Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestatic hepatitis and diffuse liver fibrosis have been described in immunosuppressed patients with hepatitis B virus or hepatitis C virus infection as fibrosing cholestatic hepatitis (FCH). FCH is characterized by cholestasis, with only a modest increase in aminotransferase levels. The pathologic picture typically shows periportal and perisinusoidal fibrosis, scarce mixed infiltrates, hepatocellular ballooning, and histologic cholestasis. We report two patients with diffuse fibrosis and cholestasis quite similar to the histologic picture of FCH, but in whom neither hepatitis B virus nor hepatitis C virus infection could be shown, highlighting the potential contribution of cytomegalovirus infection and azathioprine toxicity in the development of this severe complication of solid-organ transplantation.
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PMID:Fibrosing cholestatic hepatitis-like syndrome in hepatitis B virus-negative and hepatitis C virus-negative renal transplant recipients. 1153 98

We identified two cases of chronic active hepatitis with liver fibrosis induced by lipid lowering drugs of the statin and fibrate classes despite regular monitoring of transaminases. There are few reports of clinically significant hepatitis induced by these drugs and even fewer cases of fibrosis. Given the growing use of these drugs, there are implications for monitoring patients on long-term therapy for liver damage.
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PMID:Liver fibrosis attributed to lipid lowering medications: two cases. 1155 21

The pathogenesis of hepatitis C virus (HCV)-associated liver injury involves many genes from multiple pathogenic pathways. cDNA array analysis, which examines the expression of many genes simultaneously, was used to achieve new insights into HCV liver injury. Membrane-based cDNA arrays of 874 genes compared HCV-associated cirrhosis with autoimmune hepatitis-associated cirrhosis as an inflammatory and cirrhotic control, and with nondiseased liver tissue. Array analysis identified many differentially expressed genes that are important in inflammation, fibrosis, proliferation, signaling, apoptosis, and oxidative stress. Genes up-regulated in HCV-associated cirrhosis were predominantly associated with a Th1 immune response, fibrosis, cellular proliferation, and apoptosis. Novel observations of differential gene expression included increased expression of secreted apoptosis-related protein 3, a Wnt pathway gene possibly involved in cellular apoptosis. EMMPRIN (CD147) and discoidin domain receptor 1 (CD167) were also shown to be increased and are likely to play a role in liver fibrosis. Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of 15 genes. The comparison of HCV cirrhosis with autoimmune hepatitis cirrhosis showed a marked difference in the apoptosis-associated gene profile with HCV cirrhosis characterized by increased proapoptotic gene expression whereas autoimmune hepatitis was characterized by increased expression of both antiapoptotic and proapoptotic genes. Furthermore, expression of beta-catenin and the fibrosis-associated protein EMMPRIN were localized by immunohistochemistry to the plasma membranes of hepatocytes and biliary epithelium. In conclusion, HCV-associated cirrhosis was characterized by a proinflammatory, profibrotic, and proapoptotic gene expression profile.
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PMID:Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression. 1183 85

