Showing papers in "Journal of Gastroenterology and Hepatology in 2000"

Chronic hepatitis B virus infection in Asian countries

Abstract: Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.

Reactive oxygen and mechanisms of inflammatory liver injury

Abstract: Reactive oxygen species (ROS) are important cytotoxic and signalling mediators in the pathophysiology of inflammatory liver diseases. They can be generated by resident and infiltrating phagocytes and/or intracellularly in every liver cell type after stimulation with cytokines. Although ROS are able to cause cell destruction by massive lipid peroxidation, in most cases, ROS are more likely to modulate signal transduction pathways by affecting redox-sensitive enzymes, organelles (e.g. mitochondria) and transcription factors. Thus, ROS can directly induce and/or regulate apoptotic and necrotic cell death. In addition, ROS can have indirect effects on the pathophysiology by supporting protease activity through inactivation of antiproteases and by modulating the formation of inflammatory mediators and adhesion molecules. Many of the effects of ROS may occur simultaneously or sequentially in the pathophysiology. Although mainly described in this review as detrimental, ROS are essential for host-defence functions of phagocytes and can modulate the formation of mediators involved in regulating sinusoidal blood flow and liver regeneration. Thus, continuous efforts are necessary to improve our understanding of the role of ROS in the pathophysiology of inflammatory liver diseases and to discover therapeutic interventions that selectively target the negative effects of reactive oxygen formation.

Hepatitis E: an overview and recent advances in clinical and laboratory research.

Abstract: Hepatitis E virus (HEV) is a non-enveloped RNA (7.5 kb) virus that is responsible for large epidemics of acute hepatitis and a proportion of sporadic hepatitis cases in southeast and central Asia, the Middle East, parts of Africa and Mexico. Hepatitis E virus infection spreads by the faecal-oral route (usually through contaminated water) and presents after an incubation period of 8-10 weeks with a clinical illness resembling other forms of acute viral hepatitis. Clinical attack rates are the highest among young adults. Asymptomatic and anicteric infections are known to occur. Chronic HEV infection is not observed. Although the mortality rate is usually low (0.07-0.6%), the illness may be particularly severe among pregnant women, with mortality rates reaching as high as 25%. Recent isolation of a swine virus resembling human HEV has opened the possibility of zoonotic HEV infection. Studies of pathogenetic events in humans and experimental animals reveal that viral excretion begins approximately 1 week prior to the onset of illness and persists for nearly 2 weks; viraemia can be detected during the late phase of the incubation period. Immunoglobulin M antibody to HEV (anti-HEV) appears early during clinical illness but disappears rapidly over a few months. Immunoglobulin G anti-HEV appears a few days later and persists for at least a few years. There is no specific treatment available for hepatitis E virus infection. Ensuring a clean drinking water supply remains the best preventive strategy. Recombinant vaccines are being developed that may be particularly useful for travellers to disease-endemic areas and for pregnant women.

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology

Abstract: Background and Aims: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including pro-collogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. Methods and Results: Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382 ± 31 vs 110 ± 9 μg/L respectively, P < 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179 ± 11 μg/L) compared with patients without fibrosis (62 ± 20 μg/L; P < 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R = 0.5421, P < 0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 μg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. Conclusions: Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis.

Epidemiology of hepatitis B virus infection in the Asia-Pacific region.

Abstract: There is a wide variation of hepatitis B virus (HBV) infection in the Asia-Pacific region. The prevalence of chronic HBV infection is lowest (<1%) in North America, Australia and New Zealand, 2-4% in Japan, 5-18% in China and highest (15-20%) in Taiwan as well as several other countries in South East Asia. Perinatal transmission is common in HBV-hyperendemic areas. Geographical clusters of horizontal HBV infection have been reported in both high- and low-risk countries. Common sources of infection, including iatrogenic and sexual transmission, have been implicated. Migrant studies indicate the importance of childhood environments in the determination of HBV infection. Rural urban and ethnic differences in the prevalence of HBV infection have also been reported. There has been a decrease in the prevalence of HBV infection after mass HBV vaccination programmes in some Asia-Pacific countries, which may be due to the intervention of possible transmission routes through the use of disposable syringes and needles, screening of HBV infection markers in blood banks, and prevention of high-risk tattooing, acupuncture, ear-piercing and sexual contact. A striking decrease in the incidence of HBV infection and hepatocellular carcinoma has been observed among children in Taiwan and other areas where mass vaccination programmes have been implemented.

