bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management issues in chronic viral hepatitis: Hepatitis C
Authors: Sievert William 
Published: March 2003

Abstract  The natural history of chronic hepatitis C virus (HCV) infection and intervention with antiviral therapy are closely linked issues that cause the greatest controversy and concern for the person infected with HCV, as well as for the clinician involved in the assessment and treatment of people with chronic HCV infection. The outstanding challenge of natural history is to identify the person who is likely to develop serious liver disease, and to make that determination early in the course of chronic HCV infection when treatment is likely to be of the greatest benefit. Significant advances in the therapy of chronic HCV infection have occurred over the past decade. A sustained virological response (SVR), defined as undetectable HCV‐RNA in blood 6 months after completing antiviral treatment, is the best indicator of a beneficial treatment effect. Relapse, breakthrough or non‐response should all be regarded as unsuccessful outcomes of therapy. Interferons are still the mainstay of antiviral therapy for chronic HCV infection. The combination of interferon and ribavirin has improved SVR by decreasing the relapse rate. Treatment responses vary according to host factors such as age and gender, fibrotic severity and to viral factors like genotype and viral load. Patients with genotype 1 HCV and a high viral load require 12 months of treatment to achieve a SVR in approximately 30%, compared to those with genotypes 2 or 3 who achieve a SVR in approximately 65% after 6 months. Patients who relapse after an end‐of‐treatment response to interferon monotherapy have a good chance of responding to combination interferon and ribavirin given for 6 months, but a longer treatment course should be considered in less optimal cases. At present, the treatment of those with non‐response is less clear, but there is interest in more intense forms of interferon therapy, such as induction dosing or pegylated interferon in combination with ribavirin. Clinicians need to be aware of the common side‐effects of interferon and ribavirin so that appropriate counseling and testing can be instituted before and during therapy. The combination of pegylated interferon and ribavirin will be the new standard of therapy for hepatitis C and pegylated interferon monotherapy provides quite acceptable efficacy for those patients intolerant of ribavirin. Current data strongly support the concept that SVR in HCV infection (or treatment‐induced latency) provides a cure in terms of its beneficial effects on quality of life and sustained amelioration of liver injury.© 2002 Blackwell Publishing Asia Pty Ltd
Is severe liver disease a common outcome for people with chronic hepatitisC?
Authors: Dore Gregory J , Freeman Anthony J , Law Matthew , Kaldor JohnM 
Published: March 2003

Abstract  For people with chronic hepatitis C, an assessment of their riskof progression to advanced liver disease is a major priority. Earlystudies of the natural history of chronic hepatitis C suggestedthat development of cirrhosis was a relatively common outcome, evenin the first 20 years of infection. These studies wereeither cross‐sectional liver clinic series of people referred forassessment to specialist clinics, or longitudinal cohorts of peoplewith post‐transfusion hepatitis. More recent studies (particularlylong­itudinal community‐based cohorts) indicate that liverdisease progression is generally slow, and that a minority of peoplewith chronic hepatitis C will develop advanced liver disease. Basedon an extensive review of studies reporting on chronic hepatitisC natural history, we have developed a Markov model of liver diseaseprogression. This model estimates that the risk of progression tocirrhosis is 7% and 20% after 20 and 40 yearsof infection, respectively. Corresponding estimates for hepatitisC‐related mortality are 1% and 4%. However, liverdisease progression is highly variable, and certain subgroups ofpeople with chronic hepatitis C are at increased risk of advancedliver disease. Those groups include people with a heavy alcoholintake, those who have coinfection with HIV or HBV, and those whohave already progressed to moderate to severe hepatic fibrosis.© 2002 Blackwell Publishing Asia Pty Ltd
Hepatic Kupffer cell phagocytotic function in rats with erythrocytic‐stage malaria
Authors: NOBES MICHAEL S , GHABRIAL HANY , SIMMS KATRINA M , SMALLWOOD RICHARD A , MORGAN DENIS J , SEWELL RICHARD B 
Published: March 2003

Abstract
Background:
In the erythrocytic phase of malaria, Kupffer cells show marked hypertrophy and hyperplasia and are filled with malarial pigment. However, phagocytic function in this state has not been well characterized. The aim of the present study was to use mouse Plasmodium berghei to infect rats with malaria and study the phagocytic function and morphology of Kupffer cells.
Methods:
We used a recirculating isolated perfused rat liver (IPRL) to quantitate Kupffer cell phagocytic clearance of radiolabeled albumin–latex over 120 min in high parasitemia (53 ± 6%; n = 7) and low parasitemia (∼1%; n = 4) malaria‐infected rats and littermate controls (n = 7 and n = 4, respectively). In a further group of high‐parasitemic rats, perfusion was ceased after 7 min and liver radioactivity also measured. Electron microscopy was performed after perfusions.
Results:
In high‐parasitemia malaria rats, clearance of radiolabeled latex from IPRL perfusate over 120 min was significantly (P < 0.01) faster than in controls, with a lower area under the curve (0.19 ± 0.02 vs 0.43 ± 0.07 /mL per min, respectively) and shorter half‐life (t1/2k; 2.4 ± 0.6 vs 10.0 ± 2.3 min, respectively). Low‐parasitemia rats were identical to controls. After 7 min perfusion in high‐parasitemic rats (n = 4), total radioactivity in liver homogenates was higher than in controls (n = 4; 33.1 ± 6.2 vs 18.4 ± 1.9% of injected radiolabel; P < 0.05). Electron microscopy showed latex in Kupffer cells, more abundantly seen in high‐parasitemic animals.
Conclusions:
Total Kupffer cell phagocytic activity of the liver is markedly increased in rats with a high parasitemic load of malarial P. berghei infection. This is presumed to reflect an upregulation of scavenger activity phagocytosing erythrocytes and their breakdown products.© 2002 Blackwell Publishing Asia Pty Ltd
An early cancer of the gastric cardia arising from carditis after long‐term gastroesophageal reflux disease in the absence of Helicobacter pylori infection
Authors: Yagi Kazuyoshi , Nakamura Atsuo , Sekine Atsuo , Oyamatsu Manabu , Tamiya Yoichi , Watanabe Hedenobu 
Published: March 2003

Abstract  We describe an early gastric cardiac cancer in a patient who had suffered long‐term gastroesophageal reflux disease (GERD) but showed no evidence of infection with Helicobacter pylori. Proximal gastrectomy and partial resection of the lower esophagus was performed. Histological examination revealed the lesion to be a gastric cardiac adenocarcinoma, which had partially invaded the submucosal layer. Intestinal metaplasia was also found in some areas. Inflammation, however, appeared to be limited to the gastric cardia. This cancer may have arisen via a sequence of carditis and cardiac intestinal metaplasia, due primarily to the GERD and not to H. pylori infection.© 2002 Blackwell Publishing Asia Pty Ltd
Issues of malnutrition and bone disease in patients with cirrhosis
Authors: Donaghy Anthony 
Published: March 2003

Abstract  Malnutrition is a frequent complication of cirrhosis, and many studies have demonstrated the adverse influence of malnutrition on clinical outcomes in patients with cirrhosis. The coexisting complications of fluid overload and ascites may mask the severity of malnutrition, particularly in the early stages of its development. During periods of decompensation, protein and energy requirements are higher, and many patients have inadequate nutritional intake at these times. Further, protein supplementation should not be restricted ad hoc in cirrhotic patients, as for the vast majority of patients dietary protein does not precipitate hepatic encephalopathy. The impairment of hepatic glycogen storage in cirrhotic patients effects a state of accelerated starvation with catabolism of fat and protein to provide substrates for gluconeogenesis. Recent studies have demonstrated the efficacy of nocturnal nutritional supplements in improving nitrogen balance. Resistance to the actions of the anabolic growth factors insulin and growth hormone (GH) is common in cirrhosis, and recent studies have shown that GH resistance, in particular, may be overcome with exogenous GH therapy. Hypermetabolism may be observed in up to one‐third of cirrhotic patients. The recent exciting observation that beta‐blocker therapy can decrease energy expenditure and catecholamine levels in these patients indicates the need for further intervention studies of beta‐blockers as metabolic therapy in cirrhosis.© 2002 Blackwell Publishing Asia Pty Ltd
What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?
Authors: Lee Cheng‐Chi , Wu Chun‐Ying , Chen And Gran‐Hum 
Published: March 2003

