Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of type C chronic hepatitis with the presence of epitheloid granulomas were reported. Case 1 was a 44-year-old man who presented with a moderate increase in serum ALT and positive anti-HCV. Histological examination of percutaneous liver biopsy specimens showed dense portal inflammation with piecemeal necrosis. Lobular inflammation was present mederately and a large well-organized epitheloid granuloma was found within a liver lobule. Case 2 was a 55-year-old woman, who was presented because of a slight increase in serum ALT and positive anti-HCV. Histologically, liver biopsy specimens showed lymphoid aggregates in the portal area and slight piecemeal necrosis. Moderate steatosis were noted and an epitheloid granuloma was present in the hepatic lobule. Acid-fast stains were negative for both cases and serum ACE and lysozyme were within normal range. These granulomas were composed of epitheloid cells surrounded by lymphocytes. They were not present within the portal tracts, but were found in the hepatic lobule. The incidence of the appearance of epitheloid granuloma in liver biopsy specimens of type C chronic hepatitis was 2 out of 273 cases (0.73%). The role of HCV infection in the genesis of epitheloid granulomatosis is of much interest and should be investigated.
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PMID:Epitheloid granuloma formation in type C chronic hepatitis: report of two cases. 759 May 82

The humoral response to the host cellular gene-derived epitope GOR (anti-GOR) was reported to be associated with chronic hepatitis C virus (HCV) infection. To determine the prevalence and clinical significance of anti-GOR, sera from 31 patients (M/F, 19/12, age 30-72) with chronic HCV infection (anti-HCV+ in 30, HCV-RNA+ by PCR in 31) were tested for anti-GOR by enzyme immunoassay. Results were correlated with clinical, biochemical and histological features, and the subsequent response to interferon-alpha therapy (a complete response was defined as normalization of serum ALT at the completion of therapy; a sustained response was defined as having normal serum liver biochemistry during the entire follow-up period). Anti-GOR was detected in 21 patients [67.7%, median optical density (OD) reading 2.634, range 0.865-3.000, cut-off value 0.300]. There was no correlation between the presence or the OD reading of anti-GOR and the clinical features (sex, age, mode of acquisition), biochemical tests (serum ALT, AST, alkaline phosphatase and albumin levels), autoimmune markers [serum globulin levels, anti-nuclear antibody (+ at < 1:80 in 6/31 patients)], and their subsequent response to interferon-alpha therapy (complete response in anti-GOR+ patients: 13/21, anti-GOR-: 5/10, p = NS; sustained response in anti-GOR+ patients: 5/21, anti-GOR-: 2/10, p = NS). There was also no correlation between anti-GOR and the histological features including Knodell score and its components including periportal inflammation, portal inflammation and fibrosis, the presence of lymphoid aggregates, macrovesicular and microvesicular fat, multinucleated hepatocytes, dysplasia, sinusoidal activity or bile duct lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of antibody to the host cellular gene derived epitope GOR in chronic hepatitis C virus infection. 752 85

Hepatitis C virus (HCV), a positive stranded RNA virus, is the main causative agent of post-transfusion and sporadic non-A non-B hepatitis worldwide. Paired samples of plasma and peripheral blood mononuclear cells (PBMC) from 11 patients with chronic hepatitis C treated with alpha-interferon (IFN) were tested, using a single step polymerase chain reaction (PCR), for the presence of HCV RNA. Before treatment, the viral genome was detected in all the plasma samples and 81.8% of PBMC. After 3 months of treatment, HCV RNA was still present in 63.6% of plasma samples but in only 27.3% of PBMC. A good correlation was observed between serum alanine aminotransferase level normalisation and disappearance of the viral genome in plasma. Among the six responder patients, five relapsed shortly after IFN withdrawal; HCV RNA became detectable again, especially in PBMC. These results show the presence of HCV in PBMC from most patients infected chronically. IFN therapy had an inhibitory effect on viral replication in lymphoid cells, but frequent relapses observed after cessation of treatment with IFN suggested persistence of HCV in these cells.
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PMID:Hepatitis C virus RNA in plasma and blood mononuclear cells in patients with chronic hepatitis C treated with alpha-interferon. 777 31

