bluuebunny/crossref_metadata_2025 huggingface dataset:
BRIEF COMMUNICATION: Smoking and duodenal blood flow
Authors: GUSLANDI M , SORGHI M , FOPPA L , TITTOBELLO A
Published: March 2008

Smoking promotes an increase in both the incidence and the recurrence of duodenal ulcers, but the mechanisms responsible for its adverse effects on the duodenal mucosa are still poorly understood. The aim of the present study was to investigate the effect of chronic cigarette smoking on duodenal blood flow. In 20 dyspeptic patients (10 non‐smokers and 10 smokers) with endoscopically normal duodenum, mucosal blood flow was measured in the duodenal bulb by laser Doppler flowmetry during endoscopy. Basal bulbar perfusion was found to be significantly lower (P < 0.05) in smokers. Our results suggest that duodenal blood flow is reduced in heavy smokers. This may promote duodenal damage because of both local ischaemia and the reduced secretion of protective bicarbonate.
Development of gastroenterology in Bangladesh
Authors: HASAN M , KHAN AK AZAD
Published: March 2008

Diseases of the gastrointestinal tract and liver are very common in Bangladesh. Gastroenterology as a dedicated specialty was initiated in 1977 at the Institute of Postgraduate Medicine and Research in Dhaka. One more centre was set up later and these centres are providing specialized diagnostic and therapeutic services. These centres are also imparting training in endoscopy and 49 endoscopists trained so far are providing services in 22 centres around the country. Clinical gastroenterologists are also being trained in a 3 year Master's degree course and three specialists have already completed this. A Gastroenterology Society was formed in 1988 and has held three national scientific conferences and 20 regional meetings. Research in special problems of the country has also been initiated and work on aspects of peptic ulcer disease, chronic calcific pancreatitis and chronic viral hepatitis has been conducted. The demand for gastrointestinal services is high and the specialty has attracted a good number of young doctors. Gastroenterology is likely to grow in size and quality in Bangladesh.
BRIEF COMMUNICATION: A rapid and simple method to quantify Helicobacter pylori adhesion to human gastric MKN‐28 cells
Authors: HAYASHI SHUNJI , SUGIYAMA TOSHIRO , YACHI AKIRA , YOKOTA KENJI , HIRAI YOSHIKAZU , OGUMA KEIJI , FUJII NOBUHIRO
Published: March 2008

A rapid and simple method to quantitatively analyse Helicobacter pylori adhesion to human gastric epithelial cells was developed by using an enzyme‐linked immunosorbent assay. This method made it possible to quantitatively evaluate the adhesion activities of many different H. pylori strains at a time. Our studies indicate that this method is well suited for the quantitative analysis of H. pylori adhesion to gastric epithelial cells.
Use of spiral and non‐spiral computed tomography arterial portography in the detection of potentially malignant liver masses
Authors: YOUNG NOEL , SING TOM , WONG KAI PING , HOLLANDS MICHAEL , TAIT NOEL
Published: March 2008

The present study assesses the usefulness of computed tomography (CT) arterial portography (CTAP) in detecting and defining the number and anatomy of potentially malignant liver lesions. One hundred and one adults studied in 1993 and 1994 were retrospectively reviewed, including patients with primary or secondary tumours for possible resection and patients with non‐hepatic malignancies in whom the detection of liver metastases would preclude surgery. Twenty‐three patients underwent non‐spiral CT studies and 78 had studies on a spiral unit, with 22 of these having single phase and 56 having dual phase studies to overcome artefact problems. The relationship between lesion size and detection sensitivity is critical. On non‐spiral studies, the overall lesion detection sensitivity and positive predictive value was 69 and 90%, respectively. Detection sensitivity was 100 and 20% for lesions > 1 cm and < 1 cm, respectively. On single phase spiral CTAP the overall detection sensitivity and positive predictive value was 80 and 66%, respectively. Detection sensitivity for lesions > 1 cm and < 1 cm was 100 and 0%, respectively. On dual phase spiral CTAP the overall detection sensitivity and positive predictive value was 76 and 71%, respectively. For lesions > 1 cm and < 1 cm the sensitivity was 81 and 55%, respectively. Eighteen patients with non‐hepatic malignancies with unsuspected metastatic spread did not proceed to major surgery because of liver metastases detected on CTAP. Perfusion artefacts occurred in 30 and 64% of non‐spiral and of initial portal venous spiral CTAP studies, respectively. By using the double‐phase technique, these artefacts were substantially diminished. In conclusion, CTAP is a valuable tool for assessing the presence, site and size of possible liver tumours and confers a benefit even when previous ultrasound and conventional CT have already been used. In addition, CTAP has a lower limit of useful resolution of approximately 1 cm. Perfusion artefacts can be reduced by a dual phase protocol.
REVIEW: Nonalcoholic steatohepatitis
Authors: LUDWIG JURGEN , McGILL DOUGLAS B , LINDOR KEITH D
Published: March 2008

Nonalcoholic steatohepatitis (NASH) is a reasonably well‐defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non‐progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non‐progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.
Viral hepatitis in Japan: Update
Authors: NISHIOKA MIKIO , MORSHED SYED AHMED
Published: March 2008

