Showing papers in "Journal of Gastroenterology and Hepatology in 2004"

The liver as an immunological organ

Abstract: The liver is an immunologically distinct organ that contains its own unique population of cells of the innate and adaptive cellular immune response. The liver is known as a site of inflammatory immune responses as well as a site of tolerance induction. This dual function is important to understand the pathogenesis of infectious liver diseases and to understand induction of tolerance upon exposure to oral and allograft antigens. This review will address the unique role of the liver in the immune system.

Non-alcoholic steatohepatitis in type 2 diabetes mellitus.

Abstract: Background and Aims: Non-alcoholic steatohepatitis (NASH) is commonly associated with type 2 diabetes mellitus (DM). Prevalence of NASH in type 2 DM has not been well studied and there is an epidemic rise in type 2 DM in Asian and Western populations. Its association with chronic liver disease in the form of NASH makes it an important health problem. Hence we have studied its prevalence and correlation of biochemical parameters with histological grades of non-alcoholic fatty liver disease (NAFLD) in otherwise asymptomatic type 2 DM patients. Methods: One hundred and forty-eight individuals were screened. Forty-eight individuals were excluded due to history of alcohol intake or liver disease as a result of other causes. One hundred non-alcoholic individuals with type 2 DM underwent abdominal ultrasonography (US abdomen). Forty-nine patients had evidence of fatty liver on US abdomen, and 32 of these 49 patients underwent liver biopsy. Results: Four of 32 (12.5%) individuals had steatosis alone. Mild, moderate and severe NASH was present in 21/32 (65.5%), 4/32 (12.5%) and 3/32 (9.35%), respectively. Fibrosis was present in 7/32 (21.8%) patients (four grade 1 and three grade 3). There was no significant difference in body mass index (BMI), transaminase levels, serum cholesterol and triglyceride levels among patients with non-alcoholic fatty liver disease. Conclusion: We conclude that the prevalence of NASH is high in type 2 DM patients and liver biopsy is the only investigation to differentiate between non-alcoholic fatty liver and steatohepatitis.

Clinical usefulness of carbohydrate antigen 19‐9 as a screening test for pancreatic cancer in an asymptomatic population

Abstract: Background and Aim: Although the prognosis for pancreatic cancer is generally poor, it is well known that the survival rate for resected pancreatic cancer is much higher than that for more conservative treatment. The importance of early detection is emphasized for resection of pancreatic cancer. Measurement of serum carbohydrate antigen (CA) 19-9 has shown satisfactory sensitivity and predictive value in symptomatic patients, but no available data has been found on healthy asymptomatic subjects. Thus, the authors aimed to determine the clinical usefulness of CA 19-9 as a screening tool for pancreatic cancer in asymptomatic subjects. Methods: From December 1994 to November 2000, 70 940 asymptomatic persons visiting the Health Promotion Center at the Samsung Medical Center, Seoul, Korea, participated. All subjects underwent abdominal ultrasonography and serum CA 19-9 measurement. The authors analyzed the sensitivity, specificity, and predictive values of CA 19-9 for detecting pancreatic cancer. Also, those subjects who had a serum CA 19-9 level above the cut-off value were followed up using a serial check of CA 19-9, computed tomography, or endoscopic retrograde cholangiopancreatography. Results: The number of subjects with a level of CA 19-9 above the cutoff of 37 U/mL was 1063 (1.5%), including four cases diagnosed with pancreatic cancer. The prevalence of pancreatic cancer over the age of 30 years is 13.66 per 100 000 population in Korea. Therefore, the sensitivity is 100% and the specificity 98.5%. However, the positive predictive value of CA 19-9 for detecting pancreatic cancer is only 0.9% in the asymptomatic population. Conclusion: Mass screening for pancreatic cancer using CA 19-9 levels in asymptomatic subjects is ineffective because of a very low positive predictive value, despite its high sensitivity and specificity.

Four years of lamivudine treatment in Chinese patients with chronic hepatitis B.

Abstract: Background and Aims: This study assessed the efficacy and safety of up to 4 years of lamivudine treatment and the clinical relevance of the emergence of YMDD-variant hepatitis B virus (HBV). Methods: Fifty-eight Chinese adult patients with chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5 years and were monitored for YMDD-variant HBV, hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine aminotransferase (ALT) concentrations. Four-year data are reported here. Results: The rate of HBeAg seroconversion increased with extended therapy and also with higher baseline ALT concentrations. YMDD-variant HBV was detected in 67% (39/58) of patients at some point during treatment. After 4 years, a total of 47% (27/58) of patients achieved HBeAg seroconversion. Thirty-three per cent (13/39) of patients with YMDD-variant HBV achieved HBeAg seroconversion; this increased to 57% (8/14) in patients with moderately elevated (>2–5 × upper limit of normal) pre-treatment ALT concentrations. The proportion of patients that achieved normal serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years of treatment. That included 68% (23/34) of patients with YMDD-variant HBV and 73% (8/11) of those without the variant. All patients receiving lamivudine had reduced serum concentrations of HBV-DNA compared with baseline, despite the emergence of YMDD-variant HBV in 39 patients. Lamivudine was generally well tolerated; there was little change in the number or type of drug-related adverse events in the fourth year of the study. Conclusions: Despite the emergence of YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine.

