Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of widely differing reports on the significance of IgM anti-HBc in chronic hepatitis B virus (HBV) infection, paired sera and liver biopsies from 49 patients with chronic HBV infection were analysed for serum IgM anti-HBc, HBsAg titre, HBeAg/anti-HBe, HBV DNA, serum aspartate transaminase, intrahepatic HBcAg expression, and liver histology. High levels of IgM anti-HBc, in the diagnostic range of acute hepatitis B (greater than 1.2), were detected in seven patients (14.3%) and a total of 34 patients (69.6%) had an index of more than 0.2. No correlation was found between IgM anti-HBc and the serum markers of active viral replication or HBsAg titre but it correlated significantly with intrahepatic expression of cytoplasmic HBcAg (r2 = 0.165, P = 0.002). IgM anti-HBc also correlated with active liver histology (P = 0.015) but there was a considerable overlap of the IgM anti-HBc index values between the various disease groups, indicating a poor specificity. Serial assessment of IgM anti-HBc in eight patients treated with interferon-alpha (four responders) showed an increase in IgM anti-HBc in three out of four patients corresponding to the e-seroconversion period followed by a drop in IgM anti-HBc levels. However, an increase in IgM anti-HBc was also seen in one non-responder, indicating that this feature is not unique to interferon-alpha responders. These data indicate that serum IgM anti-HBc cannot be used alone as a certain diagnostic measure of HBV replication nor in the prediction of liver histology.
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PMID:Significance of serum IgM anti-HBc in chronic hepatitis B virus infection. 157 87

A total of eight patients with chronic active HBsAg-positive hepatitis was treated with recombinant interferon-alpha 2b for 12 months and serum aspartate aminotransferase, alanine aminotransferase, gamma-globulin and prolyl hydroxylase concentrations were determined every 3 months. