bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperglucagonaemia in cirrhotic patients and its relationship to the severity of cirrhosis and haemodynamic values
Authors: LIN HAN‐CHIEH , YANG MAY C‐M , HOU MING‐CHIH , LEE FA‐YAUH , HUANG YI‐TSAU , LIN LI‐FEN , LI SHU‐MIN , HWANG SHINN‐JANG , WANG SUN‐SANG , TSAI YANG‐TE , LEE SHOU‐DONG
Published: March 2008

Plasma glucagon concentrations were measured in 160 cirrhotic patients (Pugh's grade A in 52 patients, Pugh's grade B in 64 patients and Pugh's grade C in 44 patients). These values were compared with plasma glucagon concentrations in 57 age and sex‐matched healthy subjects. Systemic and portal haemodynamic measurements, effective renal plasma flow and creatinine clearance were recorded for each patient. Plasma glucagon levels were significantly increased in cirrhotic patients compared with healthy subjects. In addition, plasma glucagon levels were higher in cirrhotic patients with ascites than in those without ascites and were increased in relation to the severity of cirrhosis as assessed by Pugh's score. Multiple linear regression found that only Child‐Pugh's score was estimated to be an independent predictor of hyperglucagonaemia in cirrhotic patients. However, in patients with different degrees of oesophageal varices and in patients without oesophageal varices, plasma glucagon concentrations were no different among the different groups of patients, but were still higher than plasma glucagon concentrations in healthy subjects. In contrast, plasma glucagon levels were negatively correlated with mean arterial pressure and systemic vascular resistance. The results of the present study suggest that impairment of liver function plays, in part, a role in increased plasma glucagon levels observed in patients with cirrhosis. In addition, these data support the hypothesis that hyperglucagonaemia may contribute, at least in part, to the pathogenesis of peripheral arterial vasodilatation in cirrhosis with portal hypertension.
Case report: A patient with primary biliary cirrhosis and autoimmune haemolytic anaemia
Authors: YOSHIDA ERIC M , NANTEL STEPHEN H , OWEN DAVID A , GALBRAITH PAUL F , DALAL BAKUL I , BALLON HENRY S , KWAN SUSAN YL , WADE JOHN P , ERB SIEGFRIED R
Published: March 2008

Diseases of an autoimmune nature are well recognized in association with primary biliary cirrhosis. Although autoimmune thyroiditis and many rheumatological conditions are well described in primary biliary cirrhosis, autoimmune haematological diseases have been less well reported. We report on a 66 year old North American Indian man with coincident primary biliary cirrhosis and warm antibody haemolytic anaemia. This case report supports the suggestion of an association between autoimmune haemolytic anaemia and primary biliary cirrhosis.
Serum markers for fibrosis and plasma transforming growth factor‐β1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis
Authors: MURAWAKI YOSHIKAZU , IKUTA YUJIRO , NISHIMURA YUUKO , KODA MASAHIKO , KAWASAKI HIRONAKA
Published: March 2008

In order to elucidate collagen metabolism in hepatocellular carcinoma (HCC) tissue, we compared levels of different potential markers of collagen metabolism and plasma transforming growth factor‐β1 in patients with HCC and in patients with liver cirrhosis. Serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase‐1 in patients with HCC were significantly higher than those in patients with liver cirrhosis and increased with the size of the HCC tumour, whereas the serum levels of procollagen type III propeptide and type IV collagen 7S domain were similar in the two groups. In HCC, the increased plasma transforming growth factor‐β1 levels were closely correlated with serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase‐1. These findings suggest that, in HCC tissue, the intracellular biosynthesis of collagen is enhanced, whereas the secretion of procollagen is disturbed and the degradation of collagen is suppressed by the excess production of the tissue inhibitor of metalloproteinase‐1. The results also suggest that plasma transforming growth factor‐β1 plays an important role in the altered metabolism of collagen in HCC.
Differential effects between tauroursodeoxycholic and taurochenodeoxycholic acids in hepatic fibrosis: An assessment by primary cultured Ito and Kupffer cells from the rat liver*
Authors: SUGATA KOICHI , KAMIMURA SEIICHIRO , SHIJO HIROSHI
Published: March 2008

The pathogenesis of hepatic fibrosis in cholestasis is still unknown, except for endotoxaemia. There is a possibility that the elevation of serum bile acids in cholestasis may play an important role in hepatic fibrogenesis due to a reaction to perisinusoidal cells, such as Ito or Kupffer cells. To assess the effects of bile acids, we investigated the cell proliferation and collagen formation of primary cultured Ito cells that were incubated with a Kupffer cell conditioned medium (KCCM) treated with either taurochenodeoxycholic acid (TCDCA) or tauroursodeoxycholic acid (TUDCA) in short‐term (8 h) or long‐term (48 h) cultures. KCCM treated with TCDCA (100 μmol/L) but not with TUDCA increased cell proliferation of Ito cells in short‐term cultures and also partially elevated collagen formation by Ito cells in long‐term cultures. The release of tumour necrosis factor‐α (TNFα) from Kupffer cells was increased by TCDCA in short‐term cultures, but not in long‐term cultures. The release of transforming growth factor‐β1 (TGFβ1) from Kupffer cells was increased by TCDCA in long‐term cultures, but not in the short‐term cultures. TUDCA showed no significant effect on the release of TNFα and TGFβ1 from Kupffer cells. TUDCA or TCDCA itself showed no direct effect on the cell proliferation and collagen formation of Ito cells. In conclusion, these findings are thus considered to show the potentially important role of TCDCA on the development of hepatic fibrosis in the early phase of cholestasis without endotoxaemia.
Review: Regulation of liver regeneration by pro‐inflammatory cytokines
Authors: DIEHL ANNA MAE , RAI RUDRA
Published: March 2008