Viral hepatitis is defined as a hepatitis virus infection in which hepatic inflammation and necrosis lead to a characteristic feature. It is caused by at least five viral agents with specific epidemio‐logical attributes and distinctive immunoserologic findings. The well‐characterized forms are hepatitis A, B, C, D and E viruses. Recent status and the current progress of viral hepatitis in Japan are discussed in the present article.
Tropical calcific pancreatitis and fibrocalculus pancreatic diabetes in Bangladesh
Authors: KHAN AK AZAD , ALI L
Published: March 2008

The relationship between tropical calcific pancreatitis (TCP) and fibrocalculus pancreatic diabetes (FCPD) is still unclear. The clinical, biochemical and radiological data of age‐matched TCP and FCPD subjects have been briefly discussed in the present review. Fibrocalculus pancreatic diabetes patients present with a significantly lower BMI compared with TCP patients. Analysis of the family history reveals that some kind of environmental factors seem to play a predominant role in the development of diabetes in FCPD patients, although these factors remain to be identified. Both TCP and FCPD patients predominantly come from a rural background. Fasting and 2 h blood glucose values as well as fructosamine levels in FCPD patients are approximately four‐times higher than those of TCP patients. Measurements of early renal haemodynamic and microvascular changes (glomerular filtration rate, kidney size, microalbuminuria and microtransferrinuria) indicate an early renal involvement in FCPD patients. Tropical calcific pancreatitis subjects have approximately twice as high fasting C‐peptide values compared with FCPD patients. Findings of single stranded DNA measurements suggest the involvement of oxidative damage in FCPD patients. Ketosis resistance is the most conspicuous clinical feature in the FCPD group and this relative absence of ketosis is probably due to a defect in the ketone body synthesis pathway and/or in the regulation of counterbalancing hormones. Endoscopic retrograde pancreatography findings of TCP and FCPD patients suggest that FCPD should not be considered only as a form of secondary diabetes consequent to generalized pancreatic damage in TCP.
Intestinal‐type tumour in resected gastric remnant cancer
Authors: LO SU‐SHUN , TSAY SHYH‐HAW , WU CHEW‐WUN , HSIEH MAO‐CHIH , LI ANNA FEN‐YAU , LUI WING‐YIU
Published: March 2008

Lauren's intestinal type of gastric cancer was proposed to be dependent on long‐term environmental factors and is always preceded by chronic premalignant change. A cohort study was performed and demonstrated an increased cancer risk of gastric remnant after gastric surgery for benign disease. It is generally believed that after gastrectomy the residual stomach has an environmental change and, thus, enters a neoplastic process. Based on the carcinogenic theory of intestinal‐type tumour, it would be of interest to know whether the intestinal‐type tumour is more common in gastric remnant cancer. Forty patients with gastric remnant cancer had gastrectomy in the Veterans General Hospital‐Taipei. Another 683 patients with primary gastric carcinoma underwent resection and were used as controls. The clinical characteristics, tumour stage and intestinal‐type tumour were analysed in gastric remnant cancer and were compared with the various portions of primary gastric carcinoma. Although the overall distribution of intestinal‐type carcinoma in gastric remnant (45%) was no different to that of any other portion of stomach cancer, intestinal‐type carcinoma was more common in the early stage of gastric remnant (73%) and distal stomach (73%), but not in the proximal stomach (50%), which was supposed to have the same characteristics as the gastric remnant because of identical anatomic location. More than expected, intestinal‐type carcinoma in early gastric remnant cancer together with a long incubation interval between primary surgery and later tumour occurrence were compatible with the theory of carcinogenesis of intestinal‐type carcinoma.
Liver transplantation for hepatitis C‐associated cirrhosis in a single Australian centre: Referral patterns and transplant outcomes
Authors: LEVY MT , CHEN JJ , McGUINNESS PH , KOOREY D , SHEIL AGR , McCAUGHAN GW
Published: March 2008

During the study period, 63 patients with hepatitis C virus (HCV) cirrhosis were referred to our unit for liver transplantation. All cases referred and transplanted were retrospectively examined. Eighty‐six per cent of referred patients were male, 35% consumed alcohol in the harmful hazardous range, 13% were infected with hepatitis B and 7% had hepatocellular carcinoma. Patients with sporadic infection were more likely to be born outside Australia and were an average of 10 years older than those with HCV acquired via intravenous drug use (P< 0.001). However, patients were an average of 12 years younger at referral if they consumed harmful amounts of alcohol than if they abstained (P = 0.002). We examined the impact of HCV on the outcome of 28 patients who underwent liver transplantation (mean follow up 25 months; range 3–76 months). The use of OKT3, HCV genotype and hepatitis B status were examined for their effect on HCV‐related graft dysfunction. Three year survival was 84%, equivalent to a control group. Chronic HCV‐related graft dysfunction occurred in 15 (56%) patients, of whom 10 had an asymptomatic elevation in serum amino transferase, two had cholestatic hepatitis and three had severe hepatitis C that progressed onto chronic rejection. Hepatitis C virus genotype 1b tended to be associated with HCV graft dysfunction (5/6 type 1b vs 10/16 in non‐type 1b). In conclusion, HCV is an increasingly common‐indication for liver transplantation. Alcohol and hepatitis B were frequently occurring cofactors in the referral cohort. Most patients referred were male, although the reason why is not clear. Transplantation offers a good medium‐term outcome, despite the high incidence of HCV‐associated graft dysfunction.
Earlier loss of hepatitis C virus RNA in interferon therapy can predict a long‐term response in chronic hepatitis C
Authors: KAKUMU SHINICHI , AIYAMA TOSHIYUKI , OKUMURA AKIHIKO , IWATA KAZUO , ISHIKAWA TETSUYA , YOSHIOKA KENTARO
Published: March 2008