Percutaneous endoscopic gastrostomy: a review of indications, complications and outcome

Abstract: Percutaneous endoscopic gastrostomy (PEG) was first described in 1980 as an effective method of feeding via the stomach in situations where oral intake is not possible. Its simplicity has led to its potential use in areas of dubious clinical benefit. Our unit has faced a major increase in referrals for PEG insertion over the last 2 years. For this reason we decided to audit our PEG insertion procedures with regard to indications, complications, outcome and follow up. We studied 168 patients who had an initial PEG insertion during the period 1 February 1996-31 January 1998. The medical records of these patients were reviewed with regard to the procedure, antibiotic use and complications. All patients (or carers or next of kin) were contacted by telephone to provide details regarding late complications and follow up. There were 87 females and 81 males (aged 16-98 years, median age 70 years). At 2 years, 67% were alive. The most frequent indication for PEG insertion was a neurological condition, the commonest being stroke. Most patients received either ticarcillin/clavulanic acid or cephazolin antibiotic prophylaxis before and after the procedure. In six patients (3.6%) infection at the PEG site required intravenous antibiotics. Four of these six patients did not have antibiotic prophylaxis. Only two deaths could be directly related to the procedure. Three died within 7 days of the procedure due to unrelated medical complications. Sixteen patients died within 1 month, the majority of these patients did not leave hospital. One-fifth of the patients (35/168) had their PEG removed due to the re-establishment of oral feeding, with median time of use, 4.3 months. It is a safe, effective feeding method in the elderly, but experience with case selection, the procedure and careful follow up remain essential. The use of prophylactic antibiotics resulted in few significant infections of the PEG site. Up to one-fifth of patients will require their PEG only for a short term.

Putative role of hepatitis B virus X protein in hepatocarcinogenesis: Effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways

Abstract: Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-induced malignant transformation is, however, incompletely understood. HBx, the protein encoded by the X open reading frame, is a transcriptional activator that has been implicated in hepatocarcinogenesis. HBx inhibits the function of the tumour suppressor protein p53 in what is thought to be an early event in hepatocyte transformation before the later accumulation of inactivating p53 point mutations. HBx inhibits apoptosis but also exerts pro-apoptotic effects. The effects of HBx on apoptosis may be important not only for the development of HCC but also for the establishment of HBV infection. Further implication of HBx in hepatocyte transformation has been the demonstration that it inhibits the repair of damaged hepatocyte DNA. This effect may be mediated by interaction with p53 or through binding to the damaged DNA binding protein (DDB), which plays an accessory role in nucleotide excision repair. In addition, HBx activates cell signalling cascades involving mitogen-activated protein kinase (MAPK) and Janus family tyrosine kinases (JAK)/signal transducer and activators of transcription (STAT) pathways. The implications of these modulating effects of HBx are not fully understood, but they are likely to have wide-ranging effects on hepatocyte proliferation, apoptosis and the regulation of cell growth checkpoints. The cellular functions ascribed to HBx are unusually diverse, and defining the biologically important role of HBx during HBV replication will go some way to understanding the sequelae of chronic HBV infection.

Apoptosis in the intestinal epithelium: Its relevance in normal and pathophysiological conditions

Abstract: Apoptosis is now recognized as an important process responsible for maintenance of the cellular balance between proliferation and death. Apoptosis is distinct from necrosis in that it is a programmed form of cell death and occurs without any accompanying inflammation. This form of cell death can be induced by a wide range of cellular signals, which leads to activation of cell death machinery within the cell and is characterized by distinct morphological changes. Apoptosis is especially relevant in the gastrointestinal tract, as the mammalian intestinal mucosa undergoes a process of continual cell turnover that is essential for maintenance of normal function. Cell proliferation is confined to the crypts, while differentiation occurs during a rapid, orderly migration up to the villus. The differentiated enterocytes, which make up the majority of the cells, then undergo a process of programmed cell death (apoptosis). Although apoptosis is essential for the maintenance of normal gut epithelial function, dysregulated apoptosis is seen in a number of pathological conditions in the gastrointestinal tract. The cellular mechanisms regulating this tightly regimented process have not been clearly defined and this topic represents an area of active investigation as delineation of this process will lead to a better understanding of normal gut mucosal growth.

Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma

Abstract: The natural course of perinatally acquired hepatitis B virus (HBV) infection has three phases. In the first 'immune tolerance phase', patients are HBeAg positive and have high serum levels of HBV DNA, but have no symptoms, normal ALT levels and minimal histological activity. The second 'immune clearance phase' usually occurs between 15 and 35 years of age, during which HBV replication declines, accompanied by increased serum ALT levels and inflammatory activity in the liver; HBeAg to anti-HBe seroconversion is then observed, frequently preceded by a flare of the ALT level. The average rate of spontaneous HBeAg seroconversion is 10% per year. In the third 'low-replicative phase', serum HBsAg persists, but HBeAg is no longer detectable and HBV DNA can only be detected by PCR assay. During this phase, patients are usually asymptomatic and liver disease is inactive; some patients, however, may progress to cirrhosis and hepatocellular carcinoma (HCC). The ultimate outcome of chronic HBV infection appears to depend on the duration and severity of liver injury during the immune clearance phase. About 2.1% of patients with chronic type B hepatitis develop cirrhosis each year. Patients who have a severe acute exacerbation complicated by subacute hepatic failure or who have recurrent episodes of acute exacerbations with bridging hepatic necrosis are more likely to develop cirrhosis. A significant proportion of those with HBsAg eventually develop HCC; they have a 100-fold increased risk of HCC relative to those without. The development of HCC, however, is closely related to the severity of the underlying liver disease. The annual incidence of HCC is only 0.1% in asymptomatic HBsAg individual, 1% in patients with chronic hepatitis B, but increases to 3-10% in patients with cirrhosis. Some anti-HBe-positive patients continue to have active liver disease and they should be tested for HBV DNA by hybridization assay to determine whether the disease results from replicative precore mutant HBV infection or other causes of liver disease, such as superinfection with HCV and HDV. A substantial number of apparently healthy HBV-infected individuals are first recognized when they present with episodes of acute hepatitis. About 30% of these cases could be attributed to other hepatotropic virus superinfection. Acute viral hepatitis in patients with concurrent HBV infection is associated with an increased risk of fulminant hepatic failure. Finally, HBsAg disappears from serum in about 1% of patients each year. HCV superinfection can enhance the termination of HBsAg positivity. HCV, however, replaces HBV as the dominant cause of chronic viral hepatitis. The outcome of HBV-infected persons with 'spontaneous' seroclearance of HBsAg is usually favourable, though progress to cirrhosis and HCC is still possible.

Incidence and prevalence of ulcerative colitis in the Songpa‐Kangdong District, Seoul, Korea, 1986–1997

Abstract: Background and Aims: Ulcerative colitis (UC) is regarded as a rare disease in developing countries, but accurate data are generally lacking. We performed the present study to evaluate the incidence and prevalence of UC in Korea. Methods: A retrospective study was performed from 1986 to 1997 in the Songpa-Kangdong district of Seoul, Korea. To recruit UC patients as completely as possible, multiple information sources including all medical facilities in the study area and three referral centres located nearby, but outside the study area were used. The incidence and prevalence rates were adjusted using the 1997 Korean population statistics. Results: During the study period, a total of 94 incident cases were identified, for an adjusted mean annual incidence rate of 0.68 per 100 000 inhabitants. On 31 December 1997, 91 patients with UC lived in the study area, giving an adjusted prevalence rate of 7.57 per 100 000 inhabitants. By using the Poisson regression analysis, the annual incidence rate increased significantly from 0.20 per 100 000 inhabitants in 1986–1988 to 1.23 per 100 000 inhabitants in 1995–1997 (P < 0.005). Patient age at diagnosis, the interval from onset of symptoms to diagnosis, and the disease extent at diagnosis were fairly constant throughout the study period. Conclusions: The incidence and prevalence of UC in our study area are still low compared with those of Western countries, but the incidence rate is steadily increasing.

Aspartate aminotransferase : alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis?

Abstract: Background:The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST : ALT ≥ 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST : ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. Methods: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST : ALT. Results: In 30 patients with cirrhosis, the mean AST : ALT (0.99 ± 0.06) was higher than in 123 patients without cirrhosis (0.60 ± 0.02; P < 0.001). A ratio ≥ 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. Conclusion: Although relatively insensitive, an AST : ALT ≥ 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients. © 2000 Blackwell Science Asia Pty Ltd

Portal‐systemic encephalopathy in non‐cirrhotic patients: Classification of clinical types, diagnosis and treatment

