Showing papers in "Journal of Gastroenterology and Hepatology in 2001"

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis.

Abstract: Background and Aims: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. Methods: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6–8 week intervals. Results: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of ≤ 6 (40 vs 5%, P = 0.019). Conclusions: We conclude that SHE is common in cirrhosis. The natural history of SHE is worse in patients with advanced cirrhosis and SHE probably predisposes the cirrhotic patient to overt hepatic encephalopathy.

Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase M1 'null' mutation

Abstract: Background: Pathogenesis and genetic factors influencing predisposition to antituberculosis drug (ATD)-induced hepatotoxicity are not clear. Polymorphism at the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N-acetyltransferase type 2 (NAT2), is reported to be associated with the excess generation of toxic reactive metabolites. Polymorphisms at the glutathione S-transferase (GST) loci (GSTM1 and GSTT1) are involved in the detoxification of these toxic metabolites in the human body to a lesser extent. We have examined whether polymorphisms at these loci are associated with the risk of ATD-induced hepatotoxicity. Methods: In this case-control study, 33 pulmonary tuberculosis patients with ATD-induced hepatotoxicity and 33 pulmonary tuberculosis patients receiving ATD drugs without any evidence of hepatotoxicity were considered as cases and controls, respectively. Point mutations at NAT2 and homozygous ‘null’ mutations at GSTM1 and GSTT1 genes were looked into genomic DNA, isolated from peripheral blood mononuclear cells by using polymerase chain reaction (PCR). Results: The frequency of homozygous ‘null’ mutation at the GSTM1 gene was significantly higher among cases (n = 17, 52%) than controls (n = 8, 24%) (P < 0.05, relative risk 2.13, 95% CI: 1.25–3.10). Frequencies of mutations at GSTT1 and NAT2 genes did not differ significantly between cases and controls. Conclusion: Homozygous ‘null’ mutation at the GSTM1 gene might predispose an individual to ATD-induced hepatotoxicity.

Hepatic steatosis in chronic hepatitis C virus infection: Prevalence and clinical correlation

Abstract: Background and aims Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. Methods One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV-RNA titer and histological findings, were compared between patients with and without hepatic steatosis. Results Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and gamma-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 +/- 1.2 vs 1.3 +/- 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of > or = 2. Conclusion It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis.

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.

Abstract: Background: Measurement of serum α-fetoprotein (AFP) and abdominal ultrasound (US) examination are used for the early detection of hepatocellular carcinoma (HCC) in chronic liver disease patients. However, the accuracy and usefulness of these tests in a clinical setting in the United States of America have not been clarified. Methods: We conducted a 7-year prospective surveillance study by using both AFP and US to detect HCC in 602 patients with chronic viral hepatitis. Our main goal was to determine the optimal test for detection of early HCC. We also assessed the clinical outcome of HCC patients identified during this time period. Results: Thirty-one cases of HCC were detected. Serum AFP levels were elevated in 74% of HCC patients, but was also high in 10% of patients who did not develop HCC. The positive predictive value for AFP to detect HCC was only 12% or less for all AFP cut-off values, and the maximum joint sensitivity and specificity as determined by receiver operator characteristic analysis was approximately 65 and 90%, respectively. Abdominal US identified all 31 cases of HCC. The positive predictive value for US examinations to detect HCC was 78%, while the sensitivity and specificity was 100 and 98%, respectively. After detection of HCC, 24 (77%) patients died within a mean of 16.7 ± 19.4 months. Conclusions: Our study indicates that US examination was more accurate in detecting HCC. Because of its poor predictive value and low sensitivity, serum AFP should not be used as the only test for screening and surveillance for HCC.

Benign nodular hepatocellular lesions caused by abnormal hepatic circulation: etiological analysis and introduction of a new concept.

