bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of multiple mutations in the core promoter and pre‐core/core region of hepatitis B virus genome on the response to interferon in e antigen‐positive chronic hepatitis B
Authors: Zhang Xinxin , Han Yongnian , Lu Zhimeng , Gao Jian , Luo Zhenghui , Zhang Donghua
Published: March 2003

Background and Aims: Hepatitis B virus (HBV) genomic mutations may be one of the factors that influence the efficacy of interferon (IFN) therapy. The aim of this study was to investigate the effects of mutations in different parts of the HBV genome on IFN therapy.

Methods: We studied the baseline clinical, biochemical, serologic and virologic parameters in 17 patients with e antigen‐positive chronic hepatitis B. The DNA sequence of the X gene and pre‐core/core gene in serum samples of these patients was analyzed before the initiation of IFN therapy.

Results: All five patients with the T1762–A1764 mutation were IFN responsive, while among the 12 remaining patients, only two responded to therapy. Among five patients with both a pre‐core A1896 mutation and a mutation in the epitope aa 107–118 of the core region, four were non‐responders whereas the fifth responded to therapy. In three other patients with A1896 mutations, one with simultaneous mutations in five lymphocytic epitopes did not respond to therapy; the two remaining patients with concomitant mutations in one or two epitopes were responsive. Serum HBV‐DNA levels were lower and titers of antibody to hepatitis B virus core antigen‐immunoglobin M (anti‐HBc‐IgM) were higher in the responders than in the non‐responders. Hepatitis B virus genotypes B and C were found to be in all these Chinese patients.

Conclusions: These results suggest that HBV genomic mutations, serum viral loads and titers of anti‐HBc‐IgM might be predictive of the efficacy of IFN therapy. These clinical findings should be further investigated by in vivo and in vitro experiments.
Iron overload impairs pro‐inflammatory cytokine responses by Kupffer cells
Authors: Olynyk John K , Clarke Sharon L
Published: March 2003

Aim: The aim of the present study was to determine the effect of chronic iron overload on Kupffer cell cytokine production.

Methods: Kupffer cells were isolated from rats that were fed either a control or iron‐supplemented diet for 12 months. Cytokine mRNA and protein levels were determined by using a ribonuclease protection assay and ELISA, respectively.

Results: Baseline levels of tumor necrosis factor‐α, transforming growth factor‐β1, interleukin‐6 and granulocyte macrophage colony stimulating factor were similar in iron‐loaded and control Kupffer cells. Following the addition of lipopolysaccharide to control cells, tumor necrosis factor‐alpha, interleukin‐1α and interleukin‐6 mRNA levels increased. Tumor necrosis factor‐alpha mRNA and protein levels were reduced by 40 and 60%, respectively, in iron‐loaded cells compared with controls following the addition of lipopolysaccharide. Interleukin‐6 mRNA levels in iron‐loaded Kupffer cells were also reduced. Granulocyte macrophage colony stimulating factor mRNA levels remained unchanged in controls, but were significantly elevated in iron‐loaded cells. Tumor growth factor‐β1 mRNA and protein levels were similar in control and iron‐loaded cells.

Conclusion: Deposition of iron in Kupffer cells in chronic dietary iron overload results in an impaired pro‐inflammatory cytokine response to lipopolysaccharide. Our observations may have relevance to the altered immune function observed in chronic iron‐overload syndromes.
Modulation of doxorubicin sensitivity by cyclosporine A in hepatocellular carcinoma cells and their doxorubicin‐resistant sublines
Authors: Shiraga Kunihiro , Sakaguchi Kohsaku , Senoh Tomonori , Ohta Takeyuki , Ogawa Shin , Sawayama Tomoyuki , Mouri Hirokazu , Fujiwara Akiko , Tsuji Takao
Published: March 2003

Background and Aims: Cyclosporine A (Cys) and verapamil (Ver) sensitize multidrug‐resistant (MDR) cells to various anticancer drugs by interacting with membrane glycoproteins involved in the drug efflux. In the present study, we assessed the effect of Cys on the modulation of doxorubicin (DOR) sensitivity in hepatocellular carcinoma (HCC) cell lines, and their DOR‐resistant sublines.

Methods: The sensitivity to DOR and the chemosensitizing effects of Cys were assessed by using two human HCC cell lines, PLC/PRF/5 and Hep‐3B, and their DOR‐resistant sublines, PLC/DOR and 3B/DOR. The expression of multidrug resistance 1 (MDR1) and multidrug resistance‐associated protein (MRP) mRNA in these cells were detected by using a RT‐PCR. The HCC cell lines grown in individual wells of 24‐well plates were incubated with DOR that were sequentially diluted in culture medium in combination with 5 μmol/L Cys for 24 h. The cell viability in each well was measured by using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay.

Results: The mRNA of MDR1 and that of MRP were readily detectable in the HCC cell lines by RT‐PCR. When 5 μmol/L Cys was added to the culture, the 50% inhibiting concentration (IC50) of DOR was reduced from 0.93 ± 0.29 μg/mL to 0.32 ± 0.10 μg/mL in PLC/PRF/5, and from 0.25 ± 0.07 μg/mL to 0.09 ± 0.04 μg/mL in Hep‐3B. Furthermore, in the presence of 5 μmol/L Cys, the IC50 of DOR was reduced from 48.63 ± 17.04 μg/mL to 0.49 ± 0.14 μg/mL in PLC/DOR, and from 4.60 ± 1.22 μg/mL to 0.15 ± 0.06 μg/mL in 3B/DOR. The amounts of PCR products of MDR1 mRNA in PLC/DOR and 3B/DOR were greater than those in PLC/PRF/5 and Hep‐3B, respectively.

Conclusions: In HCC, the amplification of MDR1 mRNA is probably the main mechanism underlying acquired DOR resistance. Cyclosporine is also indicated to be highly active in potentiating the anticancer activity of DOR in HCC cells and their DOR‐resistant sublines.
Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis
Authors: Das Ananya , Dhiman Radha K , Saraswat Vivek A , Verma Meera , Naik Subhash R
Published: March 2003

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.
Comparison of truncal hair distribution in alcoholic liver disease and alcohol‐related chronic pancreatitis
Authors: Kumar Nirmal , Aggarwal Shri Ram , Anand Bhupinder S
Published: March 2003

Abstract The present study shows that scanty hair distribution over the trunk is a specific finding in patients with alcoholic liver disease (ALD), and is not seen in alcoholic pancreatitis. This observation not only provides a useful clinical marker of individuals at increased risk of developing alcohol‐related liver disease, but from the pathogenetic viewpoint, it suggests that at the tissue level, the male sex hormones protect the liver against ethanol‐related damage.
High risk of Helicobacter pylori infection in young Japanese dentists
Authors: Honda Kimio , Ohkusa Toshifumi , Takashimizu Ichizen , Watanabe Mamoru , Amagasa Mitsuo
Published: March 2003

Background and Aim: The route of person‐to‐person transmission of Helicobacter pylori may be either fecal–oral or oral–oral, because the bacterium is found in both dental plaque and feces. We assessed the prevalence of H. pylori seropositivity, which reflects present or past infection, in Japanese dentists exposed occupationally to dental plaque.

Methods: We examined the sera of 60 dentists (34 who were 20–29 years or older, and 26 who were over 30 years of age) and 60 age‐matched controls by using quantitative ELISA for antibodies of the immunoglobulin G class to H. pylori.

Results: The proportion of dentists seropositive for H. pylori (42 of 60, 70%) was higher than in controls (23 of 60, 38%). The odds ratio for H. pylori seropositivity (3.8; 95% CI, 1.76–8.02) was high in the dentists. When dentists were classified in terms of the length of their practice, the odds ratio for seropositivity (10.4; 95% CI, 3.26–32.85) was high in the dentists practising for fewer than 4 years. The proportion of dentists in their 20s who were seropositive was greater than that in the group of age‐matched controls.

Conclusion: Japanese young dentists are at a high risk for H. pylori infection, with the oral–oral transmission route being possibly the most common.
Significance of serum soluble Fas antigen level in chronic hepatitis C patients treated with interferon: Relationship to the therapeutic response
Authors: Ohkawa Kazuyoshi , Hiramatsu Naoki , Mochizuki Kiyoshi , Mita Eiji , Iio Sadaharu , Yoshihara Harumasa , Kato Michio , Masuzawa Manabu , Kasahara Akinori , Sasaki Yutaka , Hori Masatsugu , Hayashi Norio
Published: March 2003

Background and Aim: Fas system‐mediated cytotoxicity is thought to be involved in the development of liver injury in hepatitis C virus (HCV) infection. In this study, we investigated serum soluble Fas antigen levels in chronic hepatitis C patients treated with interferon and their correlation with the therapeutic response.

Methods: The subjects were 67 chronic hepatitis C patients who underwent a 24‐week course of α‐interferon therapy. Patients were categorized into three groups; sustained responders (n = 22), transient responders (n = 24), and non‐responders (n = 21), according to changes in the serum alanine aminotransferase level during and after therapy. The viral genotype, viremic level and diversity in the hypervariable region were examined before therapy. Serum soluble Fas antigen levels were assayed by using serum samples taken at the beginning and the end of therapy.

Results: In the univariate analysis, serum soluble Fas antigen levels tended to be higher in non‐responders (10.0 ± 3.4 ng/mL) than in sustained responders (8.5 ± 3.0 ng/mL) and transient responders (8.2 ± 2.1 ng/mL; P = 0.13 and P < 0.05). The non‐response to therapy was observed in eight of the 15 (53%) patients with serum soluble Fas antigen ≥ 11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only significant factor contributing to the sustained response was a low HCV viremic level (P = 0.0046). Significant factors contributing to the non‐response were a high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas antigen level (P = 0.0483).

Conclusions: High production levels of soluble Fas antigen may be associated with a poor response to interferon therapy in chronic hepatitis C patients.
Clinician opinion on the management of patients with hepatic colorectal metastases
Authors: Moore Katrina , Bokey Les , Chapuis Pierre , Tait Noel
Published: March 2003

Background and Aims: Clinical practice is determined by many different factors, but with the advent of evidence‐based medicine, there may be a tendency to concentrate upon the scientific facts when decision‐making rather than focusing on the patient. Furthermore, individual clinician opinion or bias may potentially influence patient management. This study outlines clinician opinion with regard to management of patients with hepatic colorectal metastases, and compares it to present practice in the Sydney metropolitan area.