Abstract: Hepatic encephalopathy is suspected in non-cirrhotic cases of encephalopathy because the symptoms are accompanied by hyperammonaemia. However, the cause of the large portal-systemic shunt formation observed in these cases is not clear, as cirrhosis and portal hypertension are absent. The frequency of such cases reported in the literature is increasing with progress and spread of abdominal imaging diagnostic techniques. Some cases have been misdiagnosed as psychiatric diseases (dementia, depression and others) and consequently patients have been hospitalized in psychiatric institutions or geriatric facilities. Some paediatric cases have also been misdiagnosed. Therefore, the importance of accurate diagnosis of this disease should be strongly emphasized. Some paediatric cases have also been misdiagnosed. When psychoneurological symptoms are suggestive of hepatic encephalopathy but objective and subjective symptoms or abnormal values of liver function tests are not sufficiently indicative of liver cirrhosis, portal-systemic encephalopathy should be suspected. Abnormal angiograms of the portal vein, superior mesenteric vein or splenic vein are conclusive evidence of portal-systemic encephalopathy. Transrectal portal scintigraphy also provides information useful for detection of shunts and a quantitative estimation of shunt index. We classified the disease into five types based on whether the shunt is formed inside or outside the liver. Type I (intrahepatic type) designates cases in which shunts are located between the portal and systemic veins. Type II designates a type of intra/extrahepatic shunt that originates from the umbilical part of the portal vein and serpentines in the liver, then leaves the liver. Type III (extrahepatic type) occurs most frequently. Type IV (extrahepatic) is accompanied by shunts similar to those in type III, but hepatic pathology presents as idiopathic portal hypertension. Type V (extrahepatic) represents the congenital absence of the portal vein, where the superior mesenteric vein joins the intrahepatic inferior vena cava or the left renal vein. The prevalence of each type in our country was examined by a nationwide investigation. In addition to the conventional diet or drug treatments, obliteration by less invasive interventional radiology using a metallic coil and ethanol has recently been used more frequently than surgical occlusion of shunts. Shunt-preserving disconnection of portal and systemic circulation and partial splenic artery embolization are also performed. International investigation of the disease status and establishment of diagnostic and therapeutic methods for the disease are awaited and investigation of long-term prognosis after therapy is also necessary.

Branched-chain amino acids.

Abstract: The branched-chain amino acids (BCAA), isoleucine, leucine and valine, are unique in that they are principally metabolized extrahepatically in the skeletal muscle This observation led to the investigation of these nutrients in a number of clinical scenarios By far the most intensively studied applications for BCAA have been in patients with liver failure and/or patients in catabolic disease states However, the resulting studies have not demonstrated a clear clinical benefit for BCAA nutritional supplements In patients with liver failure, the BCAA did improve nitrogen retention and protein synthesis, but their effect on patient outcome was less clear Similarly, in critically ill septic patients, BCAA did not improve either survival or morbidity The BCAA are important nutrients, and it seems that any specific benefits associated with their use will be based upon a greater understanding of the underlying cellular biology Potential areas of further research may include the combination of BCAA supplements with other anabolic factors (eg growth hormone) in managing patients with catabolic disease states

Treatment of chronic liver diseases with traditional Chinese medicine

Abstract: Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and P urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN-alpha. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6%, and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2,000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV-related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer's and Chevallier's criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B.

Herbal hepatotoxicity: an expanding but poorly defined problem.

Abstract: Alternative therapies, including herbal remedies, are popular in the general population and even more so among patients with liver disease. The use of such products is now well established in western society and is no longer confined to traditional medicine practitioners in Asia, Africa and the Middle-East. Their perceived benefits remain generally unproven and concern about adverse effects is leading to closer scrutiny of these products. Herbal hepatotoxicity has been recognized for many years, but new agents are constantly being identified. The varied manifestations of liver injury include steatosis, acute and chronic hepatitis, hepatic fibrosis, zonal or diffuse hepatic necrosis, bile duct injury, veno-occlusive disease, acute liver failure requiring liver transplantation and carcinogenesis. Potential interactions between herbal medicines and conventional drugs may interfere with patient management. Concurrent use of such products is not often disclosed unless specifically sought after and can lead to perpetuation of the liver injury. The present review focuses on emerging herbal hepatotoxins, newer patterns of liver injury among the older agents and provides an updated tabulation of the adverse effects of major herbal hepatotoxins. Key issues of diagnosis and prevention of this growing problem are addressed. Continued public education, physician awareness and more stringent licensing are required to tackle this growing problem.

Effect of age and Helicobacter pylori infection on gastric acid secretion

Abstract: Background: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. Methods: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0–4. Results: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. Conclusions: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age. © 2000 Blackwell Science Asia Pty Ltd

Characterization of antibody responses against rectal mucosa-associated bacterial flora in patients with ulcerative colitis.

Abstract: Background: Previous reports on faecal microflora have demonstrated that the total number of aerobes and coliforms was increased in patients with ulcerative colitis (UC). Based on the hypothesis that the pathogenesis of UC may be closely associated with the mucosal microflora, we investigated alterations in the mucosa-associated microflora of UC patients. Methods and Results: The bacterial counts for both aerobes and anaerobes increased in UC patients. In particular, we detected the highest bacterial counts of Bacteroides vulgatus and these bacteria were isolated most frequently. In addition, we also investigated the serum antibody responses against the bacteria isolated from the affected mucosa by serum bacterial agglutination tests and immunoblotting. A high agglutination titre against B. vulgatus, Bacteroides fragilis, and Clostridium ramosum was detected in most UC patients, and the percentage of positive immunoreactivity was much higher in UC patients than in healthy controls. From the results of the immunoblotting, a unique antigenic determinant of B. vulgates (BV43-26), a 26-kDa protein from the outer membrane, was discovered. The serum immunoreactivity (immunoglobulin (Ig) G) against this 26-kDa protein was much higher in UC patients (53.8%) than in the control sera (9.1%). The serum immunoreactivity (IgG) against a 50-kDa protein isolated from the whole cell protein of Escherichia coli (EC48-1) was also higher in UC patients (29.2%) than in normal controls (6.3%). Conclusions: These results suggest that B. vulgatus and a specific antibody response directed against it may play an important role in the pathogenesis of UC.