Abstract: Problems in definitive diagnosis and etiology of various benign nodular hepatocellular lesions were evaluated. Of these lesions, focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), nodular lesions associated with idiopathic portal hypertension (IPH), non-cirrhotic large regenerative nodules (LRN), hepatocellular adenoma (HA)-like hyperplastic nodules, and partial nodular transformation (PNT) have been suggested to be related to abnormal hepatic circulation. However, the following points are considered to need further clarification: (i) is the abnormal circulation caused by thrombosis, vasculitis, or congenital anomaly?; (ii) is thrombosis a cause or a result of congestion?; (iii) are impaired blood vessels primarily the portal veins or arteries?; (iv) how are these disorders related to various syndromes, immunological abnormalities and abnormal blood flow of other organs, which are reported to coexist with these lesions often?; and (v) how should non-typical cases, which differ from typical cases, be interpreted? In addition, a concept that may lead to solving these problems (anomalous portal tract syndrome; a hypothesis that congenital vascular anomaly is the origin of these benign nodular hepatocellular lesions) was introduced.

Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury.

Abstract: Background and Aims: Hepatotoxicity, especially liver fibrosis, is the major concern with long-term, ‘low-dose’ oral methotrexate (MTX) therapy for psoriasis. The histological features are non-specific and resemble those of non-alcoholic steatohepatitis (NASH). Moreover, most of the risk factors of MTX-induced liver injury are also associated with NASH. In this study, we investigate whether NASH contributes to the prevalence and progression of MTX-induced liver injury in patients receiving MTX for psoriasis. Methods: Clinical details, including MTX dosage schedules and risk factors for liver injury, was documented for 24 patients on long-term MTX therapy for psoriasis. Serial liver biopsies were graded according to the Roenigk classification scale and a recently proposed grading and staging system for NASH. Results: Thirteen of the 17 patients who had a NASH-like pattern of liver injury also had the risk factors for NASH obesity and/or diabetes, and all had progressive liver injury. The other four patients had no risk factors, but a mean cumulative dose of 6.5 g. Seven patients, who did not have a NASH-like pattern of injury, had a mean cumulative dose of 3.8 g. There was a positive correlation between the cumulative dose, risk factors and progression when the biopsies were scored by the modified grading and staging classification for NASH, but not with the Roenigk system. Conclusions: Non-steatohepatitis, probably aggravated by MTX, is an important cause of liver injury in patients on long-term, ‘low-dose’ MTX treatment for psoriasis. In addition, MTX alone can cause a NASH-like pattern of injury that is at least, in part, caused by a higher cumulative dose.

Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea.

Abstract: Background:Helicobacter pylori infection occurs throughout the world and causes gastroduodenal diseases in all age groups. The prevalence of H. pylori infection varies between countries and races. The aim of this study was to evaluate the seroprevalence of H. pylori infection in asymptomatic healthy people in South Korea. Methods: From March 1998 to October 1998, 5732 asymptomatic subjects who responded to the self-assessment questionnaires from 54 hospitals in South Korea were enrolled in this study. The serum levels of antibodies for H. pylori immunoglobulinG were measured by using an ELISA test. Results: The overall seroprevalence of H. pylori infection was 46.6% and there was no statistical difference between males (47.2%) and females (45.9%). In adults, a significant difference was observed between genders. According to the geographic areas, the high prevalent provinces were Kangwon (53.4%), Cheju (52.9%) and Cholla province (50.6%); Seoul (41.9%) was the lowest prevalent area. The seroprevalence increased with age and was highest when patients were aged in their 40s (78.5%). The characteristic feature of our study was that the infection rate was steeply increased in three age groups (10–12 year olds, 16–19 year olds and those aged in their 20s). In Seoul, there was no difference in the prevalence rate among the districts studied. Conclusions: This nation-wide seroprevalence of H. pylori infection in South Korea was 46.6%, which showed the transition from a developing country to a developed country. More studies on the epidemiological factors and the route of transmission of H. pylori infection should be warranted.