The liver has tremendous regenerative capacity. This distinguishes it from other vital organs (e.g. the brain, heart and lungs) that cannot replace functional tissue once it has been destroyed. Although hepatocytes rarely proliferate in the healthy adult liver, virtually all surviving hepatocytes replicate at least once after 70% partial hepatectomy. Therefore, partial liver resection has been used to characterize mechanisms that regulate liver regeneration. Residual hepatocytes up‐regulate both proliferative and liver‐specific gene expression in order to preserve tissue specific function. In addition, hepatocyte proliferation is tightly co‐ordinated to complement regenerative responses in hepatic nonparenchymal cells (e.g. endothelia, biliary epithelia, stellate and Kupffer cells), so that the entire organ can be reconstituted within days. Studies with neutralizing antibodies to tumour necrosis factor‐α (TNF) clearly demonstrate that, after partial hepatectomy, TNF promotes liver cell proliferation. The present review focuses on the regulation of the hepatocyte proliferative response by pro‐inflammatory cytokines.
Autoantibodies to M2 mitochondrial autoantigens in normal human sera by immunofluorescence and novel assays
Authors: OMAGARI KATSUHISA , ROWLEY MERRILL J , WHITTINGHAM SENGA , JOIS JENNIFER A , BYRON SARAH L , MACKAY IAN R
Published: March 2008

Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (anti‐M2), directed against the E2 subunits of the 2‐oxo‐acid dehydrogenase complexes (2‐OADC), chiefly pyruvate dehydrogenase complex (PDC‐E2). We present here a detailed study, based on a large panel of normal sera, of the specificity of tests for anti‐M2 by immunofluorescence and for anti‐PDC by other assays for the diagnosis of PBC. The assays for anti‐PDC included immunoblotting with bovine heart mitochondria, ELISA using recombinant PDC‐E2 and an enzyme inhibition assay using purified porcine PDC. The positivity rates for normal sera were 0 (0/170), 2 (4/201), 1.5 (3/198) and 0% (0/186) for immunofluorescence, immunoblotting, ELISA and the enzyme inhibition assay, respectively. The seven positive reactions detected either by immunoblotting (n= 4) or ELISA (n= 3) were negative by the other three assays and in no instance did biochemical indices give any indication of chronic liver disease. Thus, as judged by reactivity with normal sera, the specificity of a positive test for the antibody to the major M2 autoantigen (PDC‐E2) is 100% for immunofluorescence and the enzyme inhibition assay, 98% for immunoblotting and 98.5% for ELISA.
Review: Diagnosis of Helicobacter pylori infection
Authors: AZUMA T , KATO T , HIRAI M , ITO S , KOHLI Y
Published: March 2008

A number of diagnostic tests have been developed for the detection of H. pylori. Diagnostic techniques can be divided into invasive and noninvasive methods. The invasive methods require upper gastrointestinal endoscopy and involve culture of gastric biopsy specimens, examination of stained biopsies and detection of urease activity in the biopsies themselves. In addition, we have developed endoscopic diagnosis of H. pylori infection in gastric mucosa using phenol red dye‐spraying. The noninvasive methods include urea breath test and serological techniques. Although there has been considerable improvement in the techniques, a combination of at least two different techniques should be used in order to optimize the diagnostic yield. We recommend the use of one rapid test in the combination. The rapid urease test, cytology and the phenol red dye‐spraying endoscopy give results available before the patient leaves the endoscopy suite.
Long‐term follow‐up of gastric histology after Helicobacter pylori eradication
Authors: FORBES GEOFFREY M , WARREN J ROBIN , GLASER MARK E , CULLEN DIGBY JE , MARSHALL BARRY J , COLLINS BRENDAN J
Published: March 2008

Helicobacter pylori causes chronic active gastritis and is thought to be associated with the development of gastric atrophy, intestinal metaplasia and carcinoma. As the effect of H. pylori eradication on this process is poorly understood, we sought to determine the long‐term effects of H. pylori eradication on gastric histology. Fifty‐four patients with duodenal ulceration associated with H. pylori infection received H. pylori eradication therapy in 1985/86 and either remained infected (n= 22) or had the infection eradicated (n= 32); patients were followed up by endoscopy with gastric antral biopsy for 7.1 years (mean). Histopathological analysis of gastric antral mucosa from patients rendered H. pylori‐negative revealed a marked decrease in both inflammatory cells within the lamina propria and intraepithelial neutrophils and an increase in epithelial mucinogenesis. Gland atrophy remained unchanged in both H. pylori‐positive and ‐negative patients. When examined for the presence and severity of intestinal metaplasia, there was neither a difference between the two patient groups nor a change with time. These data demonstrate that significant long‐term improvements in gastric histology accompany H. pylori eradication when compared with histology in patients with persistent infection. Whether this confers a protective effect by reducing the risk of gastric carcinoma remains unknown.
Measurement of faecal α1‐antitrypsin: Methodologies and clinical application
Authors: CHOUDHARY SITARAM , GIBSON PETER R , DEACON MELISSA C , YOUNG GRAEME P
Published: March 2008