Methods: Clinician opinion was assessed by using a questionnaire and compared to results from a prospective multicenter study looking at patterns of care of patients with hepatic colorectal metastases.

Results: Clinicians participating in the present study had a good knowledge of the current evidence concerning hepatic colorectal metastases and its treatment. However, there was a discrepancy between clinician knowledge that matched scientific evidence and actual clinical practice.

Conclusions: This study suggests that clinician bias/opinion does influence patterns of care for patients with hepatic colorectal metastases.
Alteration of DNA methylation in gastrointestinal carcinogenesis
Authors: Fang Jing Yuan , Xiao Shu Dong
Published: March 2003

Abstract DNA methylation is the main epigenetic modification in humans. The methylation of promoter inhibits the transcription in most genes. In normal tissues, isolated CpG dinucleotides in bulk chromatin are often methylated, whereas cytosines in CpG islands are unmethylated. In neoplasms including gastrointestinal cancer, this pattern of methylation is commonly reversed. The alteration of DNA methylation plays a key role in the process of carcinogenesis. The gastrointestinal carcinogenesis is suggested to be associated with the decrease of total genomic DNA methylation; hypomethylation of certain specific oncogenes such as c‐myc, c‐Ha‐ras, c‐fos and α‐fetoprotein; and hypermethylation of the promoter of some tumor suppressor genes containing p16INK4A, E‐cadherin and hMLH1 genes. This review focuses on the analysis methods for methylation, studies for aberrant DNA methylation in gastrointestinal carcinogenesis, and the intervention changing methylation, including the treatment of 5‐azacytidine, supplement of folate and gene therapy.
An evaluation of the PyloriTek test for the diagnosis of Helicobacter pylori infection in Chinese patients before and after eradication therapy
Authors: Wong Wai Man , Wong Benjamin Chun Yu , Tang Vera Shun Yim , Lai Kam Chuen , Yuen Siu Tsan , Leung Suet Yi , Hu Wayne Hc , Lam Shiu Kum
Published: March 2003

Background and Aim: The PyloriTek Test Kit (a 1‐h rapid urease test) was developed for the rapid diagnosis of Helicobacter pylori (H. pylori) during endoscopy. Most studies were performed in Western populations. The aim of this study was to evaluate the PyloriTek test for the diagnosis of H. pylori infection in Chinese population.

Methods: Eligible patients without prior treatment or who had had recent eradication of H. pylori were recruited. During endoscopy, biopsies were taken from the antrum and corpus for an in‐house rapid urease test (RUT), histology and for the PyloriTek test (one antral and one corpus biopsy). Results of the PyloriTek test were compared with the gold standard (RUT and histology).

Results: Analysis of PyloriTek test results from the antrum alone (101 patients before eradication and 52 patients after eradication) showed a sensitivity, specificity, and accuracy of 96.3, 97.9, and 97.0%, respectively, for cases before eradication, and an accuracy of 100% for cases after eradication. The benefit of an additional body biopsy was marginal and only occurred in the pre‐eradication group.

Conclusion: The PyloriTek test was highly accurate for the diagnosis of H. pylori infection before and after eradication therapy, with a final result available at 1 h, which is unmatched by any invasive test so far. It enhances clinical decision‐making by allowing the clinicians or endoscopists to start therapy on the same day of an endoscopy visit. One biopsy from the antrum is highly reliable for this purpose.
Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non‐alcoholic cirrhosis and extrahepatic portal venous obstruction
Authors: Satapathy Sanjay K , Narayan Sajith , Varma Neelam , Dhiman Radija K , Varma Subhash , Chawla Yogesh
Published: March 2003

Background and Aims: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non‐alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO.

Methods: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell–Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell–Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age‐matched controls.

Results: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 ± 1.36%vs control 1.22 ± 0.17%, P < 0.05), but not so with NAC (2.01 ± 0.69%) and EHPVO (mean 0.99 ± 0.1%vs control 0.66 ± 0.1%, P > 0.05). Howell–Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 ± 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 ± 1.3%, P < 0.05).

Conclusion: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.
Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus1
Authors: Dhiman Radha K , Arke Leishangthem , Bhansali Anil , Gupta Sanjay , Chawla Yogesh K
Published: March 2003

Background and Aims: Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM).

Methods: Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real‐time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects.

Results: Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean ± SEM) was higher (9.3 ± 1.0 vs 4.6 ± 0.6; P = 0.002), and ejection fraction was lower (57.4 ± 4.0 vs 74.2 ± 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 ± 2.4 vs 20.0 ± 1.4; P = 0.034 and 9.3 ± 1.0 vs 5.9 ± 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 ± 4.0 vs 72.6 ± 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 ± 5.4 vs 80.4 ± 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 ± 6.1 vs 65.4 ± 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying.