The pathogenesis of focal nodular hyperplasia of the liver

Abstract: The pathogenesis of focal nodular hyperplasia is poorly understood. The lesion has been reported adjacent to many other focal hepatic lesions suggesting this is a nonspecific reaction to injury. Recent evidence suggests that arterio-venous shunt formation may trigger a positive feedback loop that includes hepatocellular hyperplasia.

Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area.

Abstract: Aim: To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally. Methods: We conducted a retrospective study which involved 145 multiple transfused patients and 250 healthy controls. A prospective study was also undertaken involving 50 hospitalized patients, 25 of whom were transfused with 107 blood units, while the other 25 did not receive any transfusions. Results: In our retrospective study, markers of acute HEV infection (IgM anti-HEV and HEV RNA) were detected in a significantly higher number of multiple transfused patients (13 of 145) compared to controls (two of 250) (P < 0.001; OR = 12.21 [95% confidence interval: 2.71–54.70]). All 13 HEV-infected patients had been transfused at least once in a 3-month period before testing. Overall, patients positive for any of the HEV markers (IgG, IgM or HEV RNA) had received more blood transfusions, had higher occurrence of icteric disease and higher serum alanine aminotransferase levels. In our prospective study, IgG anti-HEV was detected in 11 of 107 donor samples, three of 25 patients in their pretransfusion samples (one sample was positive for IgM anti-HEV as well) and two of 25 control patients. Post-transfusion HEV infection developed in three of 22 susceptible (IgG anti-HEV negative) transfused patients; the infection was traced to their four respective donors who were asymptomatic, HEV RNA positive (4/4) and IgM anti-HEV positive (3/4). In contrast, none of the non-transfused patients developed HEV infection during the follow-up period. Conclusion: Frequent transmission of HEV by blood transfusion places recipients at risk and warrants redefining of the donor screening policy by blood banks, especially in endemic areas.

Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men.

Abstract: Background and Aim: Although insulin resistance is often considered the link between obesity and non-alcoholic fatty liver disease (NAFLD), the role of insulin resistance, independent of obesity, as a NAFLD risk factor in non-obese men has been less well established. Systemic inflammation may be accompanied by insulin resistance in healthy subjects. The goal of the present study was to examine if insulin resistance and systemic inflammatory markers are independent predictors of NAFLD in non-obese men. Methods: The authors conducted a cross-sectional survey of 120 patients with NAFLD and 240 controls matched by age and body mass index. Controls had no evidence of alcohol abuse, hepatitis B or C, obesity, or previous history of diabetes, fasting hyperglycemia or hypertension. Diagnosis of NAFLD was based on an elevated alanine aminotransferase level and sonographic evidence of a fatty liver. Insulin resistance was determined using a homeostasis model assessment (HOMA-IR). Results: The age-adjusted risk of developing NAFLD was strongly associated with the elevated levels in measurements of uric acid, fasting blood sugar, triglycerides, apolipoprotein B, C-reactive protein (CRP) and HOMA-IR, and decreased levels of high density lipoprotein cholesterol and apolipoprotein A-I. Multivariate analysis based on univariate analysis indicated that an increase in CRP (odds ratio [OR] = 1.37; 95% confidence interval [CI]: 1.06–1.77) per 1 SD (1.48 mg/L) and HOMA-IR (OR = 2.28; 95% CI: 1.67–3.11) per 1 SD (0.63) were independent risk factors for NAFLD. Conclusion: Insulin resistance and systemic inflammatory response are of key importance for inducing NAFLD, particularly in apparently healthy non-obese men.

Survey on chronic pancreatitis in the Asia-Pacific region.

Abstract: Background and Aims: A survey was conducted of chronic pancreatitis (CP) in different countries in the Asia–Pacific region. The main objective of the survey was to generate a database containing information regarding the prevalence, etiology, clinical presentation, diagnostic work-up, and management of CP in the Asia–Pacific region. Methods: Data were collected from seven countries using a structured questionnaire. Expert participants were asked to respond to the questionnaire based on the data of patients with CP studied in their centers. Results: The prevalence of CP was found to be very high in southern India (114–200/100 000 population), in contrast to the low reported rate of 4.2/100 000 population in Japan. Alcohol was the most common etiological factor in Australia (95%) and Japan (54%) while idiopathic pancreatitis was the most common type in India (tropical pancreatitis) and China, accounting for approximately 70% of all cases of CP. Pain was the most common clinical feature. Diabetes and steatorrhea were uncommon. With regard to the diagnosis of CP, all the experts believed that a patient could be diagnosed as having CP in the presence of any one or more of the following: ductal changes on endoscopic retrograde cholangiopancreatography, a positive secretin test, pancreatic calcification, and endosonographic abnormalities suggestive of CP. Most experts suggested pancreatic enzymes and analgesics as initial medical therapy for pain relief in CP. Endotherapy was suggested as the therapy of choice if medical therapy failed. Surgery was offered only after the failure of endotherapy. Most experts agreed that research should focus on genetic abnormalities in CP and the role of endotherapy for pain relief. Conclusion: The survey brought out the prevalent types and presentation of CP, common management practices, and also the shortcomings in the existing knowledge of CP in the Asia–Pacific region. These findings might help focus attention on the research priorities for CP in this region.