AbstractBackground: Hepatolithiasis is a well‐known etiology of cholangiocarcinoma. However, whether or not hepatolithiasis influences the presentation of cholangiocarcinoma is not very clear. To help clarify this, we conducted the present study to investigate the clinicopathological characteristics of cholangiocarcinoma with hepatolithiasis. As well, we made a comparison between the presence and absence of hepatolithiasis in patients with cholangiocarcinoma to determine the impact of hepatolithiasis.Methods: Among 140 patients with histologically proven cholangiocarcinoma at the Taichung Veteran General Hospital between October 1982 and December 2000, 38 were found to have concomitant hepatolithiasis. Patients were evaluated on the basis of age, gender, presenting symptom, laboratory data, preoperative liver function (indocyanine green test), tumor markers, histological differentiation, lymph node involvement, and organ metastasis. Data were statistically analyzed using the chi‐squared test and Student's t‐test. Analysis of survival was performed using the Kaplan–Meier method, and univariate analysis and multivariate analyses for survival were performed by Cox proportional hazard model.Results: The cholangiocarcinoma with hepatolithiasis group (CC + HL) was found to be predominantly female, with more common presentation of fever and less presentation of jaundice (P < 0.05). In addition, patients with cholangiocarcinoma without hepatolithiasis (CC − HL group) had higher serum bilirubin levels and more advanced histological differentiation (P < 0.05). As well, the percentage of resectability of the CC + HL group was higher than that of the CC − HL group, although it was not statistically significant. Univariate and multivariate analyses for overall survival showed that those patients with an age older than 65 years, hypoalbuminemia, poor histological differentiation, and a presence of hepatolithiasis were prone to a graver prognosis, albeit none of them were statistically significant. Resectability was the only independent predictor of a favorable prognosis with significant difference.Conclusions: The clinicopathological features of cholangiocarcinoma with concomitant hepatolithiasis showed few differences from that without hepatolithiasis. Resectability was the only predictor that favored a good prognosis.© 2002 Blackwell Publishing Asia Pty Ltd
Clinical characteristics and natural history of patients with low‐grade reflux esophagitis
Authors: Manabe Noriaki , Yoshihara Masaharu , Sasaki Atsunori , Tanaka Shinji , Haruma Ken , Chayama Kazuaki 
Published: March 2003

AbstractBackground and Aim: Although the incidence of reflux esophagitis (RE) has recently increased in Japan, the majority of these cases are mild (Los Angeles classification grades A and B). In order to consider therapy for these patients, it is important to understand the natural history of mild RE. There is little information concerning the natural course of RE, particularly low‐grade disease. The goal of this study is to elucidate the natural course of patients with mild RE and to identify specific prognostic indicators associated with a poor outcome.Methods: One hundred and five patients with mild RE were followed, without medical treatment, by endoscopy in addition to a questionnaire regarding symptomatology, for a mean of 5.5 years (range, 2.0–8.8 years) after initial diagnosis. Factors associated with the development of severe esophagitis were analyzed.Results: Endoscopically, 11 patients (10.5%) progressed to more severe forms of RE (recurrent progressive (RP) group), 60.0% of patients relapsed without disease progression (recurrent non‐progression group), and the remaining 29.5% of patients had no further episodes of RE (isolated episode group). Risk factors for progressive disease were increased age, female sex, the presence of symptoms at initial diagnosis by endoscopy, presence of a hiatal hernia, absence of atrophic gastritis, and absence of Helicobacter pylori infection. Despite having all risk factors, there were six patients who did not progress to more severe forms of RE. The primary esophageal peristaltic amplitude in these patients was significantly higher than in the RP group.Conclusions: Among patients with mild RE, only 10.5% progressed to more severe forms of RE. The patients with risk factors are candidates for aggressive therapy in order to prevent the progression of the RE disease process.© 2002 Blackwell Publishing Asia Pty Ltd
Detection of Chlamydia pneumoniae by polymerase chain reaction–enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls
Authors: Chen Wangxue , Li Dong , Wilson Ian , Chadwick Vinton S 
Published: March 2003

Abstract
Background and Aim
:

It has been suggested that Chlamydia is an organism that may have the potential to cause inflammatory bowel disease (IBD) in susceptible individuals. Chlamydia pneumoniae has emerged as an important human pathogen in the last decade. The objective of the present study was to investigate the frequency of the presence of C. pneumoniae DNA in intestinal biopsies from patients with IBD and from non‐IBD controls.
Methods
:

The DNA was extracted from 222 colonoscopic biopsies, which were obtained from 11 patients with Crohn's disease (CD), 18 patients with ulcerative colitis (UC) and from 37 non‐IBD control patients. The presence of the C. pneumoniae omp1 gene and C. trachomatis 16S rRNA gene was determined using a rapid and sensitive polymerase chain reaction‐enzyme immunoassay (PCR‐EIA).
Results
:

The C. pneumoniae‐specific DNA was detected in 32 (14.4%) of 222 endoscopic biopsies. Among them, C. pneumoniae DNA were found in nine of 42 (21.4%) biopsies from patients with CD, nine of 59 (15.3%) biopsies from patients with UC, and 14 out of 122 (11.4%) biopsies from non‐IBD control patients, respectively. Moreover, the percentage of patients with at least one biopsy positive for C. pneumoniae was higher, although not statistically significant, in CD (36.4%) and UC patients (38.9%) compared to non‐IBD controls (16.2%). In contrast, C. trachomatis DNA was detected in only two of 222 (0.9%) biopsy samples.
Conclusion
:
The C. pneumoniae DNA was detected in the intestine of both patients with IBD and in non‐IBD control patients, probably reflecting the high prevalence of this organism in the environment. The moderate yield of positive biopsies in our IBD patients and the fact that the detection rate of C. pneumoniae DNA was similar in endoscopic biopsies from IBD patients and non‐IBD controls does not support a direct role for this organism in the pathogenesis of IBD.© 2002 Blackwell Publishing Asia Pty Ltd
Inhibitory effects of the new anti‐inflammatory agent, IS‐741, on spontaneous colitis in HLA‐B27/β2‐microglobulin transgenic rats
Authors: Makino Jin , Andoh Akira , Hata Kazunori , Yotsuya Shuichi , Shikama Hiroshi , Imamura Masashi , Fujiyama Yoshihide , Bamba Tadao 
Published: March 2003

Abstract Background: A novel anti‐inflammatory drug, IS‐741, blocked the adhesion of inflammatory cells to microvascular endothelial cells both in vivo and in vitro. Transgenic rats expressing human leukocyte antigen (HLA)‐B27 and human β2‐microglobulin (HLA‐B27 rats) spontaneously develop chronic colitis, which resembles human inflammatory bowel disease. In the present study, the authors examined the efficacy of IS‐741 against spontaneous colitis in HLA‐B27 rats.Methods: The HLA‐B 27 rats were divided in two groups after the development of colitis. IS‐741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days.Results: The HLA‐B27 rats treated with IS‐741 remained healthy; the wet weight of the colon was significantly lower in the IS‐741‐treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and the submucosa in the control HLA‐B27 rats, but these changes were attenuated in the IS‐741‐treated group. The mucosal damage score was also significantly reduced by treatment with IS‐741. IS‐741 significantly reduced the mucosal myeloperoxidase activity and mucosal cytokine‐induced neutrophil chemoattractant‐1 levels. IS‐741 also reduced CD3‐positive T‐cell infiltration.Conclusion: IS‐741 suppressed the spontaneous colitis that developed in HLA‐B27 rats. Some of the actions of IS‐741 may be associated with its inhibitory effects on the adhesion of neutrophils to endothelial cells. The findings from the present study suggest that IS‐741 may be a useful new therapeutic agent for inflammatory bowel disease.
Three‐dimensional examination of hepatic stellate cells in rat liver and response to endothelin‐1 using confocal laser scanning microscopy
Authors: Oikawa Hiroki , Masuda Tomoyuki , Kawaguchi Junzo , Sato Ryo 
Published: March 2003

Abstract Background and Aim: Hepatic stellate cells (HSC) are located in the space of Disse and are considered to participate in the regulation of sinusoidal flow. The contractility of quiescent HSC in normal liver has remained controversial, unlike activated HSC in injured liver. The aim of the present study was to examine the morphological changes in quiescent HSC in response to endothelin‐1 (ET‐1) perfusion.Methods: Sections (50 µm thick) obtained from 15 normal rat livers with or without ET‐1 perfusion (1 or 400 nmol/L) were stained immunohistochemically with antiglial fibrillary acidic protein (GFAP) antibody and then examined using confocal laser scanning microscopy. For examination of HSC, hepatic lobules were divided into three anatomic regions from the portal areas to the central veins. The length of HSC cytoplasmic processes and area of the sinusoids relative to the section area, excluding portal tracts and central veins, were measured.Results: The GFAP‐positive HSC were distributed relatively evenly in the hepatic lobules and those in region 2 (the area between periportal and pericentral areas) tended to have longer cytoplasmic processes. Perfusion of 1 or 400 nmol/L ET‐1 for 25 min resulted in swelling of the cell bodies of GFAP‐positive HSC and condensation of the intermediate filaments compared with those perfused with buffer only. Although narrowing of the sinusoidal lumen was observed in each region after perfusion with 400 nmol/L ET‐1, there was no apparent shortening of the cytoplasmic processes of HSC. These findings were also confirmed quantitatively.Conclusion: In the normal rat liver, quiescent HSC are not involved in the regulation of sinusoidal blood flow in response to ET‐1.
Downregulation of the proteasome subunits, transporter, and antigen presentation in hepatocellular carcinoma, and their restoration by interferon‐γ
Authors: Matsui Masanori , Machida Sanae , Itani‐Yohda Teru , Akatsuka Toshitaka 
Published: March 2003

