Showing papers in "Journal of Gastroenterology and Hepatology in 2002"

Non-alcoholic fatty liver disease.

Abstract: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.

Guidelines for the management of acute pancreatitis.

Abstract: Level 1: Evidence obtained from systematic reviews of all relevant randomized controlled trials. Level 2: Evidence derived from at least one properly designed randomized controlled trial. Level 3: Evidence from a well-designed control trial without randomization; or from well-designed cohort or case–control analytical studies; preferably from more than one center or research group; or from multiple time series with or without intervention. Level 4: Opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.This level signifies the need for further research. The final document was prepared and submitted to the Secretary General of OMGE for final scrutiny prior to publication for the World Congress of Gastroenterology. At the congress the recommendations were presented and questions and comments noted. These comments were incorporated into the final guidelines where appropriate.

Hepatitis B viral genotypes: clinical relevance and molecular characteristics

Abstract: Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.

Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent

Abstract: Background and Aim Certain hepatitis B virus (HBV) genotypes have been alleged to be associated with the development of cirrhosis and hepatocellular carcinoma (HCC), and the response to interferon therapy in Taiwanese patients. We undertook to study the prevalence and significance of HBV genotypes in the Indian subcontinent. Methods One hundred and thirty histopathologically proven chronic HBV-infected patients, including 52 incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive subjects (IDAHS) with chronic HBV infection (group I), 48 cirrhotics (group II) and 30 hepatocellular carcinoma (HCC; group III) patients were studied. Hepatitis B virus genotypes were determined by using restriction fragment length polymorphism, and direct sequencing of the s gene including the ‘a’ determinant region. Results Only genotypes A (46%) and D (48%) were found in the chronic HBV-infected patients. A mixed infection with genotypes A and D was seen in 6% of patients. Genotype A was found in 42, 48 and 50%, and genotype D in 48, 50 and 47% of group I, II and III patients, respectively (P = NS). The patients who had mixed genotypes were significantly younger (P 4 as compared to genotype A (53 vs 32%, P < 0.05). Similarly, genotype D was associated with more severe liver diseases (61 vs 30%, P < 0.05). Genotype D was more prevalent in HCC patients of < 40 years of age, as compared to IDAHS (63 vs 44%, P = 0.06). Conclusions (i) Hepatitis B virus genotypes A and D are prevalent in chronic liver disease patients of Indian origin; and (ii) HBV genotype D is associated with more severe diseases and may predict the occurrence of HCC in young patients.

Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics.

Abstract: Background and Aims: Fatty liver is not uncommon in many countries, including Japan, and is mainly caused by alcohol usage and obesity. The aim of this study was to determine the incidence and causative factors of fatty liver in Japanese adults. Methods: The clinical characteristics of 3432 Japanese adults who visited our hospital between January and December 2000 for thorough medical examinations were recorded including sex, age, body mass index (BMI), percentage body fat measurement using a bipedal bioimpedance instrument, history of alcohol intake, blood pressure, serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase, total cholesterol, triglyceride, uric acid, fasting blood glucose (FBG), and liver status by ultrasonography (USG). Results: Of 3432 participants, 747 (21.8%) were diagnosed as having fatty liver by USG, 1873 (54.6%) were ‘daily alcohol drinkers’, and 698 (20.3%) were overweight (BMI ≥ 25 kg/m2). Fatty liver was more frequent in men and overweight subjects (P < 0.01), whereas there was no significant difference in the proportion of the ‘daily alcohol drinker’ between fatty liver and non-fatty liver participants. The logistic regression analysis showed that BMI, ALT, and triglyceride were independent predictors of fatty liver in both sexes, and FBG, uric acid, percentage body fat, and total cholesterol were independent predictors of fatty liver only in men. It was noted that 319 (9.3%) were non-alcoholic individuals with fatty liver, and 141 (4.1%) were non-alcoholic and non-overweight individuals with fatty liver. The logistic regression analysis showed that percentage body fat was an independent predictor of fatty liver in non-alcoholic and non-overweight participants in both sexes, although non-significant in women in the whole group. Conclusions: In our study population, 21.8% had fatty liver diagnosed by USG, 9.3% were non-alcoholic with fatty liver, and 4.1% were non-alcoholic and non-overweight with fatty liver. Our results suggest that central body fat distribution can correlate with the development of fatty liver, and that measurement of percentage body fat is useful to assess the etiology of fatty liver in non-alcoholic and non-overweight participants, particularly women.