To distinguish responders from non‐responders early in interferon (IFN) treatment would be beneficial in patients with chronic hepatitis C. Those patients unlikely to respond would be spared the cost and hazard of prolonged treatment. Forty‐three chronic hepatitis C patients who had received IFN‐α therapy (6–9 MU; six times weekly for 2 weeks followed by thrice weekly for 22 additional weeks) were randomly enrolled into the present study. Serially obtained sera were retrospectively tested for HCV‐RNA by reverse transcription‐polymerase chain reaction (AmplicorTM HCV) with a low limit detection of approximately 102 copies/mL. Genotypes were determined by type‐specific primers. Sixteen subjects were defined as sustained responders (SR), who showed sustained loss of viraemia with normalized alanine aminotransferase values for at least 6 months of follow‐up after completion of therapy. The other 27 subjects were non‐responders (NR), whose viraemia persisted during follow‐up. Pretreatment serum HCV‐RNA levels (P< 0.0001) and the genotype (P<0.01) were significant predictors for sustained response to IFN therapy. Hepatitis C virus RNA was detectable in only one (6%) SR and in 23 (85%) NR at the second week of therapy (P< 0.0001) and was detected in none of the SR subjects and in 18 (67%) NR at the fourth week of therapy (P< 0.0001). Pretreatment viral load was correlated with the time until loss of viraemia. Multivariate analysis revealed that loss of viraemia at the second week of therapy was the strongest predictor for a long‐term response, followed by the initial viral load and loss of viraemia at the fourth week of therapy. These findings suggest that it is possible to predict a long‐term response to IFN as early as at the second and fourth weeks after the start of therapy by identifying the presence or absence of HCV‐RNA with a sensitive assay.
Helicobacter pylori induces an array of pro‐inflammatory cytokines in human gastric epithelial cells: Quantification of mRNA for interleukin‐8, ‐1α/β, granulocyte‐macrophage colony‐stimulating factor, monocyte chemoattractant protein‐1 and tumour necrosis factor‐α
Authors: JUNG HYUN CHAE , KIM JUNG MOGG , SONG IN SUNG , KIM CHUNG YONG
Published: March 2008

Despite the fact that Helicobacter pylori is known to be non‐invasive, mucosal infiltration of inflammatory cells have been observed in the gastric mucosa. The exact pathogenesis of such an inflammatory reaction has not been well defined. We explored the repertoire of cytokine genes expressed in human gastric epithelial cells in response to coculture with H. pylori. After gastric epithelial cells, SNU‐5 and KATO III, were infected with H. pylori, expression of several cytokine genes was assessed using quantitative reverse transcription polymerase chain reaction. Interleukin (IL)‐8, ‐1α and ‐1β mRNA were expressed in both gastric epithelial cells throughout the entire infection period. In SNU‐5, IL‐1α and IL‐8 mRNA were expressed at 1 h, reached a peak level at 4 h and then decreased. Interleukin‐1β mRNA was expressed less frequently than IL‐1α or IL‐8 mRNA. In SNU‐5 cells, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), monocyte chemoattractant protein‐1 (MCP‐1), and tumour necrosis factor‐α (TNF‐α) mRNA were expressed at 9h, but was not expressed in KATO III. Gene expression paralleled the amount of IL‐8 protein measured by enzyme‐linked immunoabsorbent assay (ELISA). Interleukin‐8 mRNA expression was not observed in KATO III cells infected with Campylobacter fetus ssp. fetus, Campylobacter jejuni or Escherichia coli. IL‐8 mRNA expression was increased not only in gastric epithelial cells but also in non‐gastric cells infected with H. pylori. These results suggest that an inflammatory reaction induced by H. pylori may be initially triggered by an array of pro‐inflammatery cytokines expressed by infected gastric epithelial cells.
Circulating antioxidants in ulcerative colitis and their relationship to disease severity and activity
Authors: RAMAKRISHNA BS , VARGHESE R , JAYAKUMAR S , MATHAN M , BALASUBRAMANIAN KA
Published: March 2008