Presence of the serum protein, α1‐antitrypsin, in the faeces is a potentially useful marker for gastrointestinal disease and/or blood loss. In an effort to simplify faecal sampling procedures, we evaluated the performance of measuring α1‐antitrypsin in eluants of thin smears of faeces made on filter paper, relative to conventional measurement in aqueous extracts of stool. Faecal specimens and smears were collected from healthy subjects (n= 22) and from patients with gastrointestinal bleeding (n= 12) or inflammation (n= 22), colorectal neoplasia (n= 15), or miscellaneous diseases with a low risk of excessive faecal protein loss (n= 30). α1‐Antitrypsin was measured by ELISA and haem porphyrins (as a measure of blood loss) by HemoQuanttm. Results from smears were highly correlated (r = 0.81; P < 0.001) with faecal α1‐antitrypsin. The smear method detected an elevated faecal α1‐antitrypsin with 93% specificity and 75% sensitivity. Sensitivity was high (> 88%) where levels were markedly elevated in inflammatory and bleeding groups and low (< 62%) where abnormal levels were mildly elevated (neoplasia and miscellaneous groups). Elevated α1‐antitrypsin detection by either method positively predicted > 90% of patients with gastrointestinal inflammatory disease when levels were elevated 6‐fold and 1.5‐fold or more, respectively. In 15 patients with colorectal neoplasia, faecal α1‐antitrypsin was elevated in 10 patients, haem porphyrins in nine patients and either in 12; however, smear eluant levels were elevated in only six patients. Blood loss was probably a major contributor to elevated faecal α1‐antitrypsin in some patients but not in the inflammatory group as a whole. The sampling and aesthetic advantages of the smear eluant method are offset by reduced sensitivity, precluding its use as a screening test for colorectal neoplasia. However, its performance in predicting inflammatory disease is equivalent to that of conventional measurement and warrants a prospective evaluation as an early investigative test. Concurrent evaluation of blood loss may improve its interpretation.
Current concepts of hepatic uptake, intracellular transport and biliary secretion of bile acids: Physiological basis and pathophysiological changes in cholestatic liver dysfunction*
Authors: AZER SAMY A , STACEY NEILL H
Published: March 2008

Hepatic sinusoidal uptake of bile acids is mediated by defined carrier proteins against unfavourable concentration and electrical gradients. Putative carrier proteins have been identified using bile acid photoaffinity labels and more recently using immunological probes, such as monoclonal antibodies. At the sinusoidal domain, proteins with molecular weights of 49 and 54 kDa have been shown to be carriers for bile acid transport. The 49 kDa protein has been associated with the Na+‐dependent uptake of conjugated bile acids, while the 54 kDa carrier has been involved in the Na+‐independent bile acid uptake process. Within the hepatocyte, cytosolic proteins, such as the glutathione S‐transferase (also designated the Y protein), the Y’ binders and the fatty acid binding proteins, are able to bind bile acids and possibly facilitate their movement to the canalicular domain. At the canalicular domain a 100 kDa carrier protein has been isolated and it has been shown by several laboratories that this particular protein is concerned with canalicular bile acid transport. The system is ATP‐dependent and follows Michaelis‐Menten kinetics. Interference with bile acid transport has been demonstrated by several chemicals. The mechanisms by which these chemicals inhibit bile acid transport may explain the apparent cholestatic properties observed in patients and experimental animals treated with these agents. Several studies have shown that Na+/K+‐ATPase activity is markedly decreased in cholestasis induced by ethinyloestradiol, taurolithocholate and chlorpromazine. However, other types of interference have been described and the cholestatic effects may be the result of several mechanisms. Cholestasis is associated with several adaptive changes that may be responsible for the accumulation of bile acids and other cholephilic compounds in the blood of these patients. It may be speculated that the nature of these changes is to protect liver parenchymal cells from an accumulation of bile acids to toxic levels. However, more detailed quantitative experiments are necessary to answer questions with regard to the significance of these changes and the effect of various hepatobiliary disorders in modifying these mechanisms. It is expected that the mechanisms by which bile acid transport is regulated and efforts to understand the molecular basis for these processes will be among the areas of future research.
Interferon‐α therapy for individuals with normal serum alanine aminotransferase levels before treatment
Authors: ORITO ETSURO , MIZOKAMI MASASHI , SUZUKI KAORU , OHBA KEN‐ICHI , OHNO TOMOYOSHI , MIZUNO MAKOTO , IIJIMA YOSHIHIKO , SAITOH HIROSHI , NEMOTO AKIRA , NUKUTA NOBUO
Published: March 2008