Iron and hepatocellular carcinoma.

Abstract: The high prevalence of hepatocellular carcinoma (HCC) in genetic hemochromatosis (GH) and the association between increased body iron stores and occurrence of HCC in subjects with iron overload unrelated to GH, and the experimental evidence of a co-carcinogenic role of iron strongly support that iron is involved in the development of HCC.

Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3.

Abstract: Background and Aims: Hepatic steatosis has been shown to be associated with lipid peroxidation and hepatic fibrosis in a variety of liver diseases including non-alcoholic fatty liver disease. However, the lobular distribution of lipid peroxidation associated with hepatic steatosis, and the influence of hepatic iron stores on this are unknown. The aim of this study was to assess the distribution of lipid peroxidation in association with these factors, and the relationship of this to the fibrogenic cascade. Methods: Liver biopsies from 39 patients with varying degrees of hepatic steatosis were assessed for evidence of lipid peroxidation (malondialdehyde adducts), hepatic iron, inflammation, fibrosis, hepatic ;stellate cell activation (alpha-smooth muscle actin and TGF-beta expression) and collagen type I synthesis (procollagen a 1 (I) mRNA). Results: Lipid peroxidation occurred in and adjacent to fat-laden hepatocytes and was maximal in acinar zone 3. Fibrosis was associated with steatosis (P < 0.04), lipid peroxidation (P < 0.05) and hepatic iron stores (P < 0.02). Multivariate logistic regression analysis confirmed the association between steatosis and lipid peroxidation within zone 3 hepatocytes (P < 0.05), while for hepatic iron, lipid peroxidation was seen within sinusoidal cells (P < 0.05), particularly in zone 1 (P < 0.02). Steatosis was also associated with acinar inflammation (P < 0.005). α-Smooth muscle actin expression was present in association with both lipid peroxidation and fibrosis. Although the effects of steatosis and iron on lipid peroxidation and fibrosis were additive, there was no evidence of a specific synergistic interaction between them. Conclusions: These observations support a model where steatosis exerts an effect on fibrosis through lipid peroxidation, particularly in zone 3 hepatocytes. (C) 2001 Blackwell Science Asia Pty Ltd.

Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein.

Abstract: Background and Aim: The Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) has been reported to be a highly useful marker for hepatocellular carcinoma (HCC) compared with a conventional serum AFP concentration, which allows earlier detection of HCC compared with using other imaging modalities and predicting prognosis after therapy. A collaborative prospective study involving nine Japanese hospitals was conducted to analyze the relationships between the tumor characteristics of a HCC patient and the percentage of AFP-L3/AFP total at the initial detection. Methods: Between 1 October 1996 and 30 September 1997, a total of 388 patients with newly diagnosed HCC were registered. Results: The cut-off level of the percentage of AFP-L3 was altered from 15 to 10%. The AFP-L3-positive HCC patients demonstrated the characteristics of having an advanced tumor, such as the number of tumors, maximum diameter, tumor spread, portal vein invasion, tumor stage, and tumor classification. With the conventional cut-off level of 15% of the percentage of AFP-L3, the malignant characteristics were more definite than that of 10%. However, no significant differences of serum AFP concentration were observed for malignant characteristics such as maximum diameter and histopathological grading. Conclusion: Serum AFP concentration does not reveal a malignancy of HCC, however, the AFP-L3-positive HCC has biologically malignant characteristics, especially portal vein invasion and lower tumor classification, and is an advanced tumor regardless of small tumor size and lower serum AFP concentration. As AFP-L3 shows the tumor characteristics, its presence should be an important factor in the determination of therapy and prognosis of patients.

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis

Abstract: Background and Aims: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. Methods: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. Results: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. Conclusions: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.

Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum.