Relationship between Helicobacter pylori infection and smoking and drinking habits

Abstract: Background: Helicobacter pylori is a major cause of various gastroduodenal diseases. Some risk factors related to H. pylori infection have been reported; however, studies on the relationship between H. pylori infection and smoking or drinking habits have given conflicting results. In the present study, these relationships were investigated by collecting sera and information from 8837 subjects. Methods: Serum H. pylori immunoglobulin G antibody was measured by an enzyme-linked immunoassay. In addition to sex and age, information on smoking and drinking habits was collected by questionnaire. Age- and sex-adjusted odds ratios (95% confidence interval) of smoking and alcohol consumption were calculated for H. pylori seropositivity using logistic regression models. Results: Current smokers had a 0.82 (0.74–0.91)-fold greater risk of H. pylori seropositivity than those who had never smoked. Current cigarette consumption showed a dose-dependently negative association with H. pylori seropositivity, and the association between smoking and H. pylori infection was strong in younger subjects. Current drinkers had a 0.88 (0.79–0.98)-fold greater risk of H. pylori seropositivity than those who had never drunk alcohol. The volume of alcohol consumed showed a negative association with H. pylori seropositivity. Conclusions: In the current study, smoking was negatively associated with H. pylori infection. The risk of H. pylori seropositivity decreased linearly with cigarette consumption per day. Increased gastric acidity in the stomach through smoking may be a cause of the dose-dependently negative association between H. pylori and smoking. Drinking was negatively and dose-dependently associated with H. pylori positivity, although the effect of drinking was weaker than that of smoking. © 2000 Blackwell Science Asia Pty Ltd

Gastro oesophageal reflux disease in Asia

Abstract: Gastro-oesophageal reflux disease (GORD) occurs more frequently in Europe and North America than in Asia but its prevalence is now increasing in many Asian countries. Many reasons have been given for the lower prevalence of GORD in Asia. Low dietary fat and genetically determined factors, such as body mass index and maximal acid output, may be important. Other dietary factors appear to be less relevant. Increased intake of carbonated drinks or aggravating medicines may influence the increasing rates of GORD in some Asian countries but no strong evidence links other factors, such as the age of the population, smoking or alcohol consumption, to GORD. The management of GORD in Asia is similar to that in Europe and North America but the lower incidence of severe oesophagitis in Asia may alter the approach slightly. Also, because Asians tend to develop stomach cancer at an earlier age, endoscopy is used routinely at an earlier stage of investigation. Gastro-oesophageal reflux disease is essentially a motility disorder, so short-term management of the disease can usually be achieved using prokinetic agents (or histamine (H2)-receptor antagonists). More severe and recurrent GORD may require proton pump inhibitors (PPI) or a combination of prokinetic agents and PPI. The choice of long-term treatment may be influenced by the relative costs of prokinetic agents and PPI.

Diagnostic criteria for gastrointestinal carcinomas in Japan and Western countries: proposal for a new classification system of gastrointestinal epithelial neoplasia.

Abstract: Background: Large differences have been found between Western and Japanese pathologists in their diagnosis of adenoma/dysplasia and early carcinoma for gastric, colorectal and oesophageal epithelial neoplastic lesions. Common worldwide terminology based on clinical usefulness, that is, on neoplastic severity and depth of invasion, is needed. Methods: Thirty-one pathologists from 12 countries reviewed 35 gastric, 20 colorectal and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. Results: Suspected or definite carcinoma was diagnosed in 17-66% of gastric, in 5-40 t X> of colorectal, and in 10-67% of oesophageal slides by pathologists with a Western viewpoint, but in 77-94% of gastric, in 45-75% of colorectal and in 81-100% of oesophageal slides by pathologists with a Japanese viewpoint (from Japan, Germany, Austria and UK). Overall, there was poor agreement between the conventional Western and Japanese diagnoses (kappa values lower than 0.3 for gastric, colorectal and oesophageal lesions). There was much better agreement among the pathologists (kappa values higher than 0.5 for gastric and colorectal lesions) when the original assessments of the slides were regrouped into the five categories of the following classification of GI epithelial neoplasia we hereby propose: Cl, negative for neoplasia; C2, indefinite for neoplasia; C3, mucosal low-grade neoplasia (low-grade adenoma/dysplasia); C4, mucosal high-grade neoplasia (high-grade adenoma/dysplasia plus mucosal carcinoma); C5, submucosal invasion of neoplasia. Conclusions: The intercountry differences in the diagnoses of adenoma/dysplasia and early carcinoma can, in large part, be resolved by adopting terminology based on neoplastic severity and depth of invasion. Problems with defining intramucosal invasion are thus avoided. Moreover, grouping high-grade adenoma/dysplasia and mucosal carcinoma together in one category is clinically useful, as patients with small mucosal neoplastic lesions can be cured by endoscopic local resection.

Probiotics in infective diarrhoea and inflammatory bowel diseases

Abstract: Bacteria are present throughout the gastrointestinal tract, but their pattern and concentration vary greatly. Probiotics are living organisms that supply beneficial health effects to the host. So far the beneficial effects of probiotics have been shown, almost exclusively, under poorly defined experimental conditions. There are little convincing data from well-designed, double-blind controlled trials supporting health-promoting effects. The use of probiotics to treat gastrointestinal infections has produced contrasting results. Apart from information on rotavirus infection in children, there is no convincing evidence from controlled studies on the efficacy of probiotics in the prevention or treatment of infective diarrhoea. However, experimental and clinical studies suggest that there are potential therapeutic roles for probiotics in the treatment of inflammatory bowel diseases. This review focuses on the available data concerning the mechanisms of action of probiotics, and on the results from clinical studies using probiotics to treat infective diarrhoea and inflammatory bowel disease.

Prevalence of enteric pathogens among community based asymptomatic individuals.

Abstract: Background and Aims: The objective of this study was to describe the prevalence of pathogenic microorganisms in asymptomatic individuals in a community study in Melbourne, Australia. Methods: The study population was a subset of 2803 individuals participating in the Water Quality Study; a community based randomized trial. Faecal specimens (1091) were collected over a 3-month period from asymptomatic individuals. Specimens were tested for a range of bacteria including Salmonella, Shigella and Campylobacter species. Rotavirus and adenovirus were detected using a Rota-Adeno latex kit, and protozoa were detected using a permanent stain (modified iron-haemotoxylin). Results: Twenty-eight known pathogens were identified from the 1091 faecal specimens, a total carriage rate of 2.6%. Giardia species were present in 18 specimens (1.6%), Salmonella in four (0.4%), Campylobacter in one (0.1%), Cryptosporidium in four (0.4%) and adenovirus in one (0.1%). Blastocystis hominis was found in 65 specimens. The median age of those without a pathogen was 12.5 years compared with 6.6 years for those with a pathogen (P = 0.02). Conclusions: Except for Giardia, pathogens were rarely found in asymptomatic individuals in the community. The prevalence of pathogens was higher in children than adults. © 2000 Blackwell Science Asia Pty Ltd

Role of Kupffer cells and gut-derived endotoxins in alcoholic liver injury.

Abstract: The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol-induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.

Adult coeliac disease: prevalence and clinical significance.

Abstract: Background and Aims: Although coeliac disease is a common condition, the role of population screening is not clear. The aim of this study was to determine the prevalence and clinical significance of coeliac disease in the adult population of Christchurch, New Zealand. Methods: A total of 1064 adults randomly selected from the 1996 Christchurch electoral rolls were enlisted. The subjects were screened for coeliac disease using the anti-endomysial antibody test (EMA), and all those with positive tests were reviewed and underwent a small bowel biopsy. Results: Twelve of the 1064 persons tested (1.1%) were EMA positive and all had small bowel biopsy histology consistent with coeliac disease. Two of the 12 subjects were previously known to be EMA positive although neither had a small bowel biopsy. One additional subject with known and treated coeliac disease was also enrolled but was EMA negative. Thus, the overall prevalence of coeliac disease was 13 of 1064 subjects (1.2%, or 1 : 82), 10 of whom were newly diagnosed (0.9%, or 1 : 106) and three were previously known or suspected to have coeliac disease (0.3%, or 1 : 355). The prevalence in both sexes was similar. Nine of the 12 EMA-positive coeliac disease subjects identified by the use of screening reported symptoms, of which tiredness and lethargy were the most common. The subjects were of normal stature, although females tended to be lean. None of the subjects were anaemic, but four were iron deficient and four folate deficient. Five of the 12 had sustained bone fractures. Bone mineral density was reduced in males but not in females. Conclusions: The prevalence of coeliac disease in the adult population of Christchurch, New Zealand, is 1.2%. Unrecognized coeliac disease which was detected by population screening was three-fold more common than proven or suspected coeliac disease. Population screening may identify subjects who could benefit from treatment.