While interferon (IFN) therapy is approved for patients with chronic hepatitis C infection, the effectiveness of IFN therapy for anti‐hepatitis C virus (HCV)‐positive individuals with normal ALT levels remains poorly understood. Twenty‐five individuals (M:F = 9:16; age = 51.8±15.1 years) who showed a normal alanine aminotransferase (ALT) level (< 30 IU/L) at least 6 months before treatment and were positive for both anti‐HCV and serum HCV‐RNA by reverse transcription polymerase chain reaction (RT‐PCR) were studied. Of these, 16 received IFN therapy for 24 weeks (780 million units total IFN‐α2b) and nine were followed for 12 months as controls. The serum HCV‐RNA level was determined by bDNA assay and HCV genotype was detected by enzyme immunoassay. All were shown to have chronic hepatitis by liver biopsy. Six (37.5%) of 16 individuals lost serum HCV‐RNA by RT‐PCR 6 months after cessation of therapy (complete response; CR), while the remaining individuals were defined as non‐responders (NR). Of the six individuals in the CR group, five had HCV type 2 infection, compared with none of 10 individuals in the NR group (P < 0.01). There was a trend towards a lower pretreatment viraemia level in the CR group than in the NR group. These data suggest that IFN therapy for individuals with HCV type 2 infection and normal ALT levels was effective
Natural anticoagulants and the liver
Authors: CASTELINO DANIEL J , SALEM HATEM H
Published: March 2008

The regulation of blood coagulation is dependent on a complex interplay between procoagulant, anticoagulant and fibrinolytic proteins. Most of these proteins are synthesised in the liver and their levels are altered in patients with liver disease. The liver also plays an important role in the regulation of haemostasis throughout the clearance of activated clotting factors. It is therefore not surprising that the critically balanced coagulation system is dysregulated in patients with liver disease. In moderate liver failure bleeding disorders predominate, whereas in more advanced liver disease intravascular coagulation is commonly observed and contributes to the overall dysregulation of blood coagulation. In some patients, liver disease can be primarily caused by an abnormality of the coagulation system. These patients usually have a hypercoagulable state caused by a deficiency of a component of the natural anticoagulant system. These include protein C, protein S and antithrombin III. More recently, activated protein C resistance caused by a point mutation in the Factor V gene has been identified as an important risk factor for thrombosis. In these patients the abnormal Factor V is resistant to cleavage by activated protein C resulting in ongoing uncontrolled procoagulant drive. Both hepatic and portal vein thrombosis have been reported in these patients. Appropriate management of these patients should include a thorough assessment of their natural anticoagulant proteins and exclusion of activated protein C resistance as the cause of their thrombotic disorder.
Effect of tauro‐α‐muricholate and tauro‐β‐muricholate on oestradiol‐17β‐glucuronide‐induced cholestasis in rats
Authors: TAKIKAWA HAJIME , SANO NAOYO , AISO MITSUHIKO , TAKAMORI YORIYUKI , YAMANAKA MASAMI
Published: March 2008

The effect of tauro‐β‐muricholate (βMC‐tau) and tauro‐α‐muricholate (αMC‐tau) on oestradiol‐17β‐glucuronide (E217G)‐induced cholestasis was compared with that of taurourso‐deoxycholate (UDC‐tau) in rats. Like UDC‐tau, αMC‐tau and βMC‐tau infused at the rate of 0.2 μmol/min per 100 g bodyweight (BW) completely inhibited the cholestasis induced by E217G infused at the rate of 0.06 μmol/min per 100 g BW for 20 min. These findings indicate that βMC‐tau and αMC‐tau are useful in protecting against various types of experimental cholestasis, as well as against bile acid‐induced cholestasis.
A prospective clinical study of isoniazid‐rifampicin‐pyrazinamide‐induced liver injury in an area endemic for hepatitis B
Authors: HWANG SHINN‐JANG , WU JAW‐CHING , LEE CHUN‐NIN , YEN FU‐SHUN , LU CHING‐LIANG , LIN TAO‐PING , LEE SHOU‐DONG
Published: March 2008

In order to evaluate the incidence, predisposing factors and clinical course of antituberculous drug‐induced liver injury in hepatitis B surface antigen (HBsAg)‐positive carriers and non‐carriers, in an area endemic for hepatitis B, we prospectively followed 240 patients (154 male, 86 female; mean age 40 years) who had received daily isoniazid, rifampicin, ethambutol and pyrazinamide for the treatment of pulmonary tuberculosis. Patients with heavy alcohol consumption, with pretreatment serum alanine aminotransferase (ALT) elevation and who had less than 3 months post‐treatment follow‐up were excluded from the study. Thirty‐one (13%) patients were positive for serum HBsAg before treatment. Sixty‐three (26%; 95% CI: 21–32%) patients developed antituberculous drug‐induced liver injury. The incidence of drug‐induced liver injury was significantly more frequent in patients > 35 years of age than in patients > 35 years of age (33 vs 17%; P < 0.05), but was not different between HBsAg carriers and non‐carriers (29 vs 26%; P > 0.05). Using step‐wise logistic regression analysis, patient age > 35 years was the only independent variable for predicting antituberculous drug‐induced liver injury, while sex, acetylator phenotype, HBsAg carrier status and severity of tuberculosis were not. The peak serum ALT levels in antituberculous drug‐induced liver injury were not significantly different between HBsAg carriers and non‐carriers. Only one 61‐year‐old HBsAg carrier developed severe jaundice after 6 months antituberculous therapy; he subsequently died of hepatic failure. In conclusion, the incidence of antitubercuious drug‐induced liver injury was significantly higher in patients > 35 years of age than in patients > 35 years of age, but was not different between HBsAg carriers and non‐carriers. Mortality occurred in an aged HBsAg carrier superimposed with antituberculous drug‐induced liver injury.
Hepatitis C virus (HCV) genotypes and chronic liver disease in Pakistan
Authors: SHAH HASNAIN A , JAFRI WASIM , MALIK IMTIAZ , PRESCOTT LINDA , SIMMONDS PETER
Published: March 2008

Hepatitis C virus (HCV) is classified into different types depending on nucleotide sequence variability. Detailed information on the distribution of various HCV genotypes in some geographical areas is available but little is known about Pakistan. In this study, a 5’ non‐coding region (NCR)‐based restriction fragment length polymorphism (RFLP) genotyping assay was used to investigate the genotype distribution in a large series of HCV‐infected patients in Karachi, Pakistan. Serum samples from 74 hepatitis B surface antigen (HBsAg)‐negative patients with a clinical diagnosis of chronic liver disease (60 patients) and hepatocellular carcinoma (HCC) (14 patients) were assayed for anti‐HCV antibody by second generation enzyme immunoassay and 48 were confirmed anti‐HCV‐positive (33 males, 15 females). Other causes of chronic liver disease (e.g. haemochromatosis, Wilson's disease and immunemediated injury) were ruled out. Liver biopsy was done in 27/48 anti‐HCV‐positive patients and in all HCC patients. Genotypes were determined for 45/48 anti‐HCV‐positive study patients; 39/45 (87%) were type 3; four (9%) were type 1; one was type 2; and one was type 5. Past blood transfusion was the main identifiable risk factor found in 10 patients, all type 3. Seven of the 14 HCC patients were anti‐HCV positive, (six were type 3). Most patients with hepatitis C presented with established cirrhosis and complications of portal hypertension and liver failure. In conclusion: (i) genotype 3 is the most common isolate in HCV‐associated chronic liver disease in Pakistan; (ii) a significant proportion of HBsAg‐negative cirrhotics are non‐B, non‐C in aetiology; and (iii) half of the patients with HCC have serological evidence of HCV infection.
Diagnosis and treatment of superficial oesophageal carcinoma
Authors: CHEN YI‐JEN , LEE MENG‐DAR , CHEN PAO‐HUEI
Published: March 2008

Oesophageal carcinoma is a major cause of cancer death in certain parts of the world. Early detection provides the only chance of cure. In this study, one female and nine male patients with superficial oesophageal carcinoma were investigated to determine the pertinent clinical and pathological features. All male patients were smokers and six patients drank various amounts of alcohol on a daily basis. Histologically, five cases were confined within the mucosal layer and five within the submucosal layer. All five mucosal cancer cases and two of the live submucosal cancer cases were asymptomatic. Endoscopically, all five mucosal cancer patients had flat lesions, whereas the five submucosal cancer tumours appeared either protruding or depressed. Barium oesophagography failed to demonstrate the lesions in four of five mucosal cancer and one of five submucosal cancer cases. Endoscopic ultrasonography correctly detected the depth of cancer invasion in six out of eight superficial oesophageal carcinoma cases. All patients received a one‐stage operation that included oesophagectomy and lymph node dissection. All five mucosal cancer patients had no lymph node involvement and have experienced no tumour recurrence. Among them, one who had concomitant hepatocellular carcinoma died early. Of the five submucosal cancer cases, four died 1–5 years after the operation. It is concluded that oesophageal carcinoma is curable in its early stage. Physicians should be alert while performing endoscopic examination. We believe that the dyeing technique is a useful adjunct to endoscopic examination.
Gastro‐oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop
Authors: SCHWAB GP , BLUM AL , BODNER E , DALLEMAGNE B , GLASER K , KOOP H , PACE F , RÖSCH W , SIEWERT JR , WETSCHER G
Published: March 2008

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.
Absorption of unconjugated bile acids and tauroursodeoxycholate in the rat intestine
Authors: TAKIKAWA HAJIME , YOKOTE MICHIKO , SANO NAOYO , KUYAMA YASUSHI , YAMANAKA MASAMI
Published: March 2008

The absorption of ursodeoxycholate and its tauro‐conjugate by the jejunum and the terminal ileum of rat intestine was compared with that of other unconjugated bile acids and taurocholate. In the ligated jejunum, the efficacy of absorption of unconjugated bile acids was in the following order: ursodeoxycholate = deoxycholate > chenodeoxycholate = cholate > lithocholate. This order cannot be explained by the theory that the passive diffusion of bile acids is faster the less hydroxyl bonds in the molecule. These findings on the unconjugated bile acids in the ligated jejunum were further confirmed by perfusion experiments. In the ligated terminal ileum, ursodeoxycholate, cholate and deoxycholate were absorbed as fast as taurocholate or tauroursodeoxycholate, whereas absorption of chenodeoxycholate was significantly slower. The Na+‐dependency of the absorption of ursodeoxycholate and cholate in the terminal ileum was confirmed by perfusion studies. In conclusion, intestinal absorption of ursodeoxycholate was efficient in both the jejunum and ileum and these results may contribute to the high availability of ursodeoxycholate in various hepatobiliary diseases.
Dose‐related effects of dietary iron supplementation in producing hepatic iron overload in rats
Authors: PLUMMER JOHN L , MACKINNON MALCOLM , CMIELEWSKI PATRICIA L , WILLIAMS PHIL , AHERN MICHAEL J , ILSLEY ANTHONY H , HALL PAULINE DE LA M
Published: March 2008

The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose‐related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8–16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8‐fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade III‐IV) hepatic iron loading can be achieved with minimal adverse effects on the animals’ overall health.
HCV and HBV coexist in HBsAg‐negative patients with HCV viraemia: Possibility of coinfection in these patients must be considered in HBV‐high endemic area
Authors: LEE DONG‐SOON , HUH KWANG , LEE ENU‐HEE , LEE DONG‐HO , HONG KI‐SOOK , SUNG YOUNG‐CHUL
Published: March 2008