Oxygen free radicals produced by neutrophils are important in the pathogenesis of mucosal damage in ulcerative colitis. Vitamin A, vitamin E and cysteine in the plasma can scavenge free radicals. In the present study, plasma levels of vitamin A, vitamin E, cysteine, cystine and protein‐bound cysteine were measured in active ulcerative colitis before and immediately after treatment of the active disease, and correlated with disease severity, extent and activity. Plasma vitamin A and cysteine were significantly reduced in active ulcerative colitis compared with controls. Levels of vitamin E, cystine and protein‐bound cysteine were not significantly altered in active ulcerative colitis. Vitamin A and cysteine concentrations returned to normal levels (P< 0.05) within 2 weeks of treating active colitis. There were significant negative correlations between clinical severity and the plasma concentrations of vitamin A and cysteine. Plasma cysteine levels also correlated inversely to disease extent. Depletion of the circulating antioxidants, vitamin A and cysteine, in active ulcerative colitis is likely to be important in the pathophysiology of the disease.
Hepatitis C virus RNA present in saliva but absent in breast‐milk of the hepatitis C carrier mother
Authors: KAGE MASAYOSHI , OGASAWARA SACHIKO , KOSAI KEN‐ICHIRO , NAKASHIMA EISUKE , SHIMAMATSU KAZUHIDE , KOJIRO MASAMICHI , KIMURA AKIHIKO , FUJISAWA TAKUJI , MATSUKUMA YOSHINORI , ITO YUJI , KONDO SHIGENOBU , KAWANO KATSUICHI , SATA MICHIO
Published: March 2008

In order to examine whether saliva and breast‐milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast‐milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1‐ to 3‐month intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast‐milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast‐milk is not likely to be a source of mother‐to‐child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.
Review: Molecular epidemiology of hepatitis C virus
Authors: SMITH DONALD B , SIMMONDS PETER
Published: March 2008

Molecular techniques have been used to investigate the epidemiology of hepatitis C virus (HCV) at several different levels. At a global level, the time of divergence of the diverse HCV genotypes isolated from different geographical regions has been estimated from the rate of divergence observed among a cohort of individuals infected from a common source. Estimates of more than 300 years for virus subtypes and more than 500–2000 years for virus types are consistent with their current geographical distributions. Analysis of virus sequences has also provided evidence for a common source of infection in several large‐scale outbreaks of HCV infection, although where there is evidence that the implicated source contains more than one variant it may be difficult to distinguish individuals infected by different sources. Finally, sequence analysis has been used to investigate the vertical or horizontal transmission of HCV between pairs of individuals. The hypervariable region of the E2 gene is the most informative region to study if samples are available soon after the transmission event, but evidence for more distant events can still be obtained from analysis of genes such as NS5b and E1. Interpretation of some studies is complicated by the conservation of the gene region studied, or by the failure to make comparisons with sequences from epidemiologically unrelated viruses.
Visual and auditory evoked responses in acute severe hepatitis
Authors: SAWHNEY IMS , VERMA PK , DHIMAN RK , CHOPRA JS , SHARMA A , CHAWLA YK , DILAWARI JB
Published: March 2008

Evoked responses have not been studied in patients with acute severe hepatitis (ASH) with or without hepatic encephalopathy. This prospective study was undertaken to find out diagnostic as well as prognostic value of visual evoked responses (VER), and brain stem auditory evoked responses (BAER) in patients with ASH with or without encephalopathy. Visual evoked responses and BAER were studied in 20 patients (14 males and six females) with ASH. The patients were diagnosed as having severe hepatitis if acute hepatitis was associated with raised serum bilirubin and serum transaminases, and if they had a prothrombin time index of < 50%. After a detailed neuropsychiatric examination of each patient, the study sample was divided into two groups of 10 patients: ASH without encephalopathy (ASH‐WOE), and ASH with encephalopathy (fulminant hepatic failure, FHF). The median P100 latencies of FHF patients were significantly increased compared with controls and patients in the ASH‐WOE group. Abnormal P100 latencies, exceeding 95th percentile values of the controls, were present in one patient in the ASH‐WOE group and six patients in the FHF group. The median interpeak latencies I‐III, III‐V and I‐V were significantly prolonged in the FHF group. Interpeak latencies III‐V were also increased significantly in patients in the ASH‐WOE group. While abnormal BAER were seen frequently in both groups, VER abnormalities were largely confined to patients in the FHF group. In the FHF group, six out of 10 patients survived and exhibited clinical improvement in the status of hepatic encephalopathy. Evoked responses were repeated after 2–3 weeks of recovery in these patients and VER abnormalities showed a tendency to normalize, thereby suggesting a prognostic implication. The incidence of abnormal VER in hepatic encephalopathy complicating ASH far exceeded that of abnormal BAER. Markedly prolonged P100 latencies in FHF patients indicate poor prognosis.
Molecular biology of hepatitis D virus: Research and potential for application
Authors: CHEN PEI‐JER , WU HUI‐LIN , WANG CHUAN‐JEN , CHIA JU‐HSIN , CHEN DING‐SHINN
Published: March 2008