Abstract
Background
: In our previous study, expressions of human histocompatibility leukocyte antigens class I molecules (HLA‐I) and the transporter associated with antigen processing (TAP) 1/2 genes were investigated in seven hepatocellular carcinoma (HCC) cell lines. Two cell lines, Hep‐3B and HuH‐7, showed a reduced level of TAP, which might cause the low surface expression of HLA‐I. In order to understand the downregulation mechanism of antigen presentation in tumors, the two cell lines were further investigated.
Methods
: Expressions of HLA‐I and antigen presentation‐related genes were analyzed by flow cytometry and polymerase chain reaction, respectively. Antigen presentation was tested in 51Cr‐release assays.
Results
: Flow cytometric analyses revealed low surface expression of HLA‐I on Hep‐3B and HuH‐7 cells. Introduction of HLA‐A2 gene did not result in a high surface expression of HLA‐A2. This suggested the downregulation of HLA‐I expression might be related to defects in the antigen presentation machinery. We then examined expression levels of various antigen presentation‐related genes. Hep‐3B and HuH‐7 demonstrated low expression of the low‐molecular‐weight protein (LMP) 2, LMP7, TAP1, and HLA‐I heavy‐chain transcripts. The downregulation of these genes was dissolved by treatment with γ‐interferon. Furthermore, allo‐specific cytotoxic T lymphocyte (CTL) lines failed to recognize Hep‐3B and HuH‐7 cells, while they killed IFN‐γ‐treated Hep‐3B and HuH‐7 cells.
Conclusions
: Our results suggest that defects in the antigen presentation‐related molecules might cause downregulation of HLA‐I expression, antigen presentation, and subsequently, escape from specific CTL killing. The downregulation could be restored by IFN‐γ treatment, suggesting the potential use of IFN‐γ for therapeutic purposes.
Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning†
Authors: Shinoda Masahiro , Shimazu Motohide , Wakabayashi Go , Tanabe Minoru , Hoshino Ken , Kitajima Masaki 
Published: March 2003

Abstract
Background:
Brief periods of hepatic ischemia produce immediate tolerance for subsequent prolonged ischemia. Although the beneficial effect of this ischemic preconditioning is recognized, the mechanism itself remains poorly understood.
Methods:
Male Wistar rats were divided into two groups: a control group that was subjected to 30 min of ischemia + following reperfusion, and an ischemic preconditioning group that was subjected to 5 min of ischemia + 5 min of reperfusion + 30 min of ischemia + following reperfusion. By using this model, hepatic damage, microcirculatory disturbances, and tumor necrosis factor‐α protein production and mRNA expression were analyzed during the course of reperfusion in both groups. For the hepatic damage evaluations, hepatic enzyme levels, histology, apoptosis analysis, and intravital microfluorography for dead cells were examined. For the microcirculatory disturbance analysis, an adhesion molecule and intravital microfluorography for endothelial‐adherent leukocytes were examined.
Results:
In the ischemic preconditioning group, ischemia/reperfusion injuries (shown by hepatic enzymes elevation, histological degeneration, and increases in the number of apoptotic cells and microfluorographic dead cells) were markedly reduced. Moreover, microcirculatory disturbances represented by intercellular adhesion molecule‐1 expression and leukocyte adhesion on the endothelium were ameliorated. Tumor necrosis factor‐α protein production and mRNA expression were also suppressed in the ischemic preconditioning group.
Conclusion:
The suppression of tumor necrosis factor‐α and the subsequent amelioration of microcirculatory disturbances were observed, suggesting that the mechanism underlying the protective effect of ischemic preconditioning in hepatic ischemia/reperfusion injuries may involve tumor necrosis factor‐α and microcirculatory regulation.© 2002 Blackwell Publishing Asia Pty Ltd