Abstract: Herbal preparations are widely available and generally regarded by the public as harmless remedies for a variety of medical ailments. We report the first case in Australia of acute hepatitis associated with the Chinese herbal medicine Shou-Wu-Pian, prepared from Polygonum multiflorum. Cholestatic hepatitis developed in a Chinese woman taking this preparation for the greying of her hair, and liver biopsy was consistent with a toxic reaction. Clinical and biochemical resolution occurred following cessation of the drug.

Role of hiatus hernia and gastric mucosal atrophy in the development of reflux esophagitis in the elderly.

Abstract: Background and Aims: The pathogenetic mechanism responsible for the increased prevalence of reflux esophagitis in the elderly remains controversial. The aim of this study was to determine if an increased occurrence of hiatus hernia (HH) and/or a lower rate of gastric mucosal atrophy (GMA) are the main causes of the increased prevalence of reflux esophagitis in elderly patients. Methods: The prevalence of HH, GMA, and reflux esophagitis was investigated by reviewing the endoscopic films of 2788 consecutive patients examined during a 3-year period. Results: The prevalence of esophagitis in males was higher than in females (11.6%vs 7.6%, P < 0.0005). The prevalence of reflux esophagitis and HH was found to increase with age in females, but not in male patients. The prevalence of reflux esophagitis in hernia-positive patients also increased with age in women, but not in men. Age, male gender, presence of HH, and closed-type of GMA were significant risk factors for the prevalence of esophagitis (P = 0.0001, 0.0229, < 0.0001, < 0.0001, respectively). In addition, the risk ratios of HH and low-grade GMA for reflux esophagitis increased with age, and this tendency was higher in female patients than in males. Conclusions: Aging, male gender, HH and closed-type GMA are most likely the risk factors of endoscopically proven reflux esophagitis in Japanese patients.

Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement.

Abstract: Aim: The aim of this study was to examine the effectiveness and toxicity of radiation therapy in combination with transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with extensive portal vein tumor thrombus (PVTT). Methods: The combined therapy was performed in 24 HCC patients with extensive PVTT. External radiation targeted for PVTT (50 Gy in 2 Gy fractions) was performed in combination with repetitive TACE for intralobar lesions using 30–60 mg epirubicin every 3 months, and associations of the following variables with the survival rate were evaluated: gender, age, viral etiology, Child’s class, performance status, extrahepatic metastasis, size and number of HCC, and location of PVTT. Results: The local response confined to PVTT was complete response (CR) in four patients, partial response (PR) in eight patients, no change (NC) in eight patients, and progressive disease (PD) in four patients. By using the stepwise Cox’s regression analysis, only Child’s class was associated with the survival rate. The survival rates after 1 and 2 years were 73 and 21% in Child’s A, 10 and 0% in Child B or C, and 61 and 21% in patients in whom the local response was CR or PR, and 19 and 9% in those in whom the local response was NC or PD, respectively. By using the multiple logistic regression analysis, Child’s class was the only factor associated with the local response (P = 0.006). Conclusions: The combined therapy is feasible and may be useful to reverse PVTT in patients with good hepatic function reserve.

Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease.

Abstract: Background and Aim: Colorectal Paneth cell metaplasia (PCM) is known to be a sign of idiopathic inflammatory bowel disease (IBD), although its distribution and histogenesis are not fully understood. Objectives of this research were to investigate the spatial distribution of PCM in IBD and other forms of colitis (non-IBD), and to find stimuli causing PCM. Methods: We studied multiple biopsy specimens from 181 patients with ulcerative colitis (UC), 159 with Crohn's disease (CD), 448 with non-IBD, and 78 normal controls. Paneth cell metaplasia frequency, at each colorectal site, was evaluated to find possible differences among diseases, phases of activity, and extents of disease. Results: In non-IBD and controls, PCM was rarely (0–1.9%) seen at distal sites, but frequently (up to 48.7%) found at the ascending colon and cecum (P < 0.001). Paneth cell metaplasia frequency was significantly higher in IBD than in non-IBD patients and controls at distal sites (P < 0.001), but did not differ significantly between UC and CD, or among active, resolving, and quiescent phases. In UC, proctitis and left-sided colitis rarely displayed PCM at unaffected sites. Multiple logistic regression analysis revealed that PCM was positively associated with crypt distortion and mononuclear cell infiltration (P < 0.005), but negatively or not significantly associated with crypt atrophy, mucin depletion, acute inflammation, or phase of activity. Conclusions: Paneth cell metaplasia is a non-specific phenomenon in the proximal colon, but distal PCM, which occurs exclusively in affected mucosa, is a useful marker indicating IBD, even in the inactive phase. Regression analysis suggests that repair and regeneration may be the most potent stimuli causing PCM.

Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma.

Abstract: Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. Methods: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n = 1 513 358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. Results: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel– Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B-cell type and 10 (58%) were classified as being in the intermediate grade. Conclusions: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations.

Chronic narcotic use in inflammatory bowel disease patients: Prevalence and clinical characteristics

Abstract: Background: Narcotic addiction can be a significant problem in inflammatory bowel disease (IBD). However, there are few published reports about this problem. Methods: All patients prescribed narcotics chronically in the absence of demonstrable organic pathology were identified on the computerized Brisbane IBD Research Group database (n = 332 patients with informative data as of 1 January 1999). Individual case records were reviewed with regard to clinical, psychiatric and social characteristics of these patients, and the prevalence of psychiatric disorders were compared with a control group of IBD patients. Results: Eleven patients were identified. Nine had complete datasets, eight with Crohn's disease (CD), of which six had previous stricturing ileal disease, and one patient had ulcerative colitis, making a prevalence of 2.7% of IBD patients and 5.1% of CD patients. A 67% prevalence of a psychiatric disorder in narcotic users was significantly greater than the 8% prevalence in the control group of IBD patients (odds ratio 22, 95% CI 3.24-177). Conclusions: A significant proportion of IBD patients without demonstrable organic pathology were chronic narcotic users. Psychiatric disorders are common in this subgroup, as with chronic functional abdominal pain syndromes. It is suggested that inappropriate narcotic use in IBD patients can be reduced by appreciating that narcotics are a temporary therapy only for IBD patients, and awareness of pre-existing social and psychiatric disorders, which not only impact on clinical presentation of pain, but also help define the subgroup of patients who are at risk of narcotic misuse.

Metabolic genotypes and risk for colorectal cancer.

Abstract: Background: Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer. Methods: The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case– control study, and reported as odds ratios (OR) with 95% confidence intervals (CI). Results: None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38–3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99–3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein ɛ4 (OR 0.64; 95% CI 0.31–1.33). Conclusion: No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens.

Use of ursodeoxycholic acid in liver diseases.

Abstract: Ursodeoxycholic acid is currently the only established drug for the treatment of chronic cholestatic liver diseases. It has cytoprotective, anti-apoptotic, membrane stabilizing, anti-oxidative and immunomodulatory effects. Prolonged administration of ursodeoxycholic acid in patients with primary biliary cirrhosis (PBC) is associated with survival benefit and a delaying of liver transplantation. There is evidence that it might even prevent progression of the histologic stage of PBC. It also has a beneficial effect on primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, liver disease associated with cystic fibrosis, chronic graft versus host disease, total parenteral nutrition associated cholestasis and various pediatric cholestatic liver diseases. In the present review the current knowledge about the mechanisms of the action and role of ursodeoxycholic acid in the treatment of various liver diseases has been discussed.

Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations.

Abstract: Background: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. Methods: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. Results: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 ± 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg – ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. Conclusions: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.