Hepatic venous outflow tract obstruction etiopathogenesis: Asia versus the West

Abstract: There are three possible levels of obstruction to the hepatic venous blood outflow: the small intrahepatic veins, the large hepatic veins and the suprahepatic portion of inferior vena cava (IVC). Although some cardiac and pericardial diseases may result in an impaired hepatic venous outflow, these diseases are excluded from the entity thereafter referred to as hepatic outflow tract obstruction (HVOTO). Also excluded from HVOTO is the entity formerly known as venoocclusive disease and recently renamed sinusoidal obstruction syndrome. The latter denomination accounts for the fact that the primary event is a toxic injury to sinusoidal endothelium, followed by a secondary sinusoidal outflow block from embolization of cellular debris in the central area of the lobule. Therefore, although sinusoidal obstruction syndrome shares many pathophysiological, clinical and laboratory features with HVOTO, it markedly differs from the latter by the context and the causes (conditioning for stem cell transplantation or ingestion of pyrrolizidine alkaloids), the course and the treatment. Recently, a panel of European experts including this author recommended that the disease resulting from HVOTO, as defined above, be called Budd–Chiari syndrome. However, other authors advocated that the terms Budd–Chiari syndrome be abandoned, or restricted to pure hepatic vein thrombosis. For the sake of clarity, this term will not be used as an equivalent for HVOTO in the present overview. HVOTO related to compression or invasion by a spaceoccupying lesion will not be considered in the following. Compression of the inferior vena cava by an enlarged caudate lobe will not be considered either. A schematic view has long opposed the characteristics of HVOTO occurring is Asia to those of HVOTO encountered in western countries. As presented in Table 1, the features opposing the two areas would be: (i) the level of HVOTO; (ii) the nature of obstructive lesions; (iii) the presentation and course of the disease; and (iv) its causes. The purpose of this overview is to critically examine these four issues.

Non-alcoholic steatohepatitis in the Asia-Pacific region: future shock?

Abstract: Clinicians in both the developed and also the newer industrial economies in the Asia-Pacific region will encounter non-alcoholic fatty liver disease (NAFLD) with increasing frequency. Although the region has been a significant contributor to the current state of knowledge, the spectrum of NAFLD, its severity and the potential for significant future morbidity and health costs are not widely recognized. Lifestyle changes, the epidemic of childhood and adult obesity and type 2 diabetes sweeping the Asia-Pacific represent the key substrates for the rising prevalence of NAFLD. Physicians in all disciplines need to be aware of clinical clues to the presence of NAFLD in the absence of other liver disease and in those with chronic viral hepatitis and they should be able to identify subsets at risk for liver-related morbidity. Given the scope of the problem, efforts should focus primarily on preventing or ameliorating the impact of risk factors; the key one is insulin resistance and its associates of diabetes and central obesity. Pharmacotherapy may play a role in selected individuals. A regional agenda for case definition, future study and public health initiatives is urgently required.

Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease.

Abstract: Background and Aims: The adverse effect of acute hepatitis A in chronic liver disease is well known. The outcome of acute hepatitis E in chronic liver disease has not been extensively studied. The present study aimed to examine the clinical profile and outcome of patients with chronic liver disease and hepatitis E virus (HEV) superinfection, and the seroprevalence of hepatitis A and E infections in patients with chronic liver disease and controls in India. Methods: A retrospective study of patients with chronic liver disease and acute icteric hepatitis E was performed. Acute hepatitis E was diagnosed by immunoglobulin (Ig)M ELISA. Seroprevalence studies were carried out using IgG ELISA in 100 patients with chronic liver disease and 79 age- and sex-matched controls. Results: From June 2001 to December 2002, nine patients with chronic liver disease were found to have superinfection with HEV. Out of these, six patients died of advanced liver failure. The etiology of liver disease was Wilson's disease in six, hepatitis B virus in one, autoimmune in one and cryptogenic in one case. The seroprevalence of hepatitis A was 99 and 100% and 56 and 21% for HEV in cases and controls, respectively. Conclusions: Acute HEV in patients with chronic liver disease has a grave prognosis. Wilson's disease was the most common cause of chronic liver disease complicated by acute HEV. Seroprevalence studies showed that 44% of patients with chronic liver disease were at risk of developing hepatitis E. Hepatitis E vaccine, when available, is indicated for use in this group.

Lactobacillus plantarum 299: Beneficial in vitro immunomodulation in cells extracted from inflamed human colon