We studied hepatitis C virus carriers with normal liver function to evaluate the histological features of their livers and the replicative levels of hepatitis C virus. Liver biopsies were performed in 22 hepatitis C virus carriers with persistently normal ALT levels. Hepatitis C virus RNA in serum was quantified with a competitive assay that combined reverse transcription and the polymerase chain reaction, which is based on co-amplification of the target RNA with known amounts of synthetic mutated RNA. Three patients had normal livers on histological study, whereas the other 19 had chronic persistent hepatitis, with lymphoid infiltrates or aggregates in portal tracts commonly observed but intralobular inflammatory changes absent or minimal. The titer of hepatitis C virus RNA (logarithmic transformed copy number per milliliter of serum) varied from 4.0 to 8.0 (mean +/- S.D.: 6.3 +/- 1.1); it was significantly lower in the three patients with normal livers (4.3 +/- 0.2) than in those with chronic persistent hepatitis with mild (6.4 +/- 0.8, n = 11) or moderate (7.1 +/- 0.5, n = 8) portal inflammation. The titer of hepatitis C virus RNA was correlated with the total score (r = 0.68) and the score for portal inflammation (r = 0.68) in the histological activity index. These results indicated that there seem to be "healthy carriers" of hepatitis C virus with extremely low levels of viral replication. However, in most hepatitis C virus carriers with persistently normal ALT levels, there are inflammatory changes in the portal tracts, with severity depending on the replicative levels of hepatitis C virus.
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PMID:Serum hepatitis C virus RNA quantity and histological features of hepatitis C virus carriers with persistently normal ALT levels. 813 59

Hepatitis C virus (HCV) is an RNA virus that replicates in both the liver and lymphoid cells. Interferon-alpha (IFN-alpha) is a useful treatment of chronic hepatitis C (CHC) although resistance to this drug occurs frequently. The mechanisms underlying resistance to IFN remain unknown. In this work, we have measured the levels of glutathione in plasma and peripheral lymphoid cells from 15 healthy controls and 24 CHC patients, 10 of whom were without treatment and 14 showed high serum alanine aminotransferase (ALT) values despite therapy with lymphoblastoid IFN for more than 4 months. In all patients, glutathione levels in plasma and in mononuclear cells were depressed in comparison to controls. In IFN-unresponsive patients, the addition of 600 mg tid of oral N-acetyl cysteine (NAC), a glutathione precursor, resulted in a steady decrease of ALT values in all patients, with complete normalization in 41% of cases after 5-6 months of combined therapy. Administration of NAC alone for 1 month was without effect in the 10 patients that were not receiving IFN. Supplementation of IFN with NAC induced a near normalization of intralymphocytic glutathione, but plasma levels were only moderately increased. HCV replication was markedly inhibited in lymphocytes and viremia was cleared in one of the 8 patients tested. In conclusion, NAC enhances the response to IFN in CHC. Controlled studies are needed to ascertain whether antioxidant therapy might act in synergy with IFN in chronic viral hepatitis.
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PMID:N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. 822 88

Inflammation of the bile ducts was studied in liver biopsies from patients with chronic hepatitis C to determine whether the frequency of inflamed bile ducts changes with therapy and correlates with other histological variables and expression of class I and II MHC antigens on ductal epithelium. Twenty patients treated at UMMC between 1991 and 1994 underwent needle biopsies of the liver before and after therapy with interferon alpha 2B (IFN). A complete response to therapy was defined as a return to normal serum alanine aminotransferase levels occurring and persisting during therapy. The number of inflamed bile ducts/total ducts (%IBDs), presence of piecemeal necrosis and lymphoid aggregates, and grade of inflammation were assessed in each high-power field in all areas with bile ducts. The frequencies of these variables were compared in cirrhotics and non-cirrhotics and in patients with complete or incomplete responses to IFN. Frozen sections of biopsies from 5 patients were immunostained using antibodies to HLA-DR and B-2 microglobulin, and positive staining was noted on bile ducts. Before therapy, the %IBD was slightly greater in patients with cirrhosis. After IFN, both %IBD and serum alkaline phosphatase levels decreased in non-cirrhotics who responded to IFN. The change in frequency of IBD with IFN paralleled the changes in the other histological features. No correlation was noted between bile duct inflammation and expression of class I and II antigens. The conclusion is that inflammation of the bile ducts occurs frequently in chronic hepatitis C, correlates with other features of inflammation in the triads, and decreases in response to IFN therapy.
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PMID:Effect of interferon therapy on bile duct inflammation in hepatitis C. 876 34

The correlation between the histological features of liver biopsy specimens before interferon (IFN) treatment and the clinical effect of IFN administration on chronic hepatitis C was investigated. A study of the relation between several histological features that were graded in 60 liver biopsy specimens from chronic hepatitis C patients before IFN treatment disclosed that the grade of portal fibrosis was positively correlated with the grade of other inflammatory features, including piecemeal necrosis and portal and lobular inflammation. The degree of portal fibrosis adversely affected the rate of normalization of ALT levels in chronic hepatitis C during and after IFN treatment. We reexamined 36 liver biopsy specimens that showed a moderate degree of portal fibrosis, and found that the degree of piecemeal necrosis was inversely correlated with the extent of lymphoid follicle formation in the portal tracts. During IFN therapy, the group of chronic hepatitis C patients who showed marked piecemeal necrosis and less lymphoid follicle formation in the liver specimens had a poor response to IFN treatment, whereas another group that showed marked lymphoid follicle formation and little piecemeal necrosis in the liver specimens had a good response to IFN. These relationships gradually disappeared after the completion of IFN treatment.
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PMID:Assessment of histological features and outcome of interferon therapy in chronic hepatitis C. 880 31