Sho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma.

Abstract: Herbal medicines, which have been used in China for thousands of years, are now being manufactured in Japan, in standardized form in terms of quality and quantities of ingredients. The Chinese herbal medicine Sho-saiko-to is a mixture of seven herbal preparations, which is widely administered in Japan to patients with chronic hepatitis and cirrhosis. In a prospective study, this herbal medicine was found to play a chemopreventive role in the development of hepatocellular carcinoma in cirrhotic patients. However, little is known about the mechanism by which Sho-saiko-to protects against hepatic fibrosis and carcinoma. Several laboratories, including ours, have clearly demonstrated the preventive and therapeutic effects of Sho-saiko-to on experimental hepatic fibrosis, as well as its inhibitory effect on the activation of hepatic stellate cells, which are the major types of collagen-producing cells. We provided evidence that Sho-saiko-to functions as a potent anti-fibrosuppressant via the inhibition of oxidative stress in hepatocytes and hepatic stellate cells and that its active components are baicalin and baicalein. In addition, Sho-saiko-to has anti-carcinogenic properties in that it inhibits chemical hepatocarcinogenesis in animals, acts as a biological response modifier and suppresses the proliferation of hepatoma cells by inducing apoptosis and arrests the cell cycle. Among the active components of Sho-saiko-to, baicalin, baicalein and saikosaponin-a have the ability to inhibit cell proliferation. It should be noted that baicalin and baicalein are flavonoids with chemical structures very similar to silybinin, which shows anti-fibrogenic activities. This may provide valuable information on the search for novel anti-fibrogenic agents.

Acute hepatic failure: a Western perspective.

Abstract: Acute hepatic failure (AHF) is an uncommon, devastating syndrome, which results in death or the need for liver transplantation in more than 50% of cases. While AHF has numerous causes, most cases are due to viral hepatitis and drug toxicity or idiosyncratic reactions. A significant group with indeterminate causation remains, despite careful investigation. In many of these cases a viral aetiology is suspected, although yet not proven. Major differences exist in the aetiology of AHF between the West and Eastern countries. A wider range of aetiologies exists in the West. Common causes include acetaminophen toxicity and idiosyncratic drug reactions, while viral hepatitis is less frequent. Hepatitis E infection is rarely seen in Western countries in contrast to its high prevalence in the East. The mainstay of AHF management is supportive care in an intensive care unit. Liver transplantation is now the standard of care in many Western liver units for individuals who have a less than 20% probability of survival. Lack of availability of donor livers at short notice remains a significant problem. Methods of liver support used while waiting for a donor liver or for the native liver to regenerate include bioartificial livers, extracorporeal liver-assist devices, extracorporeal whole organ perfusion (human and transgenic pig) and hepatocyte transplantation. The effectiveness of these methods remains unproven and awaits controlled clinical trials. Both transplantation and liver-support methods require specialized units and expensive and complicated equipment. Further research is necessary to identify modalities of therapy that would be effective as well as widely accessible.

Natural history of hepatitis C virus infection.

Abstract: Hepatitis C is a heterogeneous disease whose natural history is controversial and perplexing. However, it can be a pernicious disease and is responsible for considerable mortality and morbidity. More than 80% individuals infected with the hepatitis C virus (HCV) develop chronic infection; the remaining 10-20% develop spontaneous clearance with natural immunity. The majority of patients who develop chronic HCV infection are asymptomatic; but 60-80% develop chronic hepatitis as indicated by elevated ALT; around 30% maintain normal ALT. One-third of chronically infected patients develop progressive liver injury, fibrosis and cirrhosis over a period of 20-30 years, and 15% develop hepatocellular carcinoma. Acquiring infection after the age of 40 years, male sex, excessive alcohol-consumption, HBV or HIV co-infection and the immunosuppressive state have been identified as factors associated with progression of fibrosis and development of cirrhosis. The relationship between virus load, HCV genotype I and quasispecies variability and progression of live disease is controversial. In the present study on 141 patients with chronic HCV infection and established chronic liver disease, the median time to develop cirrhosis was 20 years. Progression to cirrhosis was faster (16 vs 20 years) in those who acquired infection after the age of 35 years, and in immunosuppressed patients (8 vs 21 years), whereas diabetes, sex and HBV co-infection were not associated with faster progression.

Acute hepatic failure in India: a perspective from the east.