Abstract: BACKGROUND AND AIM The present study determined the pattern of cytokine secretion (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma and IL-10) and their cellular sources in mononuclear cells isolated from colonic mucosa from normal and ulcerative colitis (UC) in response to probiotic and pathogenic bacteria. METHODS Mononuclear cells were extracted from normal and active UC colonic mucosa and incubated with pure sonicates of probiotic, commensal, and pathogenic bacteria. Cytokine secretion was measured in culture supernatant and intracellular cytokine staining measured using fluorescent-activated cytometry. RESULTS In mononuclear cells isolated from normal mucosa, significant increases in mean IL-1beta were observed with enteropathogenic Escherichia coli (286.3 +/- 138.7 pg/mL P < 0.05) and E. coli (440.5 +/- 194.0 pg/mL P < 0.01) compared with unstimulated control cells (16.7 +/- 4.8 pg/mL). In contrast, mononuclear cells isolated from active UC mucosa produced significant increases in mean IL-1beta in response to stimulation with Salmonella dublin (230.5 +/- 38.8 pg/mL P < 0.05), enteropathogenic E. coli (231.7 +/- 45.3 pg/mL P < 0.05) and E. coli (465.4 +/- 60.2 pg/mL P < 0.001) compared with unstimulated control cells (60.7 +/- 17.1 pg/mL). Escherichia coli also produced significant mean increases of TNF-alpha and IFN-gamma compared with unstimulated control cells. No significant increases in IL-1beta, TNF-alpha or IFN-gamma were observed with Lactobacillus plantarum in cells derived from normal or inflamed mucosa. Strikingly, incubation of L. plantarum with mononuclear cells isolated from active UC mucosa resulted in significant increases of mean IL-10 (327 +/- 53.5 pg/mL, P < 0.05) compared with unstimulated control cells (29.7 +/- 13.2 pg/mL). Intracellular cytokine staining confirmed T-cell and macrophage IL-10 production after L. plantarum stimulation. CONCLUSIONS Lactobacillus plantarum demonstrates beneficial immunomodulatory activity by increasing IL-10 synthesis and secretion in macrophages and T-cells derived from the inflamed colon. This may provide a mechanism through which probiotic bacteria ameliorate inappropriate inflammation and induce tolerance.

Digital quantification of fibrosis in liver biopsy sections: Description of a new method by Photoshop software

Abstract: Background: The precise quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease, as well as in evaluating the response to antifibrotic therapy. Because the recently described methods of digital image analysis of fibrosis in liver biopsy sections have major flaws, including the use of out-dated techniques in image processing, inadequate precision and inability to detect and quantify perisinusoidal fibrosis, we developed a new technique in computerized image analysis of liver biopsy sections based on Adobe Photoshop software. Methods: We prepared an experimental model of liver fibrosis involving treatment of rats with oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a series of computer operations were performed including (i) reconstitution of seamless widefield images from a number of acquired fields of liver sections; (ii) image size and solution adjustment; (iii) color correction; (iv) digital selection of a specified color range representing all fibrous tissue in the image and; (v) extraction and calculation. Results: This technique is fully computerized with no manual interference at any step, and thus could be very reliable for objectively quantifying any pattern of fibrosis in liver biopsy sections and in assessing the response to antifibrotic therapy. It could also be a valuable tool in the precise assessment of antifibrotic therapy to other tissue regardless of the pattern of tissue or fibrosis.

Intralesional steroid injection in benign esophageal strictures resistant to bougie dilation

Abstract: Objective: Some benign esophageal strictures are highly resistant to bougie dilation. The aim of this study was to determine whether intralesional steroid injection had additional benefit to Savary-Gilliard’s bougie dilation therapy (SGBD). Methods: Twenty-one patients were treated with a bougie dilator. The patients were randomized into control and study groups. There were 11 patients in the control group (7 males, 4 females; mean age 45.09 ± 24.64 years) and 10 patients in the study group (4 males, 6 females; mean age 49.40 ± 16.49 years). The patients in the control group underwent only SGBD, but patients in the study group received an additional intralesional steroid injection (8 mg triamcinolone acetate into each quadrant). The number of dilations was divided by the follow-up period (in months) to determine the periodic dilatation index. Results: There was no difference in age, sex, etiology, localization and recurrence of lesions, treatment outcome, complications and the number of dilations between the study and control groups. In the study group, the mean periodic dilatation index was 0.712 (range 0.097‐2.75) and 0.289 (range 0‐1) before and after injections, respectively (P = 0.03). Additionally, the mean number of dilations was 5.3 (range 2‐11) and 1.6 (range 0‐5) before and after injections, respectively (P = 0.03). The mean symptom-free interval was 24 ± 12.75 months in the study group and 5.18 ± 5.06 months in the control group (P < 0.001). The total periodic dilatation index was 0.193 ± 0.123 in the study group, while it was 0.597 ± 0.583 in the control group (P < 0.05). Conclusions: It can be concluded that intralesional steroid injections increase efficacy of bougie dilation and decrease the requirement for repetition of bougie dilatation. © 2004 Blackwell Publishing Asia Pty Ltd

Risk behaviors and antibody hepatitis B and C prevalence among injecting drug users in south‐western Sydney, Australia

Abstract: Background and Aim: Hepatitis C virus (HCV) infection is now the leading notifiable disease in Australia. The current study aimed to determine the prevalence of HCV and hepatitis B virus (HBV) infection and associated risk behaviors among injecting drug users (IDUs) screened in south-western Sydney as part of a multisite prospective cohort study. Methods: Using a combination of snowball sampling and word-of-mouth recruitment strategies, 377 IDUs were interviewed using a structured questionnaire and tested for exposure to HCV and HBV. Entry criteria were injecting drug use in the previous 6 months and antibody HCV serostatus not known to be positive. Results: More than one-third (36.6%) tested HCV antibody positive and one-quarter (28%) had been exposed to HBV. Independent predictors of HCV seropositivity were HBV core antibody positive serostatus, incarceration in the past year, injecting in public, Asian ethnicity and duration of injecting. Individual risk behaviors, including sharing needles and syringes, sharing other injecting equipment and being injected by others, were not significant in either bivariate or multivariate models. Conclusions: Results indicate an urgent need for structural interventions designed to reduce the exposure of IDUs, particularly indigenous Australian and Asian injectors, to risk environments. Structural interventions, including population-based hepatitis B immunization, expanded access to needle and syringe programs and drug treatment, prison diversion programs and medically supervised injecting facilities, should be incorporated into existing blood-borne virus prevention efforts.

Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic prevalence, histological and clinical characteristics.

Abstract: Background and Aim: Heterotopic gastric mucosal patch, which has a 0.1–10% frequency, is encountered when the cervical esophagus is examined carefully during endoscopy. In this study, we aimed to determine the prevalence of the patch in the cervical esophagus, to identify its macroscopic and histological characteristics and to evaluate demographic and clinical features. Methods: Six hundred and sixty patients (317 male, 343 female; mean age 50.28 years, range 14–90) with upper gastrointestinal symptoms had elective esophagogastroduodenoscopy and the cervical esophagus was examined for the patch during withdrawal of the endoscope. Biopsies were obtained from the antrum and the patch. Helicobacter pylori was assessed using an immunohistochemical method. Results: The patch was found in 11 patients of 660, with a prevalence of 1.67%. Patch size ranged between 5 and 30 mm, appeared as a single patch in nine patients and as twin patches in two patients. Mean age and male : female ratio were not significantly different from the patient population without patches, but the female sex was predominant (three men, eight women; mean age 43.6 years, range 32–64). In five of 11 patients, the upper esophageal and laryngopharyngeal symptoms were remarkable. Eight patients in whom histological confirmation was carried out showed three fundic and five antral-type mucosa. Two of five patients with antral H. pylori also had the bacteria in the patch. H. pylori prevalence in the patch was 25%. Conclusion: Heterotopic gastric mucosal patches in the proximal esophagus should not be overlooked during endoscopy because they may lead to important complications in relation to their acid secretion, which may vary according to their parietal cell mass.

Report of the Asia–Pacific consensus on the management of gastroesophageal reflux disease

Abstract: This report summarizes the conclusions and recommendations of a panel of gastroenterologists practising in the Asia-Pacific region. The group recognized that although gastroesophageal reflux disease (GERD) is less common and milder in endoscopic severity in Asia than in the West, there is nevertheless data to suggest an increasing frequency of the disease. During a 2-day workshop, the evidence for key issues in the diagnosis and clinical strategies for the management of the disease was evaluated, following which the recommendations were made and debated. The consensus report was presented at the Asia-Pacific Digestive Week 2003 in Singapore for ratification. Upper gastrointestinal (GI) endoscopy is the gold standard for the diagnosis of erosive GERD. There is no gold standard for the diagnosis of non-erosive GERD (NERD). Diagnosis therefore relies on symptoms, a positive 24-h pH study or a response to a course of proton pump inhibitor (PPI) treatment. The goals of treatment for GERD are to heal esophagitis, relieve symptoms, maintain the patient free of symptoms, improve quality of life and prevent complications. The PPI are the most effective medical treatment. Following initial treatment, on-demand therapy may be effective in some patients with NERD or mild (GI) erosive esophagitis. Anti-reflux surgery by a competent surgeon could achieve a similar outcome, although there is an operative mortality of 0.1-0.8%. The decision is dependent on the patient's preference and the availability of surgical expertise. Currently, endoscopic treatment should be performed only in the context of a clinical trial. Treatment of patients with typical GERD symptoms without alarm features in primary care could begin with PPI for 2 weeks followed by a further 4 weeks before going to on-demand therapy.

High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection

Abstract: Background and Aims: Hepatitis B virus (HBV) is considered a major risk factor for the progression to liver cirrhosis and hepatocellular carcinoma (HCC). The serum level of HBV-DNA is correlated with progression of the disease. The aim of the present study was to determine the relationship between the level of HBV-DNA and hepatocarcinogenesis in patients with chronic HBV infection. Methods: The authors studied 73 patients who were diagnosed with chronic HBV infection at Nagasaki University Hospital (Nagasaki, Japan) between January 1980 and December 1999. The significance of age, sex, habitual drinking, serum alanine aminotransferase level, HBV viral load, interferon treatment, hepatic fibrosis and hepatic inflammation on the development of HCC were examined using univariate and multivariate analyses. Results: The cumulative incidence rates of HCC were 14%, 29% and 48% at 5, 10 and 15 years after liver biopsy, respectively. Multivariate analysis identified high viral load, together with age and severe fibrosis, as independent and significant risk factors (P = 0.045, 0.047 and 0.013, respectively) for HCC. Conclusions: The present findings indicate that high viral load is a risk factor for HCC in patients with chronic HBV infection. Patients with a high HBV viral load should be carefully monitored for HCC.

Cost-effectiveness of colorectal cancer screening: comparison of community-based flexible sigmoidoscopy with fecal occult blood testing and colonoscopy.

Abstract: Background and Aims: To determine the cost-effectiveness of screening for colorectal cancer using flexible sigmoidoscopy once every 10 years, compared with annual and biennial rehydrated Hemoccult fecal occult blood testing and colonoscopy once every 10 years, or no screening. Methods: A Markov model was developed in order to simulate the progression of a cohort of asymptomatic, average-risk individuals aged 55–64 years who were moving through a defined series of states towards death. The main outcome measures were: cases of colorectal cancer averted, colorectal cancer deaths averted, and cost per life-year saved. Results: Colonoscopy averted the greatest number of cases of colorectal cancer (35%), followed by flexible sigmoidoscopy (25%), and annual (24%) and biennial (14%) fecal occult blood testing. Colonoscopy averted the greatest number of deaths from colorectal cancer (31%), followed by annual fecal occult blood testing (29%), flexible sigmoidoscopy (21%) and biennial fecal occult blood testing (19%). Flexible sigmoidoscopy was the most efficient in terms of cost per life-year saved (A$16 801), followed by colonoscopy (A$19 285), biennial (A$41 183), and annual (A$46 900) fecal occult blood testing. Conclusions: Flexible sigmoidoscopy and colonoscopy are cost-effective strategies for reducing the disease burden of colorectal cancer.

Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects.

Abstract: Background and Aim: Numerous mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with familial unconjugated hyperbilirubinemia. The UGT1A1 mutation appears to be considerably different among ethnic groups. To clarify the incidence of this gene mutation in the Japanese population, the presence of UGT1A1 mutation was investigated in a group of Japanese patients with Crigler–Najjar syndrome type 2 (CNS2) and Gilbert's syndrome (GS), as well as in healthy anicteric subjects. Methods: Four patients with CNS2, 63 patients with GS, and 71 healthy subjects were enrolled in the study. The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. The PCR products were directly sequenced by a dye terminating method. The UGT1A1 enzyme activity was determined in COS7 cells transfected with wild or P364L (1091 C > T) mutant DNA. Results: Homozygous Y486D was observed in all four patients with CNS2. The GS patients had UGT1A1 mutations with 13 different genotypes in the promoter and coding region. Homozygous TA insertion in the TATA box (TA7) of the promoter region (TA7/7; 33%), homozygous G71R (9%), and combination of TA7/6 and heterozygous G71R (17%) were the most frequent findings in GS patients. Homozygous or heterozygous Y486D (8%) and P229Q (8%) were also observed in GS. A novel mutation, heterozygous P364L, was also identified in a GS patient. In addition to GS patients, homozygous or heterozygous TA7, G71R, and heterozygous Y486D were also observed in healthy subjects. The allele frequency of G71R and TA7 was 0.183 and 0.113 in healthy subjects, respectively. The P364L UGT1A1 enzyme activity was 64.4% lower than the wild-type enzyme activity. Conclusions: Polymorphisms in the coding region of UGT1A1 were commonly observed in Japanese patients with GS and in healthy subjects. The genetic basis of hyperbilirubinemia appears to be different between the Japanese and Caucasian populations.

Which patients benefit from hemodialysis therapy in hepatorenal syndrome

Abstract: Background and Aim: Hepatorenal syndrome (HRS) occurs in patients with advanced liver cirrhosis and has a poor outcome. The aim of the present study was to investigate which patients with HRS are likely to benefit from hemodialysis. Methods: Data were collected prospectively from 30 patients with Child-Pugh C liver cirrhosis and HRS. Patients were either treated with continuous veno-venous hemodialysis (CVVHD) if they were mechanically ventilated, or with intermittent hemodialysis (HD) if they were not mechanically ventilated. Prognosis was assessed by the Child-Pugh and by the Model for End-Stage Liver Disease (MELD) score. The primary aim of the study was the analysis of overall and 30-day patient survival during hemodialysis therapy. To identify predictive factors of survival, variables obtained before the initiation of dialysis therapy were evaluated. Results: Patients’ 30-day survival was 8/30 (median survival time 21 days). Among patients treated with mechanical ventilation, 30-day survival time was 0/15 while 8/15 patients without mechanical ventilation survived more than 30 days (P 0.05), indicating that these parameters were not independent predictors of survival. Mechanical ventilation was an independent risk factor for 30-day (relative hazard 6.6 [1.6–27.7], P < 0.001) and overall survival (relative hazard 6.3 [1.5–26.5], P = 0.01). Child-Pugh (P < 0.01) and the MELD (P < 0.01) score were predictive for overall survival independent of mechanical ventilation. Conclusions: Patients with HRS without mechanical ventilation may benefit from hemodialysis, whereas hemodialysis seems to be futile in patients with mechanical ventilation.

Gastrointestinal luminal tuberculosis: establishing the diagnosis.

Abstract: Background and Aim :T o study the profile of gastrointestinal luminal tuberculosis (GITB) patients who have been treated on a confirmed and a presumptive diagnosis. Methods :A total of 260 patients who had an initial diagnosis of GITB were included in this retrospective analysis. Clinical, radiologic, endoscopic, histopathologic and microbiologic features of these patients were studied in detail. Results: GITB was confirmed in 66.5% patients (cGITB), while 29.5% had presumed GITB (pGITB). In 3.9% patients, Crohn’s disease (CD) was misdiagnosed initially as GITB. There was no significant difference in the clinical and radiologic features except a higher incidence of a radiologically abnormal ileocecal region in cGITB patients. Endoscopic biopsies from ulcerated masses and ulcers had the highest yield of confirmation (100% and 68%, respectively) when subjected to histopathology, acidfast bacilli smear and culture studies. Confirmed diagnosis was obtained in 100% of cases occurring in the upper gastrointestinal tract, 66% of cases in the ileocecal region/colon and 40% of cases that had small bowel involvement. In 21% of cases, extraluminal sites helped to confirm the diagnosis. As the presence of diarrhea, bleeding, fistulae, perianal disease and extraintestinal manifestations favored a diagnosis of CD, the presence of these features initially or on subsequent follow up helped to minimize the misdiagnosis of GITB. Conclusions: As a differential diagnosis, CD must be ruled out before starting treatment for GITB. In our study, an intense search for histologic and microbiologic proof of the presence of TB from luminal and extraluminal sites established the diagnosis in 66.5% of cases. Surgery for establishing the diagnosis should be reserved for complicated cases. © 2004 Blackwell Publishing Asia Pty Ltd

Leptin levels in the acute stage of ulcerative colitis.