Superinfection by hepatitis D virus (HDV) leads to acute hepatitis and causes progression to liver cirrhosis in a significant proportion of hepatitis B surface antigen (HBsAg) carriers. Current regimens (interferon) to treat hepatitis D patients has only transient but no lasting effects. New approaches are, therefore, warranted. Recently, several laboratory studies have discovered interesting properties of HDV that may become targets for antiviral chemicals. Viral replication requires the small hepatitis delta antigen (s‐HDAg). The s‐HDAg is a nuclear phosphoprotein. There is evidence indicating that phosphorylation is important for HDV replication. A second step of replication requires HDV‐RNA self‐cleavage and self‐ligation. Interestingly, one group of antibiotics, the aminoglycosides, exerts strong suppression effects on HDV ribozyme activities. In the following stage of viral assembly, two post‐translational modifications, namely isoprenylation of large HDAg and glycosylation of HBsAg are involved. Agents capable of blocking the two modifications should reduce viral production. These four possible targets are reviewed. For prevention, effective vaccines are not yet available. Two novel approaches are discussed. The first demonstrates the immunogenicity of a nucleic acid vaccine in mice. The second approach assembled an empty HDV particle in yeast. Advances on such laboratory investigations may provide new methods for the control of hepatitis D in the future.
Novel hepatitis agents: The significance of clinical and experimental studies. An overview
Authors: KRAWCZYNSKI K
Published: March 2008

A new virus with genomic organization similar to that of the family Flaviviridae was identified in patients with viral hepatitis and designated hepatitis G virus (HGV) or hepatitis GB virus C (GBV‐C). HGV/GBV‐C can be transmitted by blood and results in persistent infection, as shown in patients with posttransfusion non‐A, non‐B hepatitis, in transfusion recipients, and in donors of blood received by HGV‐positive patients. The parenteral route of transmission of HGV/GBV‐C infection was confirmed in experimentally infected chimpanzees. Epidemiologic studies of sporadic, community‐acquired viral hepatitis have not indicated an association between HGV/GBV‐C and acute non A‐E hepatitis. Thus, the disease association of this new virus remains unconfirmed and its role in the etiology of acute and chronic hepatitis is unclear. The experimental model of HGV/GBV‐C infection may define the biology of the virus replication.
T cell mechanisms in the immunopathogenesis of viral hepatitis B and C
Authors: TSAI SL , HUANG SN
Published: March 2008

Considerable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B and C. Both CD4+ and CD8+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and paediatric patients, and are more vigorous in patients with acute self‐limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also had a significant CD4+ T cell response to hepatitis C virus (HCV) antigens. These responses are also vigorous in acute hepatitis C with recovery than in those cases that evolve to chronic hepatitis C. In terms of human leucocyte antigen (HLA) class I‐restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated as the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within both HBsAg and HBcAg can be detected by sensitizing target cells with synthetic peptides. Similar to hepatitis B virus (HBV) infection, multi‐specific, HCV‐specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C are not yet clarified.
Epidemiological characteristics and risk factors of hepatocellular carcinoma
Authors: CHEN CHIEN‐JEN , YU MING‐WHEI , LIAW YUN‐FAN
Published: March 2008

Hepatocellular carcinoma (HCC) is one of the major cancers in the world. There is a striking variation in HCC incidence rates between various countries, with a highest‐to‐lowest ratio of 112.5 for males and 54.7 for females. The high‐risk populations are clustered in sub‐Saharan Africa and eastern Asia. The male‐to‐female ratio for HCC ranges from < 1 to 6.4 and mostly from 2 to 4. There exist significant variations in the incidence of HCC among different ethnic groups living in the same area and among migrants of the same ethnic groups living in different areas. The age curves of HCC are significantly different in various countries, suggesting variability in exposure to risk factors. Chronic carriers of hepatitis B and C viruses (HBV and HCV, respectively) have an increased risk of HCC. The relative and attributable HCC risk of HBV and HCV carrier status varies in different countries. There exists a synergistic interaction on HCC between the two viruses. Aflatoxin exposure, cigarette smoking, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload and the use of oral contraceptives and anabolic steroids have been documented as HCC risk factors. Recent molecular epidemiological studies have shown that low serum retinol levels as well as elevated serum levels of testosterone, neu oncoprotein and aflatoxin B1‐albumin adduct are associated with an increased HCC risk. There is a synergistic interaction on HCC between chronic HBV infection and aflatoxin exposure. Familial aggregation of HCC exists and a major susceptibility gene of HCC has been hypothesized. Patients of some genetic diseases are at an increased risk of HCC. The genetic polymorphisms of cytochrome P450 2E1 and 2D6 and arylamine N‐acetyltransferase 2 are associated with the development of HCC. A doseresponse relationship between aflatoxin exposure and HCC has been observed among chronic HBV carriers who have null genotypes of glutathione S‐transferase M1 or T1, but not among those who have non‐null genotypes. Human hepatocarcinogenesis is a multistage process with the involvement of a multifactorial aetiology. Gene‐environment interactions are involved in the development of HCC in humans.
Hepatocellular carcinoma: Clinicopathological aspects
Authors: OKUDA KUNIO
Published: March 2008