Conclusion: Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.
Autoimmune hepatitis in the Indian subcontinent: 7 years experience
Authors: Gupta Rajesh , Agarwal Shri Ram , Jain Monika , Malhotra Veena , Sarin Shiv Kumar
Published: March 2003

Background: Autoimmune hepatitis (AIH) is presumed to be rare in India. The present prospective study was carried out to determine the prevalence, clinical, biochemical and histological profile of patients with AIH in India.

Methods: Consecutive patients with chronic liver disease suspected to be AIH, were screened for antinuclear antibodies (ANA), antismooth muscle antibodies (ASMA), antimitochondrial antibody (AMA), and anti‐liver kidney microsomal antibodies (anti‐LKM‐1). Serum protein electrophoresis and liver biopsy were done. Autoimmune hepatitis was diagnosed according to the International Autoimmune Hepatitis Group criteria.

Results: Fifty of 1358 (3.43%) patients with chronic liver disease were diagnosed as autoimmune liver disease; 39 with AIH, two with overlap syndrome, five with primary sclerosing cholangitis, and four with primary biliary cirrhosis. Twenty‐nine patients were categorized as definite AIH and 10 as probable AIH. Autoimmune hepatitis was common in females (males : females 1:3), with a mean age of 31 ± 17 years. Patients often presented with fatigue, jaundice and anorexia. Skin lesions (58%), joint symptoms (30%), and menstrual abnormalities (26%) were not uncommon. Mildly elevated alkaline phosphatase and hyper gamma globulinemia were seen in 78 and 91% patients, respectively. Eighty percent of patients were type I AIH, while 20% of cases remained unclassified. Histopathological changes included piecemeal necrosis (100%), plasma cell infiltration (91%), rosette formation (82%), and cirrhosis (76%). Overall mortality was 25% during a mean follow up of 15.7 ± 17.0 months.

Conclusions: Our results clearly demonstrate that: (i) AIH is not uncommon in India; and (ii) while the profile and spectrum of AIH resembles that seen in the West, Indian patients present late, often in a cirrhotic state.
Effect of omeprazole‐induced achlorhydria on trefoil peptide expression in the rat stomach
Authors: Kang Baolin , Alderman Barbara M , Nicoll Amanda J , Cook Greg A , Giraud Andrew S
Published: March 2003

Background:

Omeprazole is an inhibitor of the H+K+ ATPase of the gastric parietal cell, which is used clinically to suppress gastric acid secretion. It has also been found to inhibit gastric mucin production; however, its effects on the synthesis and secretion of the trefoil peptides, which are also expressed by mucus cells, and which play a key role in cytoprotection and epithelial repair, are unknown.

Methods:

Rats (n = 8) were given either omeprazole (30 mg/kg per day; p.o.) or inert carrier for 1 week, and the effects on synthesis and peptide expression of the gastric trefoil peptides, TFF1/pS2 and TFF2/SP, were compared.

Results:

As expected, omeprazole treatment abolished H+ ion production with a mean gastric juice pH of 7.2 compared with 2.4 for controls. The omeprazole group had elevated total protein levels of 35‐fold and TFF1/pS2 peptide levels elevated fourfold, respectively, but not TFF2/SP peptide in gastric juice, suggesting that the increased pH reduced the viscosity of adherent mucus, thereby increasing gastric juice concentrations by dissolution of adherent TFF1/pS2 and increased secretion. Concomitant with increased TFF1/pS2 secretion was a fall in predominantly antral mucosal trefoil peptide concentrations. In contrast to trefoil secretory rates, the steady‐state synthesis of both TFF1/pS2 and TFF2/SP was unchanged after omeprazole treatment, implying both a large cellular pool of processed peptide and rapid secretion.

Conclusion:

The increase in the concentration of TFF1/pS2 in gastric secretions during chronic omeprazole‐induced achlorhydria may be important in preventing tissue injury and promoting repair in response to an increased luminal bacterial population.
Glucose‐6‐phosphate dehydrogenase deficiency is associated with increased initial clinical severity of acute viral hepatitis A
Authors: Gotsman Israel , Muszkat Mordechai
Published: March 2003

Background and Aim:

In glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, the enzyme is deficient in liver cells as well as in erythrocytes. It has been suggested that this may be associated with a more severe clinical presentation of acute viral hepatitis A. The aim of this study is to determine the severity of liver disease in patients with viral hepatitis and G6PD deficiency.

Methods:

Eighteen patients with diagnosed G6PD deficiency and acute hepatitis A were compared with 18 matched control patients with hepatitis A in a university hospital for liver disease severity and clinical outcome.

Results:

Two of 18 patients with G6PD deficiency had neurological deterioration. Patients with G6PD deficiency had a mean peak prothrombin time (PT) that was significantly prolonged as compared with the control group (15.5 ± 3.7 vs 12.9 ± 2.0 s, respectively, P < 0.02), and a significantly higher proportion had an abnormal PT (PT > 13.3 s): 61 versus 11% (P < 0.0001). Hemolysis occurred in 44% of the G6PD deficiency patients. Total and direct bilirubin were significantly higher in all patients with G6PD deficiency, including patients without hemolysis. There was no significant difference in liver enzyme levels between the two groups. Patients with G6PD deficiency had a longer average hospital stay (9.5 ± 4.8 vs 3.4 ± 0.8 days, respectively, P < 0.001). There was no difference in the final clinical outcome between the two groups, and recovery of liver function was seen in all patients.