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with hepatitis B virus (HBV) infection in Korea. The role of HBV and hepatitis C virus (HCV) in HCC patients who are negative for hepatitis B surface antigens (HBsAg) remains poorly defined. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. Therefore, routine enzyme immunoassay may not detect HBV, in spite of the presence of HBV viraemia in low titres. The aim of this study was to confirm the coexistence of HBV viraemia in hepatitis C‐infected patients with HCC who have apparent HBsAg seronegativity and to establish the need for clinical reinterpretation of enzyme immunoassay (EIA) serological tests of HBsAg in patients with HCV viraemia and HCC. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and the coinfection rate of HCV and HBV investigated. Sera were obtained from 16 patients who were both anti‐HCV and HCV‐RNA positive but HBsAg negative, and tested for HBV by polymerase chain reaction (PCR). Eleven non‐A and non‐B chronic hepatitis patients without HCC who had the same profiles of anti‐HCV, HCV‐RNA, and HBsAg were tested for HBV by PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non‐A and non‐B chronic hepatitis patients without HCC; both were anti‐HCV, HCV‐RNA, and HBsAg negative and tested for HBV PCR. Of the 616 patients with HCC, 450 (73.1%) had current HBV infection, 48 (7.8%) had anti‐HCV antibodies, and nine (1.5%) had viral markers of both HCV and HBV by serological profiles. Of the 27 patients with HCV viraemia and HBsAg seronegativity (16 with HCC; 11 with non‐A non‐B chronic hepatitis), 14 (51.9%) showed HBV viraemia by PCR. In contrast, of the 75 patients in the control group (45 with HCC; 30 with non‐A and non‐B chronic hepatitis) who were both HCV PCR negative and HBsAg negative, five (11.1%) showed HBV viraemia by PCR. The PCR for HBV revealed coexistent HBV viraemia in HCV viraemia patients, despite HBsAg negativity by EIA. In HBV‐endemic areas, the possibility of coinfection of HBV in HBsAg‐negative patients with HCV viraemia should be considered and molecular analysis for HBV‐DNA performed.
Relationship between interleukin‐8 levels and myeloperoxidase activity in human gastric mucosa
Authors: SASAYAMA YOSHIAKI , KAWANO SUNAO , TSUJI SHINGO , FUSAMOTO HIDEYUKI , KAMADA TAKENOBU , FUKUI HIROYUKI , YONEDA SHOTARO , OKISHIO TATSUO
Published: March 2008

Although interleukin (IL)‐8 is well known as a chemotactic agent for neutrophil migration in vitro, the relationship between IL‐8 activity and the degree of neutrophil infiltration in gastric mucosa is still unclear. In the present study, we investigated IL‐8 and myeloperoxidase activity, a marker of neutrophil infiltration, in gastric antral mucosa using biopsy samples in 23 patients with no gastric lesions. The results indicate that there is a good correlation between IL‐8 and myeloperoxidase activity (y = 0.173x + 13.9; r = 0.49, P<0.01). Furthermore, IL‐8 and myeloperoxidase activity are significantly higher in Helicobacter pylori‐positive patients than in H. pylori‐negative patients. In conclusion, an increase of IL‐8 activity in the gastric mucosa causes increased neutrophil infiltration in human gastric mucosa and H. pylori infection acclerates these reactions in the mucosa.
Multiple hilar cysts of the liver in patients with alcoholic cirrhosis: Report of three cases
Authors: FUJIOKA YASUNORI , KAWAMURA NAOYUKI , TANAKA SHINYA , FUJITA MIRI , SUZUKI HIROAKI , NAGASHIMA KAZUO
Published: March 2008

The present report concerns the clinicopathological study of three patients with alcoholic cirrhosis (a 40‐year‐old man, a 52‐year‐old woman and a 48‐year‐old man) who had multiple cysts along their intrahepatic bile ducts. The cysts were visible on gross examination of the liver and, in two cases, an enlargement of the cysts had been detected in abdominal computed tomography scans performed 1 year apart. Histologically, the cysts consisted of proliferating and dilated peribiliary glands. The cysts occasionally compressed the original bile ducts. The latter showed mucosal hyperplasia with antral‐type gland metaplasia. Neoplastic changes and necroinflammation were not seen. Immuno‐histochemical assays revealed that the peribiliary glands and antral‐type glands expressed not only cytokeratin and carbohydrate antigen 19‐9, but also c‐MET protein, the hepatocyte growth factor receptor which may be related, at least in part, to the cystic dilatation of the peribiliary glands.
Evaluation of the timing of the booster injection after a primary vaccination against hepatitis A
Authors: FUJIYAMA SHIGETOSHI , ODOH KOICHI , TANAKA MOTOHIKO , KURAMOTO IZUMI , TOMITA KIMIO
Published: March 2008

To evaluate the long‐term efficacy and the timing of booster injection of a lyophilized, inactivated hepatitis A vaccine (HAV), we studied the acquired anti‐hepatitis A virus titres in 45 subjects who received either two or three doses of the vaccine. With three doses ≥ 0.5 μg administered at 0, 1 and 6 months, antibody titres increased to approximately half those seen in people with a history of natural hepatitis A infection. Although the titres decreased gradually, all subjects remained anti‐HAV positive at least 5 years after the third injection. The geometric mean titre exceeded 100 mlU/mL, which approximated the highest titre obtainable by the inoculation of immune serum globulin. A prompt antibody reaction was seen with two doses administered 2 weeks apart, with the titres achieved being 5.6‐fold the peak titres obtained by the inoculation of immune serum globulin. All 33 subjects were antibody positive 18 months after the first injection, but some became seronegative by 30 months, suggesting that a third booster dose would be desirable at 18 months.
Hepatitis C virus genotypes in a cohort of Australian blood donors and haemophiliac and liver transplant patients
Authors: CHEN JJ , McGUINNESS PH , KOOREY DJ , RICKARD K , WYLIE B , McCAUGHAN GW
Published: March 2008

The aim of the present study was to characterize hepatitis C virus (HCV) genotypes using the INNO‐LiPA HCV line probe assay and direct sequencing from three different HCV‐RNA‐positive (serum) groups: (i) blood donors (n= 59); (ii) haemophiliacs (n= 43); and (iii) patients undergoing liver transplantation (n= 26). Of 128 HCV‐RNA‐positive samples, 74 (58%) were genotype 1. Of these, 41 were genotype 1a, 32 were genotype 1b and one was genotype 1 indeterminate. Of the remaining 54 samples, seven (5%) were genotype 2a, two (2%) were genotype 2b, 26 (20%) were genotype 3a, three (2%) were genotype 4a, while 16 (12.5%) were of a mixed genotype. There was no significant difference between the three groups with regard to the prevalence of any specific genotype. However, in blood donors and haemophiliac patients there was a statistically significant difference in the occurrence of genotype 3a in patients with elevated alanine aminotransferase (ALT) levels (30.3%) compared with those patients with persistently normal ALT levels (5.6%; P= 0.004; x2) Genotype 3a was also uncommon in liver transplant patients (one of 14) with ‘sporadic’ HCV infection. Genotype 4a was detected only in liver transplant patients. These patients had originated from Egypt (n= 1), Italy (n= 1) and Romania (n= 1).
CLINICAL UPDATE: Management of acute pancreatitis
Authors: HABER PAUL S , PIROLA ROMANO C , WILSON JEREMY S
Published: March 2008

The management of acute pancreatitis commences with confirming the diagnosis and establishing the aetiology. Improved methods of assessing the biliary tree may reduce the number of patients regarded as having idiopathic pancreatitis. Detailed clinical and laboratory protocols, designed to assess severity, have no major advantage over clinical assessment. The contrast‐enhanced computed tomography scan is important to assess the degree of pancreatic necrosis and to detect local complications. The treatment of pancreatitis continues to be largely supportive. However, controlled studies support the use of antibiotics in severe acute pancreatitis and indicate a possible role for the use of octreotide and antioxidants. The place of endoscopic and surgical intervention is becoming better defined. Once an attack has passed, further investigation is often required in a bid to prevent further episodes of inflammation.
>CASE REPORT: Eosinophilic colitis with high antibody titre against Ascaris suum
Authors: TAKEYAMA YASUAKI , KAMIMURA SEIICHIRO , SUZUMIYA JUNJI , OH KOHJI , OKUMURA MAKOTO , AKAHANE HIROSHIGE , MARUYAMA HARUHIKO , NAWA YUKIFUMI , OHKAWARA TSUNENOBU , KIKUCHI MASAHIRO
Published: March 2008

Eosinophilic gastroenteritis (EGE) is an inflammatory disease characterized by eosinophilic infiltration of the gastrointestinal tract accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. Although the precise aetiology of EGE remains to be determined, contribution of allergic process to certain allergens, such as foods, drugs and parasites, has been repeatedly proposed as the pathogenesis of the disease. Here we report on a rare case of a woman who had extensive eosinophilic infiltration in the descending and rectal colon with a high titre of IgG antibody against Ascaris suum. The patient was successfully treated with prednisolone.
CASE REPORT: Primary cystic keratinizing squamous cell carcinoma of the liver in a patient with treated nasopharyngeal carcinoma
Authors: CHOU YUH‐YU , LEE WEI‐JEI , SU CHENG‐TAU , HSU HEY‐CHI
Published: March 2008

Primary squamous cell carcinoma of the liver is very rare; only 18 cases have been recorded. In the present report we document an additional case who had a unique history of stage III non‐keratinizing nasopharyngeal carcinoma treated with a full course of radiotherapy in July 1993. Two small hypoechoic cyst‐like lesions in the left hepatic lobe were identified at the same time. In July 1995 the 50‐year‐old patient reported to be suffering from abdominal fullness and tenderness. A large hypodense tumour was demonstrated in the left hepatic lobe by abdominal echography. The patient was diagnosed as having metastatic carcinoma and received two courses of pre‐operative chemotherapy followed by left lobectomy of the liver and resection of adherent tissues on 9 August 1995. Pathological study demonstrated a large hepatic cystic keratinizing squamous cell carcinoma, which most likely arose from a solitary hepatic cyst. Tumour seedings, probably secondary to tumour rupture, were also revealed on the omentum, peritoneum and diaphragm. However, regional lymph nodes were free of tumour. Systemic work‐up failed to demonstrate evidence of local recurrence of nasopharyngeal carcinoma, metastatic lesion or any second primary tumour site.
Plasma concentrations of cyclic 3′,5′‐guanosine monophosphate in patients with cirrhosis: Relationship with atrial natriuretic peptide and haemodynamics
Authors: KIRSTETTER PHILIPPE , MOREAU RICHARD , VACHIERY FLORENCE , GADANO ADRIAN , SOUPISON THIERRY , PILETTE CHRISTOPHE , PUSSARD ERIC , CAILMAIL STEPHANE , TAKAHASHI HAKUO , LEBREC DIDIER
Published: March 2008