Squamous papilloma of the esophagus : Long-term follow up

Abstract: Background and Aim: Squamous papilloma of the esophagus is a rare benign tumor; less than 200 cases have been reported in the literature. The prevalence of endoscopically diagnosed squamous papilloma of the esophagus has been reported in only a very few series, and varies from 0.01 to 0.43%. Clinical relevance and possible association with other pathological conditions, namely if it is a premalignant lesion, remain a matter of debate. The etiology is controversial, although a role of human papilloma virus has been recently proposed. The aim of this study was to try to determine the prevalence, clinical relevance, possible association with other pathological conditions of the upper digestive tract, and possible etiological role of human papilloma virus on our series of squamous esophageal papillomas. Methods: Data from a total of 7618 upper gastrointestinal endoscopies consecutively performed in 4 years were obtained. A 4-year follow up was carried out. Results: Squamous esophageal papilloma was found in nine patients (0.01%). The mean size of polyps was 4 mm and the mean distance from the dental ridge was 25 cm. Only one patient had more than one polyp. Two patients had liver cirrhosis and three had peptic ulcer disease. All squamous esophageal papillomas were removed and tested for human papilloma virus with commercial available kits for in situ hybridization, but none was found positive. Conclusion: Squamous papilloma of the esophagus is an uncommon disease that does not appear to predispose to esophageal cancer. No association was found with human papilloma virus.

Expandable metallic stents should not be used in the treatment of benign esophageal strictures.

Abstract: Expandable metallic stents have become popular in recent years for the treatment of esophageal strictures. While they are undoubtedly of great value in the palliation of malignant strictures and tracheo-esophageal fistulas, there is concern over their use for the treatment of benign diseases. We report three cases, in which such problems were seen following stent insertion for benign esophageal strictures. All three patients developed further strictures above the stents, one was complicated by a tracheo-esophageal fistula and two stents (in one patient) migrated distally into the stomach. Two of the patients underwent subsequent esophageal surgery. In both cases, this proved extremely difficult and hazardous because of the intense fibrotic reaction induced by the stents. Expandable mesh stents should not be used for the treatment of benign esophageal strictures without careful consideration of the potential problems, which can include rendering the problem inoperable.

Intestinal dysfunction in liver cirrhosis: Its role in spontaneous bacterial peritonitis

Abstract: Spontaneous bacterial peritonitis is a common illness in patients with cirrhosis and ascites that occurs without any apparent focus of infection. Bacterial translocation plays an important role in spontaneous bacterial peritonitis and it is evident from a variety of studies that the gut is a major source of this bacteria. Gut motility alterations, along with bacterial overgrowth and changes in intestinal permeability, probably play a role in this bacterial translocation. The present review looks at the role of the intestine in spontaneous bacterial peritonitis induced by liver cirrhosis and the factors influencing bacterial translocation in this disease.

Diagnostic value of serum type IV collagen test in comparison with platelet count for predicting the fibrotic stage in patients with chronic hepatitis C.

Abstract: Background and Aim: The serum type IV collagen test is now used as a diagnostic aid for the detection of liver fibrosis and cirrhosis. Recently, a platelet count has been reported to be a useful marker for assessing the fibrotic stage in chronic hepatitis C. The aim of this study was to compare the usefulness of the serum type IV collagen test and platelet count for diagnosing the fibrotic stage in chronic hepatitis C patients. Methods: The diagnostic values were assessed by the use of receiver operating characteristic (ROC) analysis in 165 patients with chronic hepatitis C, with the exception of those patients with cirrhosis. Results: The serum type IV collagen level increased, and the platelet count decreased significantly with the progression of fibrosis staging. As judged from ROC curves, the serum type IV collagen test was more useful than the platelet count for differentiating moderate or severe fibrosis from no or mild fibrosis. At a cut-off value of 110 ng/mL, the serum type IV collagen test had an overall diagnostic accuracy of 75%, while at a cut-off value of 16 × 104/mm3, the platelet count had a diagnostic accuracy of 70%. The serum type IV collagen test and platelet count were similar in differentiating severe fibrosis from no, mild or moderate fibrosis. Both serum type IV collagen (at a cut-off value of 130 ng/mL) and platelet count (at a cut-off value of 14 × 104/mm3) had a diagnostic accuracy of 73%. Conclusion: The serum type IV collagen test was slightly superior to the platelet count for assessing the fibrotic stage in patients with chronic hepatitis C.