Conclusions:

Glucose‐6‐phosphate dehydrogenase deficiency in patients with hepatitis A causes a more severe initial clinical presentation, but does not alter the final clinical outcome.
Effect of alcohol withdrawal on liver transaminase levels and markers of liver fibrosis
Authors: Campbell Stewart , Timms Peter M , Maxwell Paul R , Doherty Elizabeth M , Rahman Mohammad Z , Lean Michael EJ , Danesh Booth J
Published: March 2003

Background and Aim:

Acute alcohol withdrawal causes changes in hepatic blood flow and metabolism that may result in liver damage. This study aims to assess liver function tests and markers of hepatic fibrogenesis following alcohol withdrawal in alcoholics with clinically compensated liver disease.

Methods:

Serial liver function tests and clinical assessments were performed on 22 male alcoholics during alcohol withdrawal. Plasma tissue inhibitor of metalloproteinase 1 (TIMP1), an inhibitor of collagen degradation, and plasma amino‐terminal procollagen III peptide (PIIINP), a collagen precursor molecule, were measured in these alcoholics and in 11 control subjects.

Results:

Transaminase levels did not change significantly over 7 days when all subjects were analyzed together. However, 32% of subjects showed a marked transaminase rise. These subjects did not differ from the others in baseline characteristics or short‐term outcome, but had a greater benzodiazepine requirement. Only one subject consumed paracetamol (acetaminophen; 1–2 g/day). He had the largest transaminase rise. By comparing PIIINP assays, intact PIIINP concentration appears to increase following alcohol withdrawal. The TIMP1 levels were elevated in alcoholic subjects, but did not change following withdrawal.

Conclusions:

Increasing PIIINP suggests that hepatic fibrogenesis increases, or hepatic clearance falls, during acute alcohol withdrawal. The TIMP1 elevation in these alcoholics suggests that the inhibition of collagen degradation occurs while liver disease is still compensated. The period following alcohol withdrawal may be a time of marked increased susceptibility to paracetamol. The biochemical changes we observed were not associated with adverse short‐term outcome, but the cumulative effect after repeated episodes of abrupt withdrawal may be of concern.
Vitamin C inhibits corpus gastritis in Helicobacter pylori‐infected patients during acid‐suppressive therapy
Authors: Yoshinaga Masahiro , Ohtani Akira , Harada Naohiko , Fukuda Yuriko , Nawata Hajime
Published: March 2003

Background:

Previous studies have shown that gastric acid suppression worsens corpus gastritis in Helicobacter pylori (H. pylori)‐positive patients. We evaluated the effect of acid‐suppressive therapy and vitamin C on H. pylori‐associated gastritis.

Methods:

Forty patients with reflux esophagitis were divided into three groups by the status of H. pylori and therapy: group A (n = 15), H. pylori (+) and omeprazole 20 mg; group B (n = 15), H. pylori (+) and omeprazole 20 mg + vitamin C 1200 mg; and group C (n = 10), H. pylori (−) and omeprazole 20 mg. In all three groups, the mucosal interleukin (IL)‐8 contents, H. pylori colonization density, neutrophil infiltration in the corpus, and serum gastrin were evaluated at entry and 2 weeks after starting therapy; in group B, serum vitamin C levels were also measured.

Results:

In group A, the IL‐8 contents and the degree of neutrophil infiltration during therapy exceeded those at entry, whereas in groups B and C, these values did not change significantly with treatment. Helicobacter pylori colonization density during therapy was similar to that at entry in all three groups. The serum gastrin (in all groups) and vitamin C levels (in group B) during therapy exceeded those at entry.

Conclusions:

Potent acid suppression worsens H. pylori‐associated corpus gastritis, although such worsening gastritis may be inhibited by vitamin C.
Chemoprevention of hepatocellular carcinoma: Concept, progress and perspectives
Authors: Okuno Masataka , Kojima Soichi , Moriwaki Hisataka
Published: March 2003

Abstract Hepatocellular carcinoma (HCC) often develops in patients with chronic liver diseases associated with hepatitis B (HBV) and hepatitis C (HCV) virus infections with high incidences. Particularly, post‐therapeutic recurrence encountered after the curative treatment of the preceding HCC may limit the prognosis. Thus, prevention of HCC is of great significance. In the present review, immunopreventions with α‐interferon and glycyrrhizin, as well as chemoprevention with acyclic retinoid, are discussed. α‐Interferon prevents the development of HCC not only in patients with a long‐term elimination of HCV (sustained virological responders), but in ones with normalized serum aminotransferases (sustained biochemical responders). Glycyrrhizin also suppresses serum aminotransferases and thereby prevents the tumor development, even though the compound does not have antiviral activity for HBV or HCV by itself. Therefore, suppression of hepatic necroinflammation by these drugs may serve to prevent hepatocarcinogenesis. In contrast, acyclic retinoid suppresses the post‐therapeutic recurrence in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induces the disappearance of serum lectin‐reactive α‐fetoprotein (AFP‐L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of apoptosis induction by the retinoid via tissue transglutaminase is implicated. In future, a combination of immunopreventive and chemopreventive therapies may give a clue to the further advances of cancer prevention, and thereby to the improvement of the prognosis of cirrhotic patients.
Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease
Authors: BARIOL CAROLYN , MEAGHER ALAN P , VICKERS CHRISTOPHER R , BYRNES DAVID J , EDWARDS PAUL D , HING MICHAEL , WETTSTEIN ANTONY R , FIELD ANDREW
Published: March 2003

Background and Aim Thalidomide is clinically effective in the treatment of graft versus host disease in bone marrow transplantation and aphthous ulceration in HIV infection. It appears to exert a selective effect on tumor necrosis factor‐α (TNF‐α) production. Tumor necrosis factor‐α is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy and safety of thalidomide in symptomatic IBD.