Abstract: Background and Aims: Leptin, a recently discovered protein, acts as a hormonal feedback signal in regulating adipose tissue mass via hypothalamic mechanisms. Inflammatory bowel disease is often associated with anorexia and weight loss. The aim of the present study was to investigate serum leptin levels during the time course of the acute phase of ulcerative colitis (UC) and to evaluate whether leptin leads to anorexia and bodyweight loss in these patients. Methods: Serum leptin levels of 29 male patients with acute UC and 17 healthy controls with similar age, sex and body mass index (BMI) were measured. Erythrocyte sedimentation rate (ESR), BMI, serum albumin and C-reactive protein concentrations, and white blood cell counts were determined. Results: A significant increase in serum leptin levels was found in patients with acute UC when compared with controls (5.89 ± 2.06 ng/mL and 3.64 ± 1.69 ng/mL, respectively; p = 0.001). There was no correlation between leptin levels and BMI. Conclusions: Our findings in the acute stage of UC suggest that increased serum leptin levels may contribute to anorexia and weight loss. However, an inappropriate increase in leptin levels is independent of body mass in acute UC, and we believe that other factors may be involved in inflammation-induced increases in leptin levels.

Changing epidemiology of gastroesophageal reflux disease in the Asian-Pacific region: an overview

Abstract: Gastroesophageal reflux disease (GERD) is a common disease in the West, which now appears to be also increasing in prevalence in the Asian Pacific region. The reasons for this changing epidemiology are two-fold: an increased awareness among doctors and patients, and/or a true increase in the prevalence of the disease. Prevalence rates of reflux esophagitis (RE) of up to 16% and prevalence of GERD symptoms of up to 9% have been reported in the Asian population. However, the frequency of strictures and Barrett's esophagus remain very low. Non-erosive reflux disease (NERD) appears to be the most common form of GERD among Asian patients accounting for 50-70% of cases with GERD. Among Asian patients differences can also be discerned among different ethnic groups. For example, in Malaysia where a multiracial society exists, RE is significantly more common among Indians compared to Chinese and Malays whereas NERD is more frequently seen in the Indian and Malays compared to the Chinese. The reasons for these differences are not known but may indicate both genetic factors and environmental factors peculiar to the particular racial group. GERD has also been increasing in the region demonstrating a time-lag phenomenon compared to the West. Differing predisposition to GERD among different ethnic groups would mean that such an increase would be more prominent among certain racial groups.

Infrequency of colonization with Oxalobacter formigenes in inflammatory bowel disease: possible role in renal stone formation.

Abstract: Background and Aim: Calcium oxalate renal stones (RS) and hyperoxaluria are common in patients with inflammatory bowel disease (IBD). The absence of intestinal oxalate degrading bacteria, Oxalobacter formigenes, may cause hyperoxaluria in IBD. The aim of the present study was to examine: (i) the colonization of O. formigenes in patients with IBD and controls and to correlate its presence with urinary oxalate excretion; and (ii) urinary analytes contributing to RS in IBD. Methods: Stool samples were studied for O. formigenes using polymerase chain reaction and Southern blotting in patients with IBD (n = 48: ulcerative colitis, 37; Crohn's disease, 11), RS (n = 87) and healthy subjects that were used as controls (n = 48). Levels of urinary oxalate, citrate, calcium, magnesium, creatinine and uric acid were estimated spectrophotometrically in each patient and in 13 controls for 24 h. Results: Five of the 48 (10.4%) patients with IBD had RS. Five of the 48 (10.4%) patients with IBD, 25 of the 87 (29%) with RS and 27 of the 48 (56%) controls were colonized with O. formigenes (P < 0.001 for RS vs controls and P = 0.01 for RS vs IBD). Patients without O. formigenes had higher urinary oxalate than those with it (IBD, median 0.48 [range 0.11–2.09]vs 0.43 [range 0.16–1.10] mmol/24 h, P = NS; RS, median 0.59 mmol/24 h, range 0.14–1.90 vs 0.44 mmol/24 h, range 0.23–0.97; P = 0.008, Mann–Whitney U-test). Median excretion of oxalate was higher in IBD and RS than in controls (0.47 [0.11–2.09], 0.56 [0.14–1.9] and 0.41 [0.21–0.62] mmol/24 h; P < 0.01), respectively. Median calcium was also higher in IBD and RS than in controls (6.50 [1.38–21.00], 6.78 [1.55–20.30] and 4.99 [1.47–9.60] mmol/24 h; P < 0.05, Kruskal–Wallis H-test), respectively. Median urinary magnesium was higher in IBD than in RS and controls (4.57 [1.50–12.30], 3.60 [0.90–6.35] and 2.49 [0.74–4.80]; P < 0.001, Kruskal–Wallis H-test), respectively. Urinary citrate excretion was comparable in IBD, RS and controls. Conclusions: Patients with IBD and RS rarely have O. formigenes in their stools as compared with controls; this may contribute to hyperoxaluria in IBD. Hyperoxaluria and hypercalciuria may contribute to RS in patients with IBD. Hypermagnesuria in patients with IBD may protect them from RS.