Abstract: Acute hepatic failure (AHF) in India almost always presents with encephalopathy within 4 weeks of the onset of acute hepatitis. Further subclassification of AHF into hyperacute, acute and subacute forms may not be necessary in this geographical area, where the rapidity of onset of encephalopathy does not seem to influence survival. Viral hepatitis is the cause in approximately 95-100% of patients, who therefore constitute a more homogeneous population than AHF patients in the West. In India, hepatitis E (HEV) and hepatitis B (HBV) viruses are the most important causes of AHF; approximately 60% of cases are caused by to these viruses. Hepatitis B virus core mutants are very important agents in cases where hepatitis B results in AHF in this country. Half of the patients with AHF admitted to our centre are female, one-quarter of whom are pregnant. Therefore, pregnant females who contract viral hepatitis constitute a high-risk group for the development of AHF. However, the outcome of AHF in this group is similar to that in non-pregnant women and men. No association with any particular virus has been identified among sporadic cases of AHF. In our centre, approximately one-third of AHF patients survive with aggressive conservative therapy, whereas two-thirds of deaths occur within 72 h of hospitalization. Cerebral oedema and sepsis are the major fatal complications. Both fungal and gram-negative bacteria are major causes of sepsis. Among patients with AHF, despite the presence of sepsis, its overt clinical features (i.e. fever, leucocytosis) may be absent and objective documentation of the presence of sepsis in such patients is achieved by repeated culture of various body fluids. It should be possible to develop simple, clinical prognostic markers for AHF in this geographical region, in order to identify patients suitable for liver transplantation.

Role of heat shock proteins in gastric mucosal protection.

Abstract: Heat shock proteins (HSP) are crucial for the maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. Gastric surface mucous cells are the first line of defence against insults derived from ingested foods and Helicobacter pylori infection. Primary cultures of gastric surface mucous cells from guinea-pig fundic glands exhibited a typical heat shock response after exposure to elevated temperature or metabolic insults, such as ethanol and hydrogen peroxide, and they were able to acquire resistance to these stressors. Restraint and water immersion stress rapidly activated heat shock factor 1 (HSF1) in rat gastric mucosa within 15 min and induced HSP70 mRNA expression and its protein accumulation. The extent of the induction inversely correlated with the severity of mucosal lesions, suggesting an important role of HSP70 in gastric mucosal defence. This heat shock response appeared to be mediated by the alpha1A-adrenoceptor. The HSP70 family functions as a molecular chaperone and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to its chaperoning activities, HSP70 has been suggested to exert its cytoprotective action by protecting mitochondria and by interfering with the stress-induced apoptotic programme. Recently, we introduced geranylgeranylacetone as a non-toxic HSP70 inducer. This compound weakly stimulated HSP70 induction in cultured gastric mucosal cells and gastric mucosa by directly activating HSF1 and markedly augmented HSP70 induction in response to subsequent exposure to stress. Thus, non-toxic HSP70 inducers may have a potential benefit for the prevention and treatment of stress ulcer.

Decreased function of peripheral blood dendritic cells in patients with hepatocellular carcinoma with hepatitis B and C virus infection.

Abstract: Background: Tumour immunity does not seem to be induced effectively in tumour-bearing hosts, including in patients with hepatocellular carcinoma (HCC). One possible reason is that function of dendritic cells (DC) is decreased in such hosts. Methods: We evaluated T cell stimulatory activity and interleukin (IL)-12 production of DC and interferon (IFN)-γ and IL-10 production of T cells of peripheral blood from 12 control individuals and 21 patients with chronic hepatitis C virus (HCV) infection (six with chronic hepatitis (CH), eight with liver cirrhosis (LC) and 13 with HCC). Five hepatitis B virus (HBV)-infected patients with HCC were included as a disease control group. The DC were prepared by the culture of T cell-depleted populations of peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony stimulating factor and IL-4 for a total of 11–12 days. The cytokine levels were assayed by ELISA. To test the stimulatory function of DC in T cell proliferation, mytomycin C-treated DC were cultured with allogeneic T cells from a control. Results: When the T cell-stimulatory activity of DC was expressed as stimulation index value of [3H]-thymidine incorporation of T cells, the values were lower in HCV-infected HCC (2.6 ± 1.8, P < 0.01) than in controls (5.5 ± 2.0) and CH (5.0 ± 1.3). Staphylococcus aureus Cowan 1-induced IL-12 production of DC was decreased in HCV-infected HCC (P < 0.001, P < 0.01 and P < 0.05, respectively) compared with controls, CH and LC, while similar amounts of IL-10 were produced in patients and controls. Interleukin-10 and IFN-γ production of T cells in response to anti-CD3 antibody or IL-12 were equivalent between patient groups and controls, respectively. Similarly decreased DC function and normal T cell response were observed in HBV-infected HCC patients. Conclusions: These findings suggest that the depressed function of DC is associated with pathogenesis of HCC with HBV or HCV infection.