Non‐alcoholic fatty liver disease: An overview

Abstract: Non-alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non-alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of 'burned-out' NASH. Although NAFL and NASH are associated with insulin-resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure.

Clinical implications of hepatogenous diabetes in liver cirrhosis.

Abstract: Background: Hepatogenous diabetes is a common complication of liver cirrhosis. The aim of the present study was to examine the clinical and therapeutic implications and the prognostic significance of hepatogenous diabetes in patients with liver cirrhosis. Methods: The prospective cohort study was conducted in 52 patients with histologically confirmed liver cirrhosis (44% Child A, 37% Child B, 19% Child C). The examination included a history, determination of basal C-peptide and glycosylated hemoglobin (HbA1c) and, in some cases, a 3 h oral glucose tolerance test with 100 g glucose. Patients were also examined for signs of diabetic retinopathy and information on the further course of illness was obtained. Results: Seventy-one percent of patients with liver cirrhosis had manifest diabetes, 25% had impaired glucose tolerance and only 4% had normal glucose tolerance. In most cases, the hepatogenous diabetes was clinically asymptomatic. Sixteen percent of patients with hepatogenous diabetes had a family history of diabetes; only 8% had retinopathic complications. Within 5.6 ± 4.5 years after diagnosis of liver cirrhosis, 52% of the diabetics had died, mainly of complications of the cirrhosis. There were no diabetes-associated or cardiovascular deaths. Conclusions: Hepatogenous diabetes differs from type 2 diabetes in that there is less often a positive family history and that the cardiovascular and retinopathic risk is low. The prognosis of cirrhotic patients with diabetes is more likely to be negatively affected by the underlying hepatic disease and its complications than by the diabetes. Antihyperglycemic treatment of hepatogenous diabetes should always be carefully weighed up in each individual case.

Non‐cirrhotic portal fibrosis (idiopathic portal hypertension): Experience with 151 patients and a review of the literature

Abstract: Background: Non-cirrhotic portal fibrosis (NCPF), the equivalent of idiopathic portal hypertension in Japan and hepatoportal sclerosis in the United States of America, is a common cause of portal hypertension in India. The clinical features, portographic and histological findings, and management of 151 patients with non-cirrhotic portal fibrosis are presented. Methods: The disease is diagnosed by the presence of unequivocal evidence of portal hypertension in the definite absence of liver cirrhosis and extrahepatic portal vein obstruction (EHPVO). Retrospective analysis of records of 151 patients with NCPF was analyzed for the clinical presentation, physical findings, laboratory tests, radiological and histological findings, and for the outcome of treatment. Results: The disease is characterized by massive splenomegaly with anemia, preserved liver function and benign prognosis in a majority of patients. Splenoportovenography (SPV) showed massive dilatation of the portal and splenic veins, and the presence of collaterals. Twenty-four (15.9%) patients showed evidence of natural/spontaneous shunts (splenorenal 15, umbilical nine) on SPV; these patients had a lower incidence of variceal bleeding. Liver histology demonstrated maintained lobular architecture, portal fibrosis of variable degree, sclerosis and obliteration of small-sized portal vein radicles, and subcapsular scarring with the collapse of the underlying parenchyma. Piecemeal or hepatocytic necrosis was absent in all histology specimens. Three patients showed nodular transformation along with abnormal liver functions, and may represent late manifestation of NCPF where features are similar to those seen in patients with incomplete septal cirrhosis. In the initial part of the study, surgery (side-to-side lieno-renal shunt) was the preferred modality of treatment, however, endoscopic sclerotherapy or variceal ligation has now become the preferred first line of management of variceal bleeding. Conclusions: The epidemiological and clinical features of NCPF have more similarity to IPH than has previously been documented. The development of spontaneous shunts tends to protect these patients from variceal bleeding.

Cholangiocarcinoma: recent progress. Part 1: epidemiology and etiology.