Auditory P300 event-related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a follow-up study.

Abstract: Background and Aims: The P300 event-related potentials (P3ERP) have been recently advocated for detection of cognitive disturbances in early encephalopathy. However, no systematic follow-up study has been conducted to understand the clinical significance of subclinical hepatic encephalopathy (SHE) detected by this or other methods. The present study was therefore undertaken to examine the diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it with that of the number connection test (NCT), and to investigate the clinical outcome of patients with SHE in terms of progression to overt encephalopathy. Methods: P300 event-related potential latencies were measured and the NCT time was recorded in 81 non-encephalopathic cirrhotic patients (Aged 43.8 ± 11 years, 23 alcoholic and 58 non-alcoholics) attending the outpatient department at our tertiary care hospital (All India Institute of Medical Sciences Hospital). Cut-off values for abnormality in the tests were developed from age-, sex- and education-matched controls. Patients were followed up at regular intervals for the development of overt encephalopathy, and the identifiable precipitating factors were noted. The P3ERP latencies (363 ± 34 msec vs 349 ± 23 msec), as well as NCT time (54.6 ± 30.6 s vs 39.5 ± 15.8 s) were significantly prolonged (P < 0.01) in patients with liver cirrhosis when compared with the non-cirrhotic controls. Results: The P3ERP defects were seen in 24.6% of cirrhotic patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of the patients with SHE progressed to overt encephalopathy within a mean duration of 5 months, while only 3.9% of the non-SHE patients did so. Of the patients who developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7% had abnormal NCT. Conclusions: The results of the present study suggest that P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as there is a greater likelihood of overt encephalopathy development in patients with an abnormality detected by these tests than in patients with no such abnormality.

Calcium-parathyroid hormone-vitamin D axis and metabolic bone disease in chronic viral liver disease.

Abstract: Background: The main process involved in hepatic osteodystrophy seems to be osteoporosis, but decreased 25-hydroxylation of vitamin D might lead to osteomalacia and secondary hyperparathyroidism. Methods and Results: We studied bone mineral density (BMD) by using DEXA-Expert Lunar, biochemical markers of bone turnover and calcium-parathyroid hormone (PTH)-vitamin D axis in 100 patients with chronic viral hepatitis secondary to hepatitis C virus: 49 non-cirrhotic (NCir) and 51 with cirrhosis (Cir) confirmed by liver biopsy and/or clinical and biochemical features. When compared to the age-matched population, 25% of the patients had low BMD at the lumbar spine (LS), 26.2% at Ward's triangle, 15.5% at the femoral neck (FN), and 20.2% at the trochanter. No difference was found either between Cir and NCir groups or between sexes. Urinary N-telopeptide was increased in 31.86% of the patients, and negatively correlated with BMD at the LS and trochanter (P < 0.02). Serum bone-specific alkaline phosphatase was elevated in 21% of the patients and negatively correlated with BMD at the trochanter and Ward's triangle (P < 0.02). Fasting 25-hydroxyvitamin D was low in only three Cir patients, with no difference between the Cir and NCir groups, but it was higher in men (51.8 ± 16.0 ng/mL) compared to women (40.4 ± 14.4 ng/mL; P = 0.001). Fasting serum calcium was lower in Cir than NCir patients, P = 0.019. Fasting intact PTH was elevated in 42% of the patients, but the mean serum levels were similar in Cir and NCir groups. Conclusion: We found no evidence of vitamin D deficiency, but cannot exclude the participation of PTH in the high bone turnover and bone loss in the population with chronic viral hepatitis.

