specific antigens exist in hepatocellular carcinoma (HCC) and that one of them represents a potentially useful target for immunotherapy of human hepatocellular carcinoma.
Expression of insulin‐like growth factor II mRNA in hepatocellular carcinoma
Authors: NG IRENE OL , LEE JOYCE MF , SRIVASTAVA GOPESH , NG MATTHEW
Published: March 2008

Insulin‐like growth factor II (IGF‐II) is a mitogenic polypeptide closely related to insulin. Its gene has complex regulation of transcription, resulting in multiple mRNA initiated by different promoters. To study its role in hepatocarcinogenesis, we examined the expression of IGF‐II mRNA in hepatocellular carcinomas (HCC) and correlated it with the pathological features of the tumours. Using northern blot analysis, transcription of the normal adult promoter was repressed in all but two of the 30 HCC. Instead, there was re‐expression of two foetal transcripts (6 and 5 kb) in 12 tumours. In contrast, most (93.3%) of the non‐tumorous livers showed expression of adult transcript only, and there were three livers demonstrating expression of foetal transcripts in addition to the adult one. There was a significant association of IGF‐II expression with direct tumour invasion into the adjacent liver parenchyma but foetal expression did not influence other parameters directly related to tumour invasiveness, including venous permeation, formation of tumour microsatellites and positive resection margin. Besides, IGF‐II expression was significantly more frequently seen in tumours from older patients. To conclude, repression of normal adult promoter and re‐expression of foetal promoters of IGF‐II are common events in HCC. The observation that foetal IGF‐II expression was significantly more frequent in older patients suggests that spontaneous foetal expression of IGF‐II late in life may promote the growth of tumours which have already arisen through other mechanisms, but foetal reexpression itself is not enough to contribute to tumour progression.
Association between anomalous pancreaticobiliary ductal union and adenomyomatosis of the gall‐bladder
Authors: TANNO SATOSHI , OBARA TAKESHI , MAGUCHI HIROYUKI , FUJII TSUNESHI , MIZUKAMI YUSUKE , SHUDO RYUSHI , TAKAHASHI KUNIYUKI , NISHINO NORIYUKI , ARISATO SATOSHI , URA HITOSHI , KOHGO YUTAKA
Published: March 2008

A frequent association of biliary tract carcinoma and anomalous pancreaticobiliary ductal union (APBD) is well recognized, especially gall‐bladder carcinoma in undilated type APBD. However, little is known about the presence and incidence of adenomyomatosis (AMT) of the gall‐bladder, a presumed premalignant lesion, in patients with APBD. This retrospective study was conducted to elucidate the clinical features and incidence of AMT in APBD patients with relation to undilated type and dilated type APBD. We reviewed the clinicopathological records of 30 patients with APBD (28 women and two men) encountered during the past 10 years. Among them, 22 patients underwent cholecystectomy and the resected specimens were subjected to histopathological examinations. Eleven cases of APBD patients were undilated type and 11 cases were dilated type. Adenomyomatosis was found in six (55%) of 11 undilated type and one (9%) of 11 dilated type, and fundal type was predominantly observed in six (86%) of seven AMT. An overall incidence of AMT in APBD patients was 32%. An undilated type of APBD is frequently associated with AMT and we believe, therefore, that clinicians should be aware of a possible coexistence of APBD and AMT.
Colour Doppler‐guided spectral analysis of gall‐bladder wall flow
Authors: HAYAKAWA SHINYA , GOTO HIDEMI , HIROOKA YOSHIKI , ITOH AKIHIRO , TAKI TOMOYUKI , WATANABE YOSHIHIRO , HAYAKAWA TETSUO , NAITOH YASUO
Published: March 2008