Abstract: An attempt is made in this review to update the reader on recent developments and progress in the study of cholangiocarcinoma: a major primary carcinoma of the liver with a very poor prognosis. Knowledge of the cell biology and physiological functions of the cholangiocyte has recently so progressed that our understanding of cholangiocarcinogenetic mechanism is expected to follow. The first part of the review deals with semantic problems, temporal changes in the incidence of cholangiocarcinoma and geographic differences in epidemiology, etiologic factors (particularly opistorchiasis in Thailand and hepatolithiasis in the Far East), and discusses a recently disclosed role of hepatitis C virus infection (30% of cholangiocarcinoma patients have antibodies against hepatitis C virus in Japan).

Hepatitis C risk factors in Iranian volunteer blood donors: A case–control study

Abstract: Background: In order to evaluate some possible risk factors for the spread of hepatitis C infection a case–control study was undertaken. Methods: The study population consisted of first time blood donors referred to the Iranian Blood Transfusion Organization. Enzyme-linked immunosorbent assay and recombinant immunoblot assay anti-hepatitis C virus (HCV) tests were performed for all samples. Risk factors were evaluated using a questionnaire. A stepwise forward logistic regression analysis was used. Results: The case group consisted of 193 HCV-positive donors, and 196 HCV-negative donors comprised the control group. Transfusion, undergoing endoscopy, extramarital sexual activities, non-intravenous (i.v.) drug abuse, i.v. drug abuse, and receiving wounds at war were found to be independent risk factors of being HCV-positive (Odds ratio: 17, 4, 42.2, 34.4, 52.8 and 5.2, respectively). No apparent risk factors could be demonstrated in 24.5% of the positive cases. Conclusion: This study could be of particular interest because of the low seroprevalence of hepatitis C and the religious culture of the study population. There are certain medical procedures, lifestyle patterns, and customs and cultural matters in Iran that predispose people to a number of HCV risk factors.

Non-alcoholic steatohepatitis: Definitions and pathogenesis

Abstract: This description remains appropriate because nonalcoholic fatty liver disease (NAFLD) can range from simple steatosis, through NASH and fibrosis to cirrhosis with fat. 2 In addition to fat, the histological diagnosis of NASH ideally requires evidence of (i) hepatocyte injury, manifest by swollen or ‘ballooned’ cells; (ii) an inflammatory infiltrate, predominantly neutrophils, with or without (iii) fibrosis, typically perivenular/pericellular in distribution. Each of these features can be graded to derive a score recently proposed by Brunt et al. 3 Rigorous exclusion of alcohol as a cause of the histology is, of course required and this is best achieved by a combination of repeated questioning of patients and ideally friends/relatives, frequent random blood alcohol estimations and measurement of mean cell corpuscular volume (MCV). No pattern of liver blood test abnormalities is either specific or sensitive enough to distinguish between NAFLD and alcohol-related liver disease.

Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species‐specific antibody

Abstract: Background: Microbial agents are a possible cause of ulcerative colitis. We have previously reported evidence of bacteria invading the colonic mucosa of patients with ulcerative colitis. We have isolated bacteria from inflamed colonic mucosa, examined the localization of the species in the mucosa, and assayed for serum antibodies to the bacteria. Methods: Cohorts of 31 per group were enrolled from patients with active ulcerative colitis, Crohn's disease, ischemic colitis, and colon adenomas. A group of 31 healthy controls were also studied. The presence of bacteria in biopsies of patients with ulcerative colitis was analyzed by both isolation and immunohistochemistry. Sera from patients were tested for bacterial antibodies using both Western blots and enzyme-linked immunosorbent assay (ELISA). Results: Only sera from patients with ulcerative colitis gave specific reactions with Fusobacterium varium in Western blot assays. The detection rate of specific bands was higher for patients with ulcerative colitis (61%) than for subjects with either Crohn's disease (13%) or healthy controls (29%) (P < 0.001 and P = 0.021, respectively). The ELISA showed that the mean optical densities with extracts of F. varium as antigen were significantly higher for ulcerative colitis patients than for subjects with either Crohn's disease or healthy controls (P < 0.001). Immunohistochemical detection of F. varium in colonic mucosa was significantly higher in patients with ulcerative colitis (84%) than for subjects with either Crohn's disease (16%) or other controls (3–13%) (P < 0.001). Conclusions:Fusobacterium varium bacteria were present in a significant number of patients with active ulcerative colitis, and should be tested in therapeutic trials in order to confirm the causal relationship between F. varium and ulcerative colitis.