Prevalence of endoscopic reflux esophagitis among Koreans

Abstract: Background and Aim: Although reflux esophagitis is believed to be common in the Western population, very few epidemiologic data on reflux esophagitis in Koreans are available. The aims of this study were to evaluate the prevalence of endoscopic reflux esophagitis in patients who came for a physical check-up at Korea University Hospital, and to study the relationship between various factors relevant to reflux disease. Methods: This study was carried out prospectively on 7015 patients who received an esophagogastroduodenoscopy from September 1996 to December 1997. Most of the patients were free of symptoms and had come for their self-paid check-up. Results: The overall prevalence of reflux esophagitis was 3.4%, and most of the patients had a mild degree of esophagitis representing grade 1 in 98.3% and grade 2 in 1.7%. The male : female ratio for esophagitis was 7 : 1, and the body mass index (BMI) was significantly higher in patients with reflux esophagitis. A hiatal hernia was found in 166 patients with esophagitis (68.6%), but only in 9.2% patients without esophagitis (P < 0.05). Smoking and alcohol consumption were associated with the development of reflux esophagitis (P < 0.05). Conclusions: The prevalence of endoscopic reflux esophagitis among Koreans is 3.4%, and most of the patients had a mild grade esophagitis. Smoking, alcohol consumption, the presence of a hiatal hernia and a higher BMI are associated with the development of reflux esophagitis.

Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population.

Abstract: Aim: To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population. Methods: Two thousand five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospectively enrolled in the study. After routine medical examination, including an upper gastrointestinal study and an ultrasonographic examination, all subjects were asked standard questions to check for the presence of any symptoms that suggested dyspepsia. Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA. Results: Of the 2500 persons investigated, 2263 showed no abnormal finding in any medical examination. The presence or absence of symptoms and H. pylori infection was investigated in these 2263 cases. Of these, 201 people (8.9%) experienced nausea, fullness and/or early satiety and were diagnosed as having dysmotility-like dyspepsia, while 118 people (5.2%) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia. The frequency of these symptoms had a tendency to decline with age, although this was not statistically significant. In contrast, the rate of H. pylori infection increased with age. There was no significant relationship between H. pylori infection and any type of functional dyspepsia. Conclusions:Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms.

Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma.

Abstract: Aim: The aim of this study is to assess the poly ADP-ribosylation activity in human hepatocellular carcinoma (HCC) and in liver cirrhosis (LC) as compared to the activity in normal livers (NL). Methods: Hepatocellular carcinoma and LC tissues were sampled from 19 patients with HCC. Normal liver tissue was obtained from 19 patients with metastatic liver cancer. Poly ADP-ribosylation activity of these tissues was measured by using [32P]-adenylate nicotinamide adenine dinucleotide (NAD)-incorporation into the 116-kDa protein. Nicotinamide adenine dinucleotide glycohydrolase activity of these tissues was determined with thin layer chromatography. The immunohistochemical expression of Ki-67 was also assessed as a parameter of cell proliferative activity. Results: The poly ADP-ribosylation of the 116 kDa protein was significantly increased in patients with HCC and LC as compared with NL (P < 0.0001, P < 0.05, respectively) and was inhibited by poly (ADP-ribose) polymerase inhibitors in a dose-dependent manner. There was no significant difference in NAD glycohydrolase activity among the three groups. A significant correlation was found between the Ki-67 positive cell rate and the relative radioactivity of poly ADP-ribosylation in HCC patients (r = 0.794, P < 0.0001). The poly ADP-ribosylation of the 116 kDa protein of LC was significantly higher in patients who had recurrences of HCC after hepatic resection than in patients without recurrence (P < 0.05). Conclusion: Poly ADP-ribosylation of the 116 kDa protein in HCC patients might be enhanced with its proliferative activity, and poly ADP-ribosylation of the same protein in LC patients might be a useful parameter of carcinogenic potential for predicting HCC recurrence after hepatectomy in patients who have had HCC.