Methods Eleven patients (nine males, mean age 33 years, range 20–77 years) with chronic inflammatory bowel disease (six Crohn’s disease (CD), four ulcerative colitis (UC), one indeterminate colitis (IC)) who were symptomatic despite standard medical therapy were administered a daily dose of thalidomide for 12 weeks in an open‐labeled protocol. Their response was assessed by using clinical, colonoscopic, histological, and immunological methods.

Results Two patients withdrew at 3 weeks because of mood disturbances. Of the remaining nine patients, eight (five CD, two UC and one IC) had a marked clinical response, while one patient with CD had no response. The mean stool frequency decreased from 4.3 to 2.3 per day (P = 0.0012), and the stool consistency increased from 2.1 to 1.2 (P = 0.02). The mean Crohn’s Disease Activity Index decreased from 117 to 48 (P = 0.0008). Endoscopic inflammatory and histological grade, C‐reactive protein and erythrocyte sedimentation rate (ESR) all decreased significantly (P = 0.011, P = 0.03, P = 0.023 and P = 0.044, respectively). However, the serum TNF‐α levels did not change. Side‐effects included mild sedation, xerostomia and skin dryness in all, constipation in three, and minor abnormalities in nerve conduction in one patient.

Conclusion These data strongly suggest that thalidomide is an effective short‐term treatment for symptomatic IBD.
Non‐cirrhotic portal fibrosis (idiopathic portal hypertension): Experience with 151 patients and a review of the literature
Authors: DHIMAN RADHA KRISHAN , CHAWLA YOGESH , VASISHTA RAKESH KUMAR , KAKKAR NANDITA , DILAWARI JANG BAHADUR , TREHAN MANJIT SINGH , PURI PANKAJ , MITRA SOMEN KUMAR , SURI SUDHA
Published: March 2003

Background: Non‐cirrhotic portal fibrosis (NCPF), the equivalent of idiopathic portal hypertension in Japan and hepatoportal sclerosis in the United States of America, is a common cause of portal hypertension in India. The clinical features, portographic and histological findings, and management of 151 patients with non‐cirrhotic portal fibrosis are presented.

Methods: The disease is diagnosed by the presence of unequivocal evidence of portal hypertension in the definite absence of liver cirrhosis and extrahepatic portal vein obstruction (EHPVO). Retrospective analysis of records of 151 patients with NCPF was analyzed for the clinical presentation, physical findings, laboratory tests, radiological and histological findings, and for the outcome of treatment.

Results: The disease is characterized by massive splenomegaly with anemia, preserved liver function and benign prognosis in a majority of patients. Splenoportovenography (SPV) showed massive dilatation of the portal and splenic veins, and the presence of collaterals. Twenty‐four (15.9%) patients showed evidence of natural/spontaneous shunts (splenorenal 15, umbilical nine) on SPV; these patients had a lower incidence of variceal bleeding. Liver histology demonstrated maintained lobular architecture, portal fibrosis of variable degree, sclerosis and obliteration of small‐sized portal vein radicles, and subcapsular scarring with the collapse of the underlying parenchyma. Piecemeal or hepatocytic necrosis was absent in all histology specimens. Three patients showed nodular transformation along with abnormal liver functions, and may represent late manifestation of NCPF where features are similar to those seen in patients with incomplete septal cirrhosis. In the initial part of the study, surgery (side‐to‐side lieno‐renal shunt) was the preferred modality of treatment, however, endoscopic sclerotherapy or variceal ligation has now become the preferred first line of management of variceal bleeding.

Conclusions: The epidemiological and clinical features of NCPF have more similarity to IPH than has previously been documented. The development of spontaneous shunts tends to protect these patients from variceal bleeding.
Four cases of hepatitis B virus‐related fibrosing cholestatic hepatitis treated with lamivudine
Authors: JUNG SAERA , LEE HAN CHU , HAN JI‐MIN , LEE YUN‐JUNG , CHUNG YOUNG‐HWA , LEE YUNG SANG , KWON YOUNGMEE , YU EUNSIL , SUH DONG JIN
Published: March 2003