Hepatitis B e-antigen negative chronic hepatitis B.

Abstract: These special populations of chronic hepatitis B (CHB) patients with viral replication were branded as ‘antiHBe-positive’ or ‘HBeAg-negative’ chronic hepatitis B (e-CHB). The molecular basis of HBeAg-negative HBV infection was identified: a guanine (G) to adenine (A) change at nucleotide 1896 (G1896A), creates a novel translational stop codon (at precore codon 28) leading to premature termination of the translation of the precore protein and absence of HBeAg secretion. 5 Subsequently, other mutations in the precore or basal core promoter (BCP) region which downregulate or abolish HBeAg production have also been described. 6

Genotype‐specific mechanisms for hepatic steatosis in chronic hepatitis C infection

Abstract: Background: Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. Methods: In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein–cholesterol, high-density lipoprotein–cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). Results: By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Conclusions: Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C.

Herbal medicines for liver diseases in India.

Abstract: The use of natural remedies for the treatment of liver diseases has a long history, starting with the Ayurvedhic treatment, and extending to the Chinese, European and other systems of traditional medicines. The 21st century has seen a paradigm shift towards therapeutic evaluation of herbal products in liver diseases by carefully synergizing the strengths of the traditional systems of medicine with that of the modern concept of evidence-based medicinal evaluation, standardization of herbal products and randomized placebo controlled clinical trials to support clinical efficacy. The present review provides the status report on the scientific approaches made to herbal preparations used in Indian systems of medicine for the treatment of liver diseases. In spite of the availability of more than 300 preparations for the treatment of jaundice and chronic liver diseases in Indian systems of medicine using more than 87 Indian medicinal plants, only four terrestrial plants have been scientifically elucidated while adhering to the internationally acceptable scientific protocols. In-depth studies have proved Sylibum marianum to be anti-oxidative, antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating and liver regenerative. Glycyrrhiza glabra has been shown to be hepatoprotective and capable of inducing an indigenous interferon. Picrorhiza kurroa is proved to be anti-inflammatory, hepatoprotective and immunomodulatory. Extensive studies on Phyllanthus amarus have confirmed this plant preparation as being anti-viral against hepatitis B and C viruses, hepatoprotective and immunomodulating, as well as possessing anti-inflammatory properties. For the first time in the Indian systems of medicine, a chemo-biological fingerprinting methodology for standardization of P. amarus preparation has been patented.

Pyogenic liver abscess: Retrospective analysis of 80 cases over a 10‐year period

Abstract: Background: A total of 80 patients with pyogenic liver abscess managed at a single institution over a 10-year period were studied. Methods: The clinical features, laboratory, imaging, and microbiologic findings, management strategy, and final outcome were studied. Results: Fever and chills, leucocytosis and elevated alkaline phosphatase were the most common clinical and laboratory findings. Forty-one percent of patients were diabetic and 61% had biliary pathology. Systemic antibiotics and image-guided aspiration had a success rate of 94%. By multiple logistic regression analysis, malignancy on presentation (P = 0.011) was an independent risk factor associated with mortality. A past history of endoscopic sphincterotomy was an independent factor associated with resolution of liver abscess within 6 weeks (P = 0.03). Conclusion: Pyrexia, leucocytosis, elevated alkaline phosphatase, presence of diabetes, and underlying biliary pathology are common clinical and laboratory findings in patients with pyogenic liver abscess. Malignancy was associated with a poor outcome. Previous endoscopic sphincterotomy was a good prognostic factor for early resolution. © 2002 Blackwell Publishing Asia Pty Ltd

Characteristic endoscopic and magnified endoscopic findings in the normal stomach without Helicobacter pylori infection.