Thirty-eight cases clinically diagnosed as advanced schistosomiaisis were subject to splenectomy in Dongzhi County Special Hospital for Schistosomiasis because of portal hypertension, splenomegaly and/or hypersplenism. Liver biopsy was undertaken in all cases during surgical intervention. Before operation, ultrasonography on the liver and spleen was carried out. Also done was biochemical assay on several indices related to liver damage and fibrosis. Among the 38 cases, 24 were diagnosed as schistosomiasis by the finding of eggs in feces, 13 were diagnosed by positive serological test with IHA or COPT, and only in one case, the diagnosis of schistosomiasis was doubtful before operation. However, the eggs were found in the liver section upon histological examination. All the 38 cases had symptoms and signs of portal hypertension and most of them had general symptoms. Histories of hematemesis and melena were recorded in three cases. The causes of hospitalization were mainly splenomegaly and abdominal distension, and two were suffering from upper gastrointestinal bleeding. Upon histopathological examination, schistosome eggs were found in 33 out of 38 cases. Advanced schistosomaiasis was shown in 18 cases and schistosomiasis associated with hepatitis or cirrhosis was seen in other 20 patients. The main pathological changes were egg granulomas with different degrees of fibrosis and some differences in the pathological changes between schistosomal liver fibrosis (SLF) and mixed liver cirrhosis (both schistosome and hepatitis in origin) were seen. Compared with normal ultrasonography, in all the 38 cases, the length of the left and right liver, and the spleen, and the thickness of the left liver, the width of portal trunk, were all out of normal ranges. The differences between the patients and normal records were significant. However, there were no statistically significant differences in terms of above-mentioned indices as well as liver parenchyma changes on ultrasound between advanced schistosomaiasis and schistosomiasis complicated with hepatitis or cirrhosis (all P>0.5). According to WHO classification criteria on ultrasonography for schistosomiasis, among 20 cases combined with hepatitis or cirrhosis, 11 cases fell in Grade II, and nine cases in Grade III hepatic fibrosis, whereas among 18 cases with schistosomiasis fibrosis, 12 and six were in Grade II and III, respectively. The mean value of serum MAO, PIIIP, IVC and HA in the 38 cases were all significantly higher than normal range. However, no significant differences (all P>0.1) were seen between advanced schistosomiasis and those complicated with hepatitis or cirrhosis in terms of the levels of the four indices. The results showed that ultrasonography has its importance in the diagnosis and evaluation of liver fibrosis. However, in differentiation of the two types of liver damage, ultrasound does not provide important information. Histopathological examination, on the other hand, can provide useful information to identify the hepatic diseases.
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PMID:Study on histopathology, ultrasonography and some special serum enzymes and collagens for 38 advanced patients of schistosomiasis japonica. 1202 Aug 97

Cyclooxgenase (COX) and phospholipase A(2) (PLA(2)) are crucial rate-limiting enzymes involved in the conversion of arachidonic acid to prostaglandin H(2), the precursor of various compounds including prostaglandins (PGs), prostacyclin, and thromboxanes in the process of PGs' synthesis. Recent studies have shown increased levels of COX(2) in adjacent cirrhotic tissue of hepatocellular carcinoma. The relationship between the expression of COX(2) or cytosolicPLA(2) (cPLA(2)) and liver fibrosis has not been described previously. We used 45 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsies from patients with chronic hepatitis, consisting of 7 cases of F(0), 10 cases of F(1), 10 cases of F(2), 9 cases of F(3) and 9 cases of liver cirrhosis (LC) according to the New Inuyama Classification of the staging of liver fibrosis. The expression of COX(2) and cPLA(2) was investigated by immunohistochemistry, western blotting and image analysis. The positive signals for COX(2) and cPLA(2) were observed in the cytoplasm of hepatocytes. The signal intensity of COX(2) increased significantly with the progression of liver fibrosis (P<0.001) and no significant difference was observed in the relative amount of cPLA(2) from group F(0) to group LC. According to the New Inuyama Classification of hepatitis activity grading, 45 samples were classified as group A(1) (23 cases), group A(2) (19 cases) and group A(3) (3 cases). No significant differences were found in the relative amount of COX(2) and cPLA(2) between group A(1) and group A(2-3). Significant correlation was observed between the relative amount of COX(2) and hyaluronan (P<0.01). Our findings suggested that COX(2) may be involved in liver fibrogenesis.
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PMID:Expression of cyclooxygenase 2 and cytosolic phospholipase A(2) in the liver tissue of patients with chronic hepatitis and liver cirrhosis. 1207 14

Although several mouse models of AIH have been described, no model is ideal. Indeed, the disease is self-limited in each model, and none is associated with significant liver fibrosis or progression to cirrhosis. Nevertheless, these models should be useful for testing different hypotheses regarding the initiation of AIH. Still, each model poses unique limitations. The EAIH model initiated by immunization with crude liver antigens in CFA has been plagued by a high prevalence of hepatitis lesions in CFA controls and inconsistencies in results. The TGF beta-1 and IL-2 deficient models lead to high in utero mortality and short median life spans in the surviving animals. Lastly, all models require more detailed characterization of the antigen specificity of infiltrating liver T cells and the pathogenesis of liver cell injury.
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PMID:Animal models of autoimmunity. 1236 80