The histopathology and clinical picture of hepatocellular carcinoma (HCC) varies between individual patients and regions. These variations are perhaps due to differences in the genetic alterations that precede hepatocarcinogenesis. In this study, the clinicopathological features of HCC were compared between southern African blacks and Japanese, indicating large differences in the frequency of underlying cirrhosis, grade of cancer cell differentiation and clinical course. Intra‐abdominal bleeding and febrile, rapidly progressive HCC are more common among blacks. Such a difference is accounted for, in part, by frequent encapsulation of the tumour which is well differentiated, and grows slowly in an expanding fashion in Japan. Encapsulated HCC was not seen among the black patients studied. Other distinct clinicopathological types discussed in this paper include diffuse‐type HCC which is usually caused by multiple portal spread occurring almost simultaneously; the clinical course is fulminant. Sclerosing carcinoma is frequently associated with hypercalcaemia in the United States, but not in Japan. Fibrolamellar carcinoma is nearly non‐existent in Asia, whereas it is common among young adults in the West. Its prognosis is generally better than ordinary HCC. Hepatocellular carcinoma has a strong propensity to invade vessel and duct systems. Portal invasion does not produce distinct clinical signs although it may aggravate portal hypertension. Patients with tumour occlusion in the major portal vein may give rise to ischaemic hepatitis when blood pressure drops suddenly in the preterminal stage. Liver parenchyma develops submassive necrosis and clinically there is an acute rise in alanine aminotransferase (ALT). Invasion into a major hepatic vein and the inferior vena cava also occurs, but less frequently compared with portal invasion. The patient can live even with a tumour thrombus in the atrium crossing the tricuspid valves. Intraductal invasion causes acute jaundice as well as an occasional haemobilia with pain. We recently found that a distinct pathological type called ‘extrahepatic growth’ or ‘pedunculated HCC’ develops as a result of fusion of right‐sided adrenal metastasis of HCC and the liver, perhaps through the ‘adreno‐hepatic fusion’ which is rather common in cirrhotic livers.
Partial hepatic resection for hepatocellular carcinoma
Authors: CHEN MIIN‐FU , JENG LONG‐BIN
Published: March 2008

This review summarizes the efficacy of the most common therapeutic option for hepatocellular carcinoma (HCC), partial hepatic resection, taking into account not only its antitumoural effect, but also its consequences on survival. Partial hepatic resection results in 5 year survival rates as high as 45% in more favourable subgroups having: small tumours, well‐differentiated tumours, unifocal tumours, a lack of vascular invasions, an absence of cirrhosis, and the nbrolamellar variant. Resection has been limited primarily by low resectability rates and recurrent disease. However, surgical resection in the form of partial hepatectomy is the preferred treatment for HCC. The early detection of tumours by screening high‐risk populations is crucial. During the 12 year period between 1983 and 1994, hepatic resections were carried out in 382 patients with HCC. One hundred and fifty‐three (40%) had HCC smaller than 5 cm in diameter. There were 294 male and 88 female patients, with an average age of 52.3 years. Among them, 45% had liver cirrhosis and 73% were positive for hepatitis B surface antigen. Two hundred and eighteen (57%) were positive for hepatitis C virus circulating antibodies (since 1991). Operative mortality was 3.9%. The overall survival rates at 1, 3 and 5 years were 71, 52 and 46%, respectively. Sex, cirrhosis, Child's staging, surgical procedure, blood loss, pathological pattern, presence of capsule, surgical margin and DNA ploidy appeared to be factors not related to prognosis. However, α‐fetoprotein level, size (whether less than or greater than 5 cm), and vascular invasion were factors which significantly affect survival.
Current therapeutic trends in therapy for chronic viral hepatitis
Authors: LIAW YUN‐FAN
Published: March 2008

Hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV) are associated with clinically significant chronic infection that may lead to the development of cirrhosis or even hepatocellular carcinoma (HCC). Intervention at the earliest possible stage is needed to prevent such untoward sequelae. Currently, interferon (IFN) is the only approved and widely used agent for the treatment of these infections, including in HBV patients with precore mutant hepatitis or decompensated cirrhosis, but its efficacy is far from satisfactory. Corticosteroid priming has been shown to increase the efficacy of IFN therapy in HBV patients with low abnormal serum transaminase levels, but only a few responders will clear serum hepatitis Bs antigen (HBsAg). Ongoing randomized controlled trials of thymosin α1, lamivudine and famcyclovir have demonstrated encouraging preliminary results. Therapeutic vaccines, such as polypeptides with human leucocyte antigen (HLA)‐specific hepatitis B core antigen (HBcAg) epitopes, are under phase II/III clinical trial. For HDV infection, the use of IFN in the early phase of acute superinfection tends to prevent chronic progression. For HCV infection, IFN used at higher doses for a longer period of time is associated with a higher sustained response, but overall it is still not satisfactory. The combined use of ribavirin or corticosteroid priming may improve the effect of IFN therapy by enhancing the durability of the response. Interferon in the acute phase of HCV infection may also prevent chronic progression. There is evidence to suggest that IFN therapy, when associated with response, tends to reduce the risk of cirrhosis or HCC and prolongs survival. There is no doubt that satisfactory treatment of chronic viral infection will require more effective agents and demand optimal treatment strategies, many of which are yet to be found.
Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma
Authors: SUNG JUEI‐LOW
Published: March 2008