Abstract: Background and Aims: The aim of this study was to clarify the endoscopic features of the Helicobacter pylori (H. pylori)-free stomach by examining the arrangement of minute points visible on the corpus. Since these points were clarified by magnifying endoscopy as collecting venules, this finding was termed ‘regular arrangement of collecting venules (RAC)’. The findings from more endoscopic studies are presented and the differences between magnified views of the normal and H. pylori-infected corpus and antrum are described in particular. Methods: The study group consisted of 557 patients who were subjected to endoscopy and checked for H. pylori. The RAC in each patient was assessed. Magnifying endoscopy in 301 patients was used to examine the corpus and in 94 patients to examine the antrum. Results: One hundred and fifty-eight patients had normal stomachs without H. pylori. We diagnosed 389 patients with H. pylori gastritis. In 10 patients H. pylori was not detected, but inflammation was present. Of the 158 patients with H. pylori-negative normal stomachs, 151 had RAC. As a determinant of the normal stomach without H. pylori infection, the presence of RAC had 93.8% sensitivity and 96.2% specificity. All 30 patients with H. pylori-negative normal stomachs had a well-defined ridge pattern (wDRP) on the antrum as observed under magnifying endoscopy. As a determinant of the normal stomach without H. pylori infection, wDRP had a specificity of 100%, but a sensitivity of only 54.5%. Conclusions: The presence of RAC is characteristic of a normal stomach without H. pylori. Magnified views of the normal antrum were different from that of the normal corpus.

New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions

Abstract: Gastrointestinal malignancies continue to be the second leading cause of cancer-related deaths in the developed world. The early detection and treatment of gastrointestinal preneoplasms has been demonstrated to significantly improve patient survival. Conventional screening tools include standard white light endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy have been undertaken for groups at high risk. Unfortunately, the poor sensitivity associated with WLE is a significant limitation. In this regard, major efforts continue in the development and evaluation of alternative diagnostic techniques. This review will focus on notable developments made at the forefront of research in modern gastrointestinal endoscopy based on novel optical endoscopic modalities, which rely on the interactions of light with tissues. Here we present the 'state-of-the-art' in fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and immunofluorescence endoscopy. These new developments may offer significant improvements in the diagnosis of early lesions by allowing for targeted mucosal excisional biopsies, and perhaps may even provide 'optical biopsies' of equivalent histological accuracy. This enhancement of the endoscopist's ability to detect subtle preneoplastic changes in the gastrointestional mucosa in real time and improved staging of lesions could lead to curative endoscopic ablation of these lesions and, in the long term, improve patient survival and quality of life.

Non‐cirrhotic portal fibrosis: Current concepts and management

Abstract: Non-cirrhotic portal hypertension (NCPH) comprises diseases having an increase in portal pressure (PP) due to intraheptic or prehepatic lesions, in the absence of cirrhosis. The lesions are generally vascular, either in the portal vein, its branches or in the perisinusoidal area. Because the wedged hepatic venous pressure is near normal, measurement of intravariceal or intrasplenic pressure is needed to assess PP. The majority of diseases included in the category of NCPH are well-characterized disease entities where portal hypertension (PHT) is a late manifestation and, hence, these are not discussed. Two diseases that present only with features of PHT and are common in developing countries are non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO). Non-cirrhotic portal fibrosis is a syndrome of obscure etiology, characterized by 'obliterative portovenopathy' leading to PHT, massive splenomegaly and well-tolerated episodes of variceal bleeding in young adults from low socioeconomic backgrounds, having near normal hepatic functions. In some parts of the world, NCPF is called idiopathic portal hypertension (IPH) or 'hepatoportal sclerosis'. Because 85-95% of patients with NCPF and EHPVO present with variceal bleeding, treatment involves management with endoscopic sclerotherapy (EST) or variceal ligation (EVL). These therapies are effective in approximately 90-95% of patients. Gastric varices are another common cause of upper gastrointestinal bleeding in these patients and these can be managed with cyanoacrylate glue injection or surgery. Other indications for surgery include failure of EST/EVL, and symptomatic hypersplenism. The prognosis of patients with NCPF is good and 5 years survival in patients in whom variceal bleeding can be controlled has been reported to be approximately 95-100%.

Tumor necrosis factor-α and transforming growth factor-β reflect severity of liver damage in primary biliary cirrhosis

Abstract: BACKGROUND AND AIMS The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-alpha and TGF-beta and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-alpha and TGF-beta levels in patients with PBC. METHODS We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-alpha and TGF-beta levels were quantified by enzyme-linked immunoabsorbent assay. RESULTS Baseline levels of TNF-alpha were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-alpha levels and progression risk score compared to placebo-treated patients. TNF-alpha and TGF-beta levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients. CONCLUSIONS Serum TNF-alpha and TGF-beta levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.

Prevalence of irritable bowel syndrome in Hong Kong

Abstract: Background and Aims: As part of a public education program, the Hong Kong Society of Gastrointestinal Motility studied the prevalence of irritable bowel syndrome (IBS) in the community, which was based on the recently published Rome II criteria. The distribution of diarrhea or constipation-predominant IBS subtypes, the prevalence of bowel symptoms and the predictors of health-care seeking were also studied. Methods: Among 1797 randomly selected respondents, 1000 successful telephone interviews (56%) were conducted from August 2000 to December 2000, using a validated questionnaire in Chinese that looked into demographic data and various bowel symptoms during the past year. Results: The 12-month prevalence of IBS as defined by the Rome II criteria in Hong Kong was 6.6%. The female to male ratio was 1.3:1, but this ratio was the same in the control group. The distribution of IBS patients into diarrhea predominant, constipation predominant, and non-specific subtypes was 27, 17 and 56%, respectively. The predominant symptom in the IBS group was pain (54.5%), followed by urgency (15%), abdominal distension (15%) and diarrhea (11%). Forty-seven percent of IBS patients sought medical attention and only 21% of them knew that they had IBS. Moderate to severe pain severity (odds ratio 3.7, 95% CI 1.02–13) and mucus in stool (odds ratio 3.57, 95% CI 1.18–10.7) were associated with health-care seeking in univariate analysis. The prevalence of bowel symptoms such as urgency, straining, feeling of incomplete defecation, mucus in stool and abdominal distension ranged from 11 to 41%. Conclusion: The prevalence of IBS in Hong Kong was 6.6%, and the female to male ratio was similar to the control group. The majority was of non-specific IBS subtype. Gross underdiagnosis (21%) by Western practitioners was noted. © 2002 Blackwell Publishing Asia Pty Ltd

Disorders of gastrointestinal motility: towards a new classification.

Abstract: can be learnt from the patient. In the last decade, the ‘Delphic’ technique has been used to try and define combinations of symptoms in the belief, or hope, that specific symptom patterns correspond to specific underlying disorders. The ‘Rome criteria’ for the definition and diagnosis of functional gastrointestinal disorders have received much attention. Unfortunately, consensus of opinions by experts does not, per se, confer scientific validity. Evidence-based medicine requires not consensus, but evidence. We have reappraised the problem of classifying motor disorders by relying on what can be established by the detection of abnormal motor patterns, usually, but not invariably, associated with the altered movement of the contents of the digestive tube. In some, but not yet all, disorders, this approach is reinforced by identification of underlying pathological change in enteric innervation or musculature. While we remain aware that the association between symptoms—the perception that drives patients to seek help—and motor abnormalities is not always clear, we have taken the view that objectively reproducible alterations in organ function provide a robust basis for taxonomy. Such problems are not unique to gastroenterology; as an example, the association between dyspnea and specific pulmonary pathologies is not always clear, but dyspnea is a useful indication of abnormal respiratory function indicative of disease. Clinicians may feel dismayed that we have not elected to define two commonly used terms: ‘functional dysINTRODUCTION

Chronic pancreatitis: Asia-Pacific consensus report.

Abstract: Current knowledge about chronic pancreatitis (CP) is limited and there is a particular dearth of information about the entity known as tropical pancreatitis. A consensus working party was convened by the Trustees of the Journal of Gastroenterology and Hepatology Foundation to conduct a systematic investigation into available evidence about the epidemiology, etiopathogenesis, diagnosis and management of CP. A literature search and formal survey of international experts in the field were used to assemble reliable evidence about these issues. The present review summarizes the results of the working party's findings and presents a series of practice guidelines to improve diagnosis, investigation and treatment of patients with CP, particularly those in the Asia-Pacific region. Areas for further research have also been identified.

Escherichia coli as a cause of diarrhea.