Little is known about the plasma concentrations of cyclic 3′,5′‐guanosine monophosphate (cGMP) in patients with cirrhosis. However, plasma cGMP concentrations provide information on cellular cGMP production by particulate guanylyl cyclases (which are stimulated by natriuretic peptides, such as atrial natriuretic peptide; ANP). In contrast, because intracellular cGMP elicits vasorelaxant mechanisms, plasma cGMP concentrations may be related to haemodynamic alterations in patients with cirrhosis. The aim of the present study was to measure plasma cGMP concentrations in patients with cirrhosis and controls and to examine the relationship between cGMP levels and plasma ANP concentrations and haemodynamic values. Plasma concentrations of cGMP and ANP and splanchnic and systemic haemodynamics were measured in 23 subjects; 13 subjects had cirrhosis and 10 were controls. All subjects had normal glomerular filtration. Plasma cGMP concentrations were significantly higher in patients (6.5±0.8 pmol/mL) than in controls (2.7±0.4 pmol/mL), while plasma ANP concentrations did not significantly differ between the two groups (127±22 and 123±27 pg/mL, respectively). In patients with cirrhosis, no significant correlation was found between plasma cGMP concentrations and plasma ANP concentrations, hepatic venous pressure gradient, cardiac output or systemic vascular resistance. In conclusion, in patients with cirrhosis, increased plasma cGMP concentrations may be due to an activation of particulate guanylyl cyclases by natriuretic peptides other than ANP. The present study suggests that plasma cGMP concentrations are not related to cirrhosis‐induced haemodynamic alterations.
Effects of glycyrrhizin on immune‐mediated cytotoxicity
Authors: YOSHIKAWA MASAHIDE , MATSUI YUJI , KAWAMOTO HIROSHI , UMEMOTO NORIE , OKU KAZUMI , KOIZUMI MASAKI , YAMAO JUNICHI , KURIYAMA SHIGEKI , NAKANO HIROSHI , HOZUMI NOBUMICHI , ISHIZAKA SHIGEAKI , FUKUI HIROSHI
Published: March 2008

Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune‐mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)‐α is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase‐lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune‐mediated cytotoxicity using an antigen‐specific murine CD4+ T hybridoma line, which exhibits cytotoxicity against antigen‐presenting cells after stimulation with specific antigen, and a murine TNF‐α‐sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen‐presenting cells and also suppressed TNF‐α‐induced cytotoxicity in the TNF‐α‐sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune‐mediated cytotoxicity against hepatocytes.
Relationship between cellular ATP content and cellular functions of primary cultured rat hepatocytes in hypoxia
Authors: HAYASHI KATSUHIRO , OCHIAI TOSHIMASA , ISHINODA YOSHIHIRO , OKAMOTO TAKESHI , MARUYAMA TOSHIHIRO , TSUDA KAZUNORI , TSUBOUCHI HIROHITO
Published: March 2008

The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo, perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long‐term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 × 104 and 5 × 104 cells/0.18 mL per cm2 for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long‐term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis.
Endothelin‐induced vasoconstriction in isolated perfused liver preparations from normal and cirrhotic rats
Authors: ELLIOT ALAN J , VO LIEM T , GROSSMAN VIRGINIA L , BHATHAL PRITHI S , GROSSMAN HOWARD J
Published: March 2008

Isolated, perfused rat liver preparations (IPRL), obtained from rats with carbon tetrachlorideinduced cirrhosis and normal controls, were used to investigate responses to the vasoactive peptide endothelin‐1 (ET‐1). The mean perfusion resistance (R) of cirrhotic IPRL was significantly greater than that of controls (2.63 ± 0.24 vs 1.54 ± 0.14 mmHg/mL per min per g; P < 0.01). Both control and cirrhotic IPRL demonstrated a concentration‐related increase in resistance (ΔR) in response to ET‐1, with a minimum effective concentration of approximately 3 × 10−11 mol/L. The EC50 (‐log of the 50% effective concentration) was not significantly different between cirrhotic and control IPRL (8.48 ± 0.19 and 8.79 ± 0.11, respectively); however, the maximum response to ET‐1 was significantly greater in cirrhotic preparations (R: 10.4 ± 2.2 vs 4.4 ± 0.5 mmHg/mL per min per g, P < 0.01; DR, 7.8 ± 2.1 vs 2.8 ± 0.4 mmHg/mL per min per g, P < 0.01). Following maximal stimulation by ET‐1, the mean portal‐hepatic venous pressure gradient at a physiological flow rate of 1 mL/min per g was approximately 90% greater across cirrhotic IPRL than that across normal IPRL (11.2 ± 2.0 vs 5.9 ± 0.9 mmHg, respectively; P < 0.05). These results support the hypothesis that endogenously released ET‐1 has a significant influence on the portal vascular resistance of cirrhotic liver in vivo and has an important role in the pathogenesis of portal hypertension.