In Taiwan, cirrhosis and hepatocellular carcinoma (HCC) have been common in medical practice since the 1960s. In 1969, Taiwan was shown to be a hyperendemic area of hepatitis B virus (HBV) infection with a high rate of hepatitis B surface antigen (HBsAg) positivity, 19% of the population being infected before the fourth decade of life. There is evidence indicating that more than 80% of chronic hepatitis, cirrhosis and HCC are the sequelae of chronic HBV infection. In 1984, after 3 years of preparation, a programme to control cirrhosis and HCC began. All neonates born to HBsAg+ mothers were given Pasteur plasma‐derived vaccine 5 μg i.m. at 1, 5 and 9 weeks with a booster at 12 months. In 1986, all neonates were included in this programme. In addition, beginning in 1987, all non‐vaccinated preschool children were also immunized and susceptible medical personnel and people from HBsAg+ households were recommended to receive the vaccine. Using data obtained from the 7‐year evaluation study on the efficacy of this vaccine and some historical data, the HBsAg positivity rate in people born in the first few years after 1986 was estimated to be 2.6%. This rate is expected to decrease to 0.2% in those born after around 1990. In July 1992, an anti‐hepatitis C virus (HCV) test was included in blood donor screening tests. This was followed by a decrease in the incidence of post‐transfusion hepatitis (PTH) from 13 to 2.5% and there have been no anti‐HCV+ PTH cases since. However, without immunization, the prevalence of HBsAg decreased among children in Taipei in 1989. This coincided with the widespread use of disposable syringes and needles and an improvement in the sterilization of medical instruments. Therefore, it is likely that HCV infection may also decrease as a result of these practices. Through the use of immunization and improved medical procedures, chronic hepatitis, cirrhosis and HCC may decrease in Taiwan by around 95%.
Negative strand of hepatitis C virus RNA in the liver of patients with chronic hepatitis C after interferon treatment
Authors: TOMIMATSU MASAHIKO , ENDOU HITOSHI , TAKAHASHI HARUKI , IGA DAIJIRO , KATO YOSHIKAZU , TAMAI NORIO , NAKAJIMA HIROKO , OKANO AKIRA , MORI HARUKI , HISATOMI HISASHI
Published: March 2008

In patients receiving interferon therapy for chronic hepatitis C, serum hepatitis C virus (HCV) RNA often reverts from an undetectable to a detectable form after completion of treatment. Detection of the negative strand of HCV‐RNA in liver tissue is regarded as an index of viral proliferation. Therefore, we investigated changes in the hepatic negative‐strand HCV‐RNA following interferon therapy to determine whether this parameter could predict the long‐term response to treatment. The subjects of this study were 27 patients with chronic active hepatitis C. Serum positive‐strand and hepatic tissue negative‐strand HCV‐RNA were detected using polymerase chain reaction. At the completion of interferon treatment, serum HCV‐RNA was not detected in 21 patients. One year following treatment it remained undetectable in 14 of these patients but it had reverted to a detectable form in seven. The 14 patients in whom hepatic negative‐strand RNA was not detected between 2 weeks and 12 months after treatment, had not relapsed after another year. In the 13 remaining patients, negative‐strand RNA was found in liver tissue and serum RNA either reverted to a detectable form or remained detectable throughout. From these findings, we conclude that the detection of negative‐strand HCV‐RNA in liver tissue 2 weeks after the completion of interferon therapy is useful for predicting the long‐term effect of therapy.
Abnormality in fatty acid composition of gastric mucosal phospholipids in patients with liver cirrhosis and its correction with a polyunsaturated fatty acid‐enriched soft oil capsule
Authors: MIYAMOTO AYUMU , WAKABAYASHI HIROYUKI , WATANABE AKIHARU
Published: March 2008

The abnormal composition of the fatty acids in gastric mucosal phospholipids was examined in 11 patients with non‐alcoholic liver cirrhosis accompanied by gastritis and in 10 healthy subjects without liver disease and gastritis. The cases positive for serum anti‐Helicobacter pylori immunoglobulin G antibody were excluded. The arachidonic acid (AA, C20:4n‐6) contents of the two main components of phospholipid, the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions, in gastric biopsy specimens were significantly lower in the cirrhosis group, although PC and PE contents in gastric biopsy specimens were not altered. In the cirrhosis group, AA contents of the PC fractions in gastric biopsy specimens were significantly correlated with AA contents of plasma PC fractions and serum albumin levels. Soft oil capsules containing polyunsaturated fatty acid (PUFA) such as AA, eicosapentanoic acid (EPA, C20:5n‐3) and docosahexanoic acid (DHA, C20:6n‐3) were administered after each meal daily for 4 weeks to six cirrhotic patients and four control subjects, who were randomly selected from the patients and control subjects. After administration of PUFA‐enriched oil capsules, gastric mucosal AA contents of PC and PE fractions were significantly improved almost to the control levels. In three cirrhotic patients with severe or mild gastritis whose gastric mucosal lesions were endoscopically shown to have responded to PUFA‐enriched oil capsules, AA contents of plasma PC and PE fractions before administration were much lower than in the remaining three cirrhotics that did not respond to the PUFA‐enriched oil capsules, but significantly improved to the control levels after administration of oil capsules. The results demonstrate that administration of PUFA‐enriched soft oil capsules increased AA contents of the phospholipids in gastric mucosa and thus improved gastric mucosal lesions endoscopically in cirrhotic patients with gastritis.
Virulence‐associated genes as markers of strain diversity in Helicobacter pylori infection
Authors: ITO AKIRA , FUJIOKA TOSHIO , KODAMA KAORU , NISHIZONO AKIRA , NASU MASARU
Published: March 2008