Fibrosing cholestatic hepatitis (FCH) is a rare and extremely severe form of hepatitis B virus (HBV) infection. This condition was originally described in HBV‐infected recipients after a liver transplantation. Recently, FCH has been reported not only in liver transplant recipients, but also in other immunosuppressed patients. It is characterized clinically by cholestatic hepatic dysfunction, and pathologically by severe periportal fibrosis, cholestasis, widespread balloon degeneration of hepatocytes, and only a mild infiltration of inflammatory cells. Without treatment, FCH is universally fatal within a few months of diagnosis. There have been only two isolated case reports of FCH with long‐term patient survival, and one case report with treatment failure after lamivudine therapy. Because of the rarity of this clinical entity, the therapeutic efficacy of lamivudine in patients with FCH cannot be evaluated systematically. Here, we present four patients with HBV‐related FCH treated with lamivudine. One received antineoplastic therapy for acute lymphoblastic leukemia, and the other three were renal graft recipients. Two patients who developed FCH after a renal transplantation survived with an improvement in liver function and were followed up for 20 and 30 months, respectively, and were found to be in good health. However, the other two patients died of sepsis, possibly as a consequence of the immunosuppression with hepatic failure despite lamivudine treatment. Our experience suggests that lamivudine can alter the grave natural history of FCH.

© 2001 Blackwell Science Asia Pty Ltd
Wild‐type and ‘a’ epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody
Authors: MESENAS STEVEN J , CHOW WAN C , ZHAO YI , LIM GEK K , OON CHONG J , NG HAN S
Published: March 2003

Aims This study aims to examine the genomic variants of the ‘a’ epitope in chronic hepatitis B virus (HBV) carriers positive for both hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti‐HBs).

Methods Eighteen HBV carriers were studied. Hepatitis B virus (HBV) DNA was extracted and the ‘a’ epitope region was amplified and sequenced.

Results Eighteen Chinese asymptomatic HBV carriers were studied. There were 13 patients who were positive for both HBsAg and anti‐HBs. Of these, one patient had only wild‐type HBV, three had a viral mixture, and five had only ‘a’ epitope variant HBV. Of the three patients with a viral mixture, all had variants in the less conserved region (123–137). Of the five patients with pure HBsAg mutants, three had variants in the less conserved region while two had variants in the highly conserved region. In this study with a limited number of patients, the serum alanine aminotransferase (ALT) levels were higher in patients with wild‐type HBV, compared with those with either ‘a’ epitope variants or a viral mixture consisting of wild type and variants.

Conclusion Eight of the nine (89%) patients positive for both HBsAg and anti‐HBs harbored an ‘a’ epitope variant. The lower ALT levels seen in patients who had either pure ‘a’ epitope variant or a mixture of wild type and mutants suggest that a closer monitoring of these ‘a’ epitope variants should be required, as patients carrying these infectious viral strains may remain asymptomatic.
Evolution of colorectal cancer: Change of pace and change of direction
Authors: JASS JEREMY R , YOUNG JOANNE , LEGGETT BARBARA A
Published: March 2003

Abstract This review compiles evidence for an alternative to the classical adenoma–carcinoma
sequence in the evolution of colorectal cancer. It is suggested that between 30 and
50% of colorectal cancers are not initiated by mutation of the tumor suppressor
gene APC, but through the epigenetic silencing of genes implicated in the
control of differentiation, cell cycle control and DNA repair proficiency. The precursor
polyps are often characterized by a serrated architecture, and include hyperplastic
polyps, admixed polyps and serrated adenomas. The alternative pathway is heterogeneous
and may culminate in cancers showing low or high level DNA microsatellite instability
(MSI‐L and MSI‐H, respectively), and in cancers that are microsatellite stable (MSS).
Cancers showing DNA MSI may be characterized by an accelerated evolution. Cancers
in hereditary non‐polyposis colorectal cancer show features of both classical (adenoma
and APC mutation) and alternative pathways (rapid evolution, MSI‐H and lack of chromosomal instability).
Autoantibody in a patient with chronic hepatitis C virus infection showing complete remission after interferon therapy
Authors: AKASHI YOSHIHIRO , INOH MASAYUKI , SETO KUNIO , GAMO NAOYUKI , KUBOKI MAKOTO , KURATA NORIYUKI
Published: March 2003

Abstract A 42‐year‐old woman was admitted to Kinashi Ohbayashi Hospital for liver dysfunction. She presented with hepatitis C viral infection accompanied by autoimmune hepatitis‐like serological manifestations, such as antinuclear antibody (ANA), antismooth muscle cell antibody and especially anti‐ribonucleoprotein (RNP) antibody and anti‐SSB antibody. After interferon therapy, hepatitis C virus was not detected and ANA, anti‐RNP antibody and anti‐SSB antibody disappeared. To our knowledge, this is the first reported hepatitis C patient showing anti‐RNP antibody and anti‐SSB antibody, having complete remission after interferon therapy.
Systemic administration of liposome‐encapsulated OK‐432 prolongs the survival of rats with hepatocellular carcinoma through the induction of IFN‐γ‐producing hepatic lymphocytes
Authors: UEHARA KAZUHIRO , ICHIDA TAKAFUMI , SUGAHARA SATOSHI , ISHIKAWA TORU , YAMAGIWA SATOSHI , YOSHIDA YUHEI , NOMOTO MINORU , KATOH MASASHI , SATOH HIROSHI , WATANABE HISAMI , ABO TORU , ASAKURA HITOSHI
Published: March 2003

Background: OK‐432 is known to increase the host antitumor response. We previously reported that systemic administration of OK‐432 (OK‐Lipo) specifically induced hepatic lymphocytes in mice. Here we aimed to investigate the antitumor effect of OK‐Lipo on hepatocellular carcinomas (HCC) in experimental rats.