Abstract: Escherichia coli is the best-known member of the normal microbiota of the human intestine and a versatile gastrointestinal pathogen. The varieties of E. coli that cause diarrhea are classified into named pathotypes, including enterotoxigenic, enteroinvasive, enteropathogenic and enterohemorrhagic E. coli. Individual strains of each pathotype possess a distinct set of virulence-associated characteristics that determine the clinical, pathological and epidemiological features of the diseases they cause. In the present brief review, we summarize the key distinguishing features of the major pathotypes of diarrheagenic E. coli. Knowledge of the pathogenic mechanisms of these bacteria has led to the development of rational interventions for the treatment and prevention of E. coli-induced diarrhea. In addition, investigations into E. coli virulence are providing useful insights into the origins and evolution of bacterial pathogens more generally.

Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with Terlipressin: A retrospective analysis

Abstract: Background and Aim: Terlipressin has been proposed to treat renal failure in patients with type 1 hepatorenal syndrome (HRS). However, the predictive factors for improved renal function and survival are unknown in patients with type 1 HRS treated with terlipressin. The aim of the present retrospective study was to investigate the predictive factors and prognosis of patients with type 1 HRS treated with terlipressin. Methods: The clinical charts of 18 consecutive patients with cirrhosis and type 1 HRS treated with terlipressin were studied. The predictive factors for improved renal function and survival were identified using univariate analyses. Results: Improved renal function, indicated by a significant decrease in serum creatinine (61 ± 4%), occurred in 11 (60%) patients. The only predictive factor for improved renal function was a Child–Pugh's score ≤13 at the time of diagnosis of HRS (P = 0.02). Fifteen patients (83%) died at 45 days and the median survival was 24 days. Of the three patients who survived, two underwent successful orthotopic liver transplantation. Three predictive factors for survival were identified: absence of a precipitating factor for HRS (P = 0.012); improved renal function during terlipressin therapy (P = 0.05); and a dose of terlipressin ≥3 mg/day (P = 0.04). Conclusions: In patients with type 1 HRS treated with terlipressin, patients with improved renal function had less severe cirrhosis (Child–Pugh >10 but ≤13) than patients without. The predictive factors for survival were the absence of a precipitating factor for HRS, the terlipressin-induced improvement in renal function and a dose of terlipressin of at least 3 mg/day. These findings suggest that a randomized controlled trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed. © 2002 Blackwell Publishing Asia Pty Ltd

A new prebiotic from germinated barley for nutraceutical treatment of ulcerative colitis.

Abstract: A germinated barley foodstuff (GBF) containing glutamine-rich protein and hemicellulose-rich fiber was made from brewer's spent grain, by physical isolation. Our previous studies demonstrated that GBF supported maintenance of epithelial cell populations, facilitated epithelial repair, and suppressed epithelial nuclear factor kappaB-DNA-binding activity through generating increased short-chain fatty acid (especially butyrate) production by luminal microflora, which includes Bifidobacterium and Eubacterium, thereby preventing experimental colonic injury. The fiber fraction also modulates stool water content because of its high water-holding capacity. The patients with mild to moderate active ulcerative colitis who had been unresponsive to or intolerant of standard treatment received 20-30 g GBF, feeding daily in a non-randomized, open-label fashion. At 4 weeks, this treatment resulted in a significant clinical and endoscopic improvement. The improvement was associated with an increase in stool butyrate concentrations. These results indicate that GBF feeding is a potentially new, attractive prebiotic treatment in patients with ulcerative colitis. The potency of GBF on modulating microflora, as well as the high water-holding capacity, may play an important role in treatment and prolongation of remission in ulcerative colitis.

Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance.