To establish a marker of strain diversity of Helicobacter pylori, a genetic examination was performed based on the detection rates by PCR of cagA and vacA, which are known to be virulence‐associated genes. The test strains were obtained from 70 patients suffering from gastric ulcer (GU), 82 patients with duodenal ulcer (DU) and 48 patients with gastritis (GS). Fragments located in the three different regions of vacA were amplified; V1 being the upstream portion, V2 the mid‐portion and V3 the downstream portion. For cagA, the detection rates were 70% for GU, 79% for DU and 50% for GS, showing a significantly higher rate for DU than for GS (P= 0.0005). With V1, the detection rates were 90% for GU, 90% for DU and 69% for GS, giving a significantly higher rate for GU than for GS (P= 0.0036) and also giving a significantly higher rate for DU than for GS (P= 0.0019). With V2, the detection rates were 60% for GU, 70% for DU and 44% for GS, giving a significantly higher rate for DU than for GS (P= 0.0024). The differences in vacA gene polymorphism were closely related to the evidence of gastroduodenal ulcers in H. pylori infection. Furthermore, the detection rates of cagA and polymorphisms of vacA by PCR could be used as markers of strain diversity in H. pylori‐induced gastroduodenal ulcer.
REVIEW: The surgical management of ulcerative colitis
Authors: FRIZELLE FA , BURT MJ
Published: March 2008

The treatment of ulcerative colitis requires careful review of the medical and surgical options. The surgical procedure of choice is proctocolectomy with ileal pouch‐anal anastomosis. This procedure removes the diseased mucosa, effectively curing the disease whilst maintaining the normal route of defecation and continence. Other surgical options that may be considered in selected patients include proctocolectomy with either a Brooke ileostomy or a Kock pouch, and abdominal colectomy with ileorectal anastomosis. The choice of operation requires consideration of the advantages and disadvantages of a particular procedure and must be tailored to an individual patient's needs and circumstances.
Thiolmethyltransferase activity in the human colonic mucosa: Implications for ulcerative colitis
Authors: MOORE JAMES WE , BABIDGE WENDY J , MILLARD SUE H , ROEDIGER WILLIAM EW
Published: March 2008

Ulcerative colitis is associated with a selective reduction of n‐butyrate oxidation by the colonic epithelial cells although the reason for this has been unclear. Colonic epithelial cell n‐butyrate oxidation can be inhibited in vitro by incubation with sulphide but the role of mucosal detoxification of sulphide in the metabolic welfare of the colonic mucosa has not been examined. This study aimed to assess the role mucosal detoxification of sulphide by thiolmethyltransferase (TMT)‐mediated methylation may play in protecting the healthy colonic mucosa from the adverse effects of luminal sulphide. Colonic epithelial cell suspensions from healthy human proximal (n= 9) and distal colon (n= 10) were incubated in the presence of 14C‐labelled n‐butyrate (5 mmol/L) alone, butyrate plus sodium hydrogen sulphide (NaHS) (1.5 mmol/L), or butyrate plus NaHS plus S‐adenosyl‐methionine 1,4 butane disulphonate (SAMe) (5 mmol/L). Study end points were metabolic performance (14CO2 production) and mucosal TMT activity. Incubation with NaHS induced a significant inhibition of 14CO2 production compared with control incubations (P < 0.001) which was similar for proximal and distal colonic cell suspensions. S‐adenosyl‐methionine 1,4 butane disulphonate reversed this effect completely in proximal but not in distal cell incubations, suggesting a greater susceptibility of the distal colon to the sulphide effect. Although median whole mucosal TMT values did not differ between proximal and distal colonic mucosa, a non‐normal distribution of distal TMT values was observed. However, neither the degree of sulphide inhibition of control 14CO2 production nor the degree to which SAMe reversed this inhibition correlated with whole mucosal TMT activity. The study concluded that regional variation exists in TMT activity in the human colon but whilst methylation appears to protect colonic epithelial cells against sulphide‐induced inhibition of n‐butyrate oxidation, this cannot be directly correlated with mucosal TMT activity.
Helicobacter pylori: From art to a science
Authors: HUNT RH , LAM SK
Published: March 2008

Helicobacter pylori infection is widely prevalent especially in developing countries. Increasing knowledge of the pathophysiology associated with H. pylori is leading to an understanding of the mechanisms of mucosal inflammation and gastritis and how this leads to peptic ulcer disease, gastric mucosal associated lymphoid tissues (MALT), lymphoma and gastric cancer. More accurate diagnostic testing for the infection is now possible with both endoscopic and non‐endoscopic tests to identify patients most appropriate for eradication therapy. Modern treatments tend to overcome the problems of metronidazole resistance and compliance seen with two week bismuth triple therapy and widely studied is a proton pump inhibitor given with clarithromycin and amoxicillin or metronidazole for one week. These achieve amongst the highest eradication rates and have also been shown to be cost effective. This paper reviews these recent advances and addresses areas of clinical interest and future directions.