Factors contributing to ribavirin‐induced anemia

Abstract: Background and Aim: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia. Methods: Eighty-eight patients with chronic hepatitis C who received interferon-α-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of <10 g/dL was defined as ribavirin-induced anemia. Results: Ribavirin-induced anemia occurred in 18 (20.5%) patients during treatment. A 2 g/dL decrease in hemoglobin concentrations in patients with anemia was observed at week 2 after the start of treatment. The hemoglobin concentration in patients with ≥2 g/dL decrease at week 2 was observed to be significantly lower even after week 2 than in patients with <2 g/dL decrease (P < 0.01). A significant relationship was observed between the rate of reduction of hemoglobin concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as sex (female), age (≥60 years old), and the ribavirin dose by body weight (12 mg/kg or more) were significant by univariate analysis. Conclusions: Careful administration is necessary in patients ≥60 years old, in female patients, and in patients receiving a ribavirin dose of 12 mg/kg or more. Patients who experience a fall in hemoglobin concentrations of 2 g/dL or more at week 2 after the start of treatment should be monitored with particular care.

Clinical manifestations of sarcoid liver disease.

Abstract: Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves many organs and has different clinical manifestation. We reviewed the clinical manifestations of sarcoid liver disease. Liver involvement in sarcoidosis can be serious and life-threatening, independent of its lung and other organ involvement.

Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B.

Abstract: Background: Severe acute exacerbations of chronic hepatitis B virus (HBV) infection can spontaneously occur and rapidly progress to fatal hepatic failure. The purpose of the present paper was to identify factors that could influence the rapid progression of liver disease to hepatic failure, and assess the effects of lamivudine on serious disease. Methods: Twenty-five patients with spontaneous severe acute exacerbation (accompanied by jaundice and coagulopathy) were consecutively treated with lamivudine. Their clinical outcomes were compared with those of 25 lamivudine-untreated patients, as historical controls. Results: Six lamivudine-treated patients (24%)and seven controls (28%) rapidly developed hepatic failure. Lamivudine monotherapy did not significantly prevent progression to hepatic failure. Multivariate analysis identified baseline serum bilirubin ≥6 mg/dL (odds ratio [OR]: 5.61; 95% confidence interval [CI]: 1.66–21.61; P = 0.018), pre-existing cirrhosis (OR: 4.52; 95%CI: 1.26–30.42; P = 0.034), and baseline prothrombin time 0.15). However, lamivudine induced a sustained normalization of liver function and inhibited the development of cirrhosis in survivors. Conclusions: Lamivudine monotherapy conferred no significant protection against rapid progression of the disease to hepatic failure, but it resulted in long-term benefits. Lamivudine combined with other drugs could be more beneficial for patients with the aforementioned risk factors. © 2004 Blackwell Publishing Asia Pty Ltd

Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection.

Abstract: Background: Increased serum γ-glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV-infected carriers. Methods: Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the χ2 test and multivariate logistic regression analysis. Results: Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Inititally, age > 40 years (P = 0.007), elevated ALT (P = 0.01), grading of inflammatory activity (P = 0.004) and staging of fibrosis (P < 0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P = 0.01) and staging 3 and 4 fibrosis (P = 0.01) remained independently associated with elevated GGT level. Conclusions: A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C. © 2004 Blackwell Publishing Asia Pty Ltd

Immunoactivative role of indoleamine 2,3-dioxygenase in human hepatocellular carcinoma.

Abstract: Background: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme. Recent studies have focused on the immunoregulatory role of IDO in mononuclear cells. The role of IDO in hepatocellular carcinoma (HCC) cell lines and HCC patients was examined. Methods: The expression of IDO mRNA in peripheral blood mononuclear cells (PBMC) cocultured with HCC cell lines was detected by reverse transcriptase–polymerase chain reaction (RT-PCR). The cytotoxicity of PBMC against HCC cell lines cultured with and without IDO inhibitor was examined by sodium 51chromate release assay. In the tumor portion of 21 HCC patients, the expression of mRNA of IDO, tryptophan 2,3-dioxygenase and some cytokines was detected by RT-PCR. The expression and distribution of IDO protein in HCC specimens was analyzed by immunohistochemistry. Results: The IDO mRNA was strongly induced in PBMC cocultured with HepG2 and PLC/PRF/5 and faintly induced in PBMC cocultured with Hep3B and HuH7. The cytotoxicity of PBMC against HCC cell lines was directly proportional to the level of expression of IDO mRNA and reduced by IDO inhibitor. The expression of IDO mRNA in the tumor portion was detected in 12 out of 21 HCC patients. Immunohistochemistry revealed that the IDO-positive cells were identified to be tumor-infiltrating cells, not tumor cells. The IDO mRNA correlated significantly with gene expression of interferon-γ, tumor necrosis factor-α and interleukin-1β. The recurrence-free survival rate of IDO-positive HCC patients was significantly higher than that of IDO-negative HCC patients (P < 0.05). Conclusions: These results suggest that IDO is a necessary enzyme for anticancer immune reactions of tumor-infiltrating cells. © 2004 Blackwell Publishing Asia Pty Ltd