Methods: Diethylnitrosamine was administered for 12 weeks to all rats (n = 36). Rats were divided into three groups of 12 rats each. One group was injected with OK‐Lipo from week 5 (OK‐5w group) and another from week 9 (OK‐9w group). A control group was injected with saline from week 5 (Non‐OK group). At week 13, five rats from each group were used for histological analysis and immunofluorescence assays (surface phenotypic and intracellular cytokine analysis of the mononuclear cells in the liver, spleen and peripheral blood). The remaining rats were observed for the remainder of their survival period.

Results: The mean survival times of Non‐OK, OK‐5w, and OK‐9w groups differed significantly (98.0 ± 5.3 days, 116.0 ± 5.8 days, and 106.0 ± 5.4 days, respectively,

P < 0.01). Histological examination revealed many apoptotic tumor cells, infiltration of lymphocytes and macrophages in the OK‐5w group. The two‐color immunofluorescence assay showed that the proportion of natural killer (NK) cells and IFN‐γ‐producing cells in the liver were significantly higher in the OK‐5w group.

Conclusions: These findings showed that systemic administration of OK‐Lipo contributed to prolonging the survival of rats with HCC. OK‐Lipo induced NK cells and IFN‐γ‐producing cells specifically in the liver and these cells seemed to reduce hepatocarcinogenesis and tumor growth.
Predictive factors by multivariate analysis for colorectal cancer in Malaysian patients undergoing colonoscopy
Authors: TAN YAN M , ROSMAWATI MOHAMED , RANJEEV PRABHAKERAN , GOH KHEAN L
Published: March 2003

Background: The majority of colorectal cancers are still diagnosed in patients who present with symptoms especially in countries where colorectal screening programs are not practised. The aim of our study was to determine the predictive factors for colorectal cancer in patients referred for colonoscopy.

Methods: A prospective study of 485 consecutive patients who underwent colonoscopy during a 22‐month period was performed. All patients answered a detailed questionnaire. Indications for colonoscopy and the findings were recorded.

Results: The mean age of the study population was 55.7 ± 14.7 years. There were 221 (45.6%) males and 264 (54.4%) females. Sixty‐five (13.4%) were Malays, 298 (61.4%) were Chinese and 112 (23.1%) were Indians. Multiple backward stepwise regression analysis revealed that independent predictors for colorectal cancer (odds ratio [95% CI]) were the presence of rectal bleeding (4.3 [4.0–8.0]) and iron deficiency anemia (4.0 [3.6–10.2]). In those aged 50 and over, male gender (4.5 [2.2–9.3]) and abdominal pain (3.1 [1.4–6.7]) were also significant positive predictors of cancer.

Conclusions: With the ever‐increasing demand for gastrointestinal endoscopy, the appropriate utilization of colonoscopy is essential to afford prompt patient evaluation. Our study supports the need to prioritize the use of colonoscopy in patients with rectal bleeding and iron deficiency anemia. In the older patient where the background prevalence of colorectal cancer is higher, referral for colonoscopy is also justified.

© 2002 Blackwell Science Asia Pty Ltd
Does a fatty meal improve hepatic clearance in patients after endoscopic sphincterotomy?
Authors: LAI KWOK‐HUNG , PENG NAN‐JING , LO GIN‐HO , LIN CHIUN‐KU , CHAN HOI‐HUNG , HSU PING‐I , CHENG JIN‐SHIUNG , WANG YA‐YU
Published: March 2003

Background: Delayed biliary emptying is a cause of recurrent bile duct stones in patients after endoscopic sphincterotomy (ES) for choledocholithiasis. This study aimed to evaluate the effect of fatty meal on hepatic clearance in patients after ES.

Methods: Sixty patients who had received ES and complete clearance of bile duct stones were enrolled. Delayed hepatic clearance (45 min clearance of radioisotope [E45′] < 57%) from quantitative cholescintigraphy (QC) and absence of sphincteric function confirmed by sphincter of Oddi manometry were found in each patient after normalization of liver function. Patients then received another QC 30 min after a fatty meal (two fried eggs and 250 mL full milk, fat 28 g) within 2 months.

Results: Improvement of hepatic clearance in QC after fatty meal was found in 20 of 24 (83%)
cholecystectomized patients and 27 of 36 (75%) patients with intact gallbladder.
The E45′ after fatty meal was significantly higher than that without fatty
meal (56 ± 12%vs 40 ± 9% in cholecystectomized
patients, P < 0.001; 52 ± 16%vs 35 ± 11%
in patients with intact gallbladder, P < 0.001). All patients tolerated the fatty meal well during fatty meal QC.

Conclusions: Fatty meal can improve hepatic clearance in both patients with intact gallbladder and after cholecystectomy, so routine restriction of fat after ES may be inappropriate. However, further studies are needed to evaluate the role of diet in the prevention of recurrent biliary complications.

© 2002 Blackwell Science Asia Pty Ltd