For the purpose of the present study to diagnose gall‐bladder cancers, which cannot be detected or are only partly visible by conventional ultrasonography (US), we attempted differential diagnoses of 69 patients with gall‐bladder diseases (12 with gall‐bladder cancer, five with acute cholecystitis, 11 with chronic cholecystitis, 27 with cholesterol polyp and 14 with adenomyomatosis) using the evaluation of gall‐bladder wall blood flow (GWBF). GWBF was evaluated by colour Doppler‐guided spectral analysis (CDSA). Thirty‐three healthy volunteers were selected as controls at random. Two parameters of GWBF, namely flow velocity and resistive index (RI), were compared between patients with gall‐bladder diseases and healthy volunteers. GWBF could be ultrasonically evaluated in 92 (90%) of 102 subjects. All 12 patients with gall‐bladder cancer had a significantly rapid blood flow value compared with other patients and healthy volunteers. There was no significant difference in RI among patients and healthy volunteers. When cut‐off level of the flow velocity was set at 30 cm/s, gall‐bladder cancer could be diagnosed by flow velocity with 100% sensitivity (12/12) and 96% specificity (50/52). Using the same cut‐off level of the flow velocity, 17 patients were analysed prospectively. In four asymptomatic gall‐bladder cancers and two acute cholecystitis cases with some symptoms, the flow velocity was over 30 cm/s. In two of four patients with gall‐bladder cancer, only a part of the tumour was visualized on conventional abdominal US. In conclusion, CDSA was more useful for diagnosing gall‐bladder lesions than the conventional abdominal US due to estimation of arterial flow velocity in the gall‐bladder wall.
Expression of progastrin‐derived peptides and gastrin receptors in a panel of gastrointestinal carcinoma cell lines
Authors: KELLY APRIL , HOLLANDE FRÉDÉRIC , SHULKES ARTHUR , BALDWIN GRAHAM S
Published: March 2008

To assess the potential of gastrin receptor antagonists in the treatment of gastrointestinal cancer, the presence of an autocrine loop involving progastrin‐derived peptides has been investigated in two colorectal and one gastric carcinoma cell lines. Progastrin, glycine‐extended gastrin and amidated gastrin were detected in cell extracts or conditioned media by radio‐immunoassay. Low‐affinity binding sites for glycine‐extended gastrin and amidated gastrin were present, but high‐affinity binding sites were not detected with the appropriate iodinated ligands. In addition, neither glycine‐extended gastrin nor amidated gastrin in the concentration range 10 pmol/L‐10 nmol/L stimulated cell proliferation. We conclude that it is unlikely that the carcinoma cell lines LIM 1215, LIM 1839 and LIM 1899 use either amidated or glycine‐extended gastrins as extracellular autocrine growth factors.
CASE REPORT: Rupture of a gastric varix in liver cirrhosis associated with glycogen storage disease type III
Authors: HASHIMOTO MASAJI , WATANABE GORO , YOKOYAMA TSUYOSHI , TSUTSUMI KENJI , DOHI TAKEHIKO , MATSUDA MASAMICHI , OKUBO MINORU , NAKAMURA NORIMASA , TSURUMARU MASAHIKO
Published: March 2008

Glycogen storage disease type III, or Cori's disease, is caused by a deficiency of amylo‐1,6‐glucosidase (debranching enzyme), which leads to the storage of an abnormal glycogen in the liver and in skeletal and heart muscle. Glycogen storage disease type III is usually characterized by hepatic symptoms, growth failure and myopathy. Even though liver cirrhosis is reported, portal hypertension is a rare complication of this disease. We describe the case of a glycogen storage disease type III patient who was diagnosed at 3 years of age and developed complications (liver cirrhosis and rupture of a gastric varix) at 31 years of age. We discuss the histological progression to cirrhosis of the liver and describe the liver enzyme profile at 3 and 31 years of age.
Management guidelines for uninvestigated and functional dyspepsia in the Asia‐Pacific region: First Asian Pacific working party on functional dyspepsia
Authors: TALLEY NICHOLAS J , LAM SK , GOH KL , FOCK KM
Published: March 2008

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro‐oesophageal reflux, or gastric cancer but is most often due to functional (or non‐ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia‐Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new‐onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2–4 weeks with an empirical anti‐secretory or prokinetic agent, followed by investigation using non‐invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost‐effectiveness of the approaches recommended.