Abstract: Background and Aims : The natural immunomodulator, lactoferrin, is widespread among various biological fluids and is known to exert an anti-inflammatory effect. However, there has been only one study that examined the mode of action of lactoferrin in reducing intestinal damage. We investigated the therapeutic role of lactoferrin and its effect on the levels of pro-inflammatory and anti-inflammatory cytokines, by using a rat model of dextran sulfate sodium (DSS) induced-colitis. Methods: Male Sprague–Dawley rats were given distilled drinking water containing 2.5% (wt/vol) synthetic DSS ad libitum. Bovine lactoferrin was given once daily through gavage, starting 3 days before beginning the DSS administration, until death. The whole colon was removed to be examined macroscopically and histologically. Myeloperoxidase activity, and pro-inflammatory and anti-inflammatory cytokines in the colonic tissue were also measured. Results: Dextran sulfate sodium-induced colitis was attenuated by oral administration of lactoferrin in a dose-dependent manner, as reflected by improvement in clinical disease activity index, white blood cell count and hemoglobin concentration, macroscopic and histological scores, and myeloperoxidase activity. Reduced inflammation in response to lactoferrin was correlated with the significant induction of the anti-inflammatory cytokines, interleukin-4 and interleukin-10, and with significant reductions in the pro-inflammatory cytokines, tumor necrosis factor α, interleukin-1β, and interleukin-6. Conclusions: We concluded that oral administration of lactoferrin exerts a protective effect against the development of colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease. © 2002 Blackwell Publishing Asia Pty Ltd

Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model.

Abstract: Background: As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long-standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia-carcinoma sequence in a novel repeated colitis model in mice is documented. Methods: Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans. Results: Multiple colorectal tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time-course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis-affected mucosal epithelia. Conclusion: Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia–invasive carcinoma sequence in ulcerative colitis.

Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requiring surgery

Abstract: Background and Aims : Up to one-third of patients with ulcerative colitis (UC) need to undergo surgery, but the factors that exacerbate inflammation remain unclear. The authors hypothesize that excessive apoptosis reported in active UC may disrupt epithelial defenses and exacerbate the disease. The aim of the present study was to clarify whether apoptotic epithelial cells and histiocytes engulfing them increased in patients with active UC who ultimately require surgery (UC-S) rather than those receiving medication alone (UC-M). Methods: The study included 29 patients with UC-S, 35 with UC-M, 18 with infectious colitis, and 16 healthy controls. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Using biopsy specimens taken from the most severely inflamed rectosigmoid mucosa as determined endoscopically, the apoptotic index (apoptotic cells/epithelial cells,%) and density (per mm2) of lamina propria histiocytes positive for CD68 were then evaluated. Statistical differences were tested with the Mann–Whitney U-test. Results : The apoptotic indices in UC-M patients were significantly higher than those in controls (P < 0.05) but almost equal to those in infectious colitis patients. In the upper and lower halves of the mucosa, both apoptotic indices and histiocyte densities were significantly higher for UC-S than in UC-M (P < 0.01). Ratios of the mean apoptotic index for UC-S to that for UC-M exceeded 3.4, while ratios of the mean histiocyte density were limited to approximately 1.6. Conclusions : The results suggest that epithelial apoptosis is a non-specific phenomenon and that an increased number of apoptotic cells exceeding histiocyte phagocytic capacity may play a part in the disruption of epithelial defenses and further accelerate mucosal inflammation. © 2002 Blackwell Publishing Asia Pty Ltd

Serum ferritin and Helicobacter pylori infection in children: A sero-epidemiologic study in Korea

Abstract: Background : Helicobacter pylori infection is known to affect iron metabolism and serum ferritin levels, which are reduced in adults with H. pylori infection. The aim of the present study was to investigate the association between H. pylori infection and iron status in healthy Korean children. Methods : The H. pylori seropositivity in 753 schoolchildren aged 6–12 years was screened for using an ELISA and confirmed by western blot analyses. Serum ferritin levels were measured using an immunoradiometric assay in 36 H. pylori-seropositive children and in 72 age- and gender-matched seronegative controls. Results : The median serum ferritin levels were significantly lower in H. pylori-seropositive children than in seronegative controls (24 vs 39 ng/mL; P < 0.001). The prevalence of iron deficiency (ferritin < 15 ng/mL) in H. pylori-seropositive children was significantly higher (13.9%) than in seronegative children (2.8%). This association persisted after adjusting for age and their socioeconomic status (odds ratio, 5.6; 95% confidence interval, 1.0–30.6). Conclusion : Serum ferritin levels are reduced in children with H. pylori infection. The H. pylori infection may lead to iron deficiency in children. © 2002 Blackwell Publishing Asia Pty Ltd