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, p.o., 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, p.o., 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.
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PMID:The anti-fibrogenic effect of a pharmaceutical composition of [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (oltipraz) and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB). 1243 1

Liver fibrosis represents a major medical problem with significant morbidity and mortality. Worldwide hepatitis viral infections represent the major cause liver fibrosis; however, within the United States chronic ethanol consumption is the leading cause of hepatic fibrosis. Other known stimuli for liver fibrosis include helminthic infection, iron or copper overload and biliary obstruction. Fibrosis can be classified as a wound healing response to a variety of chronic stimuli that is characterized by an excessive deposition of extracellular matrix proteins of which type I collagen predominates. This excess deposition of extracellular matrix proteins disrupts the normal architecture of the liver resulting in pathophysiological damage to the organ. If left untreated fibrosis can progress to liver cirrhosis ultimately leading to organ failure and death if left untreated. This review will discuss the molecular events leading to liver fibrosis. The discussion will include collagen gene regulation and proliferative signals that contribute to the amplification of the hepatic stellate cell, the primary fibrogenic cell type that resides in the liver.
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PMID:Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell. 1245 23

RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. However, its potential to treat or prevent disease remains unproven. Fas-mediated apoptosis is implicated in a broad spectrum of liver diseases, where inhibiting hepatocyte death is life-saving. We investigated the in vivo silencing effect of small interfering RNA (siRNA) duplexes targeting the gene Fas (also known as Tnfrsf6), encoding the Fas receptor, to protect mice from liver failure and fibrosis in two models of autoimmune hepatitis. Intravenous injection of Fas siRNA specifically reduced Fas mRNA levels and expression of Fas protein in mouse hepatocytes, and the effects persisted without diminution for 10 days. Hepatocytes isolated from mice treated with Fas siRNA were resistant to apoptosis when exposed to Fas-specific antibody or co-cultured with concanavalin A (ConA)-stimulated hepatic mononuclear cells. Treatment with Fas siRNA 2 days before ConA challenge abrogated hepatocyte necrosis and inflammatory infiltration and markedly reduced serum concentrations of transaminases. Administering Fas siRNA beginning one week after initiating weekly ConA injections protected mice from liver fibrosis. In a more fulminant hepatitis induced by injecting agonistic Fas-specific antibody, 82% of mice treated with siRNA that effectively silenced Fas survived for 10 days of observation, whereas all control mice died within 3 days. Silencing Fas expression with RNAi holds therapeutic promise to prevent liver injury by protecting hepatocytes from cytotoxicity.
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PMID:RNA interference targeting Fas protects mice from fulminant hepatitis. 1469 19

Antiviral therapy can now eliminate the hepatitis C virus in some 60% of all hepatitis patients. The results of recent studies have led to new recommendations for treatment: patients with HCV genotype I should be treated with pegylated interferons and 1000 or 1200 (patients weighing > 75 kg) mg ribavirin for 48 weeks, while patients with genotypes 2/3 should receive only 800 mg ribvavirin (irrespective of body weight) for 24 weeks. Data provided by two large drug-approval studies with PEG interferons alpha 2a and 2b show that the initial decrease in HCV-RNA determines the sustained viral response. Patients with genotype 1 have only a minimal chance (0-3%) of a sustained viral response if HCV-RNA is not reduced by at least a factor of 100 by the 12th week of treatment, and in these patients, treatment should then be discontinued. Pre-treatment determination of HCV genotype and HCV-RNA is mandatory to establish the chances of attaining a sustained viral response. Liver biopsy is necessary to determine the stage of disease and the urgency of treatment. In young persons with biochemical and histological inflammatory activity treatment is usually indicated. In asymptomatic older patients with no liver fibrosis, however, in particular those with a limited chance of a sustained viral response or concomitant disease, the indication for antiviral therapy is doubtful.
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PMID:[Only 1 injection per week brings a 60% chance of healing. New therapy recommendations in chronic hepatitis C]. 1263 35


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