Planar PCB congeners are embryotoxic and teratogenic to birds including American kestrels. The developmental toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was studied in the posthatching kestrel as a model for the eagle. Nestlings were dosed orally for 10 days with 5 microl/g body weight of corn oil (controls) or the planar PCB 126 at concentrations of 50, 250, or 1000 ng/g body weight. Dosing with 50 ng/g of PCB 126 resulted in a hepatic concentration of 156 ng/g wet weight, liver enlargement and mild coagulative necrosis, over 10-fold increases in hepatic microsomal ethoxyresorufin-O-dealkylase and benzyloxyresorufin-O-dealkylase, and approximately a 5-fold increase in methoxyresorufin-O-dealkylase. At this dose, mild to moderate lymphoid depletion of the spleen was apparent, as were decreased follicle size and content of the thyroid. At 250 ng/g, concentration of PCB 126 in the liver was 380 ng/g with increasing multifocal coagulative necrosis, decreased bone growth, decreased spleen weight with lymphocyte depletion of the spleen and bursa, and degenerative lesions of the thyroid. At 1000 ng/g, the liver concentration was 1098 ng/g, accompanied by decreased bursa weight, decreased hepatic thiol concentration, and increased plasma enzyme activities (ALT, AST, and LDH-L) in addition to the previous effects. Highly significant positive correlations were noted between liver concentrations of PCB 126 and the ratio of oxidized to reduced glutathone. These findings indicate that nestling kestrels are more susceptible to PCB 126 toxicity than adults, but less sensitive than embryos, and that planar PCBs are of potential hazard to nestling birds.
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PMID:Developmental toxicity of PCB 126 (3,3',4,4',5-pentachlorobiphenyl) in nestling American kestrels (Falco sparverius). 895 49

Hepatitis C virus (HCV) causes acute and often chronic hepatitis. On the basis of variations in nucleotide sequence, at least six genotypes and several subtypes have been identified. Histopathologically, chronic HCV infection is characterized by relatively mild hepatic inflammatory activity and a low degree of fibrosis, but hepatic lesions might be accompanied by bile duct damage, intraportal lymphoid aggregates, steatosis, or a combination of these manifestations. The histopathological lesions thus appear quite heterogeneous. To address the question of whether distinct histopathological manifestations are related to particular genotypes of HCV, 90 patients with chronic HCV infection were analyzed regarding histopathological features, biochemical liver parameters, demographic data, and virus genotype. The results revealed a significantly higher prevalence of both steatosis and bile duct lesions among patients infected by HCV type 3a compared to patients infected by types 1a or 1b. Furthermore, the data suggest interrelationships between virus genotype, patient's age, and a history of intravenous drug abuse. However, none of the histopathological manifestations were found to be related to a history of drug abuse. The data further corroborate the relationship of HCV type 1b infection to age, duration of disease, and the degree of fibrosis, respectively. Irrespective of HCV genotype, elevated serum ALT activity was shown to be associated with pronounced inflammatory activity or pronounced steatosis as well. Thus, the current data support the hypothesis that distinct genotypes of HCV appear to be associated with distinct manifestations of disease.
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PMID:Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype. 904 27

Assessment of chronic hepatitis C virus infection requires a liver biopsy in most circumstances. There is a reluctance to perform liver biopsy in haemophiliacs because of a perceived risk of haemorrhage, although with adequate factor concentrate replacement in patients without factor concentrate inhibitors it should be safe. We report a 4-year experience of liver biopsy in patients with haemophilia infected with chronic hepatitis C virus. Of 55 patients seropositive for anti-HCV, 35 have undergone liver biopsy; the median age of this group was 33 years (range 13-68). Seven patients had a normal liver. 22 had portal tract inflammation, four with lymphoid aggregates. Mild piece-meal necrosis was observed in only two and no bile duct injury was found. 11 patients had mild mixed micro- and macro-vesicular fat. 19 patients had no evidence of fibrosis despite an estimated median duration of disease of 20 years (range 8-43). In the remaining 16 patients the maximum degree of fibrosis achieved was stage III. Patients with more significant fibrosis could not be identified on the basis of ALT or HCV RNA. There were no complications of liver biopsy in this series. Liver biopsy following a well-defined protocol in chronic hepatitis C virus haemophiliac carriers is safe in the absence of factor concentrate inhibitors. In this young group of patients without HIV infection there was no evidence of significant liver disease despite a considerable duration of disease. Performing liver biopsy allows accurate information to be given to the patient and avoids unnecessary therapy. The relative youth of this group may be important in the light of the benign histology.
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PMID:The role for liver biopsy in haemophiliacs infected with the hepatitis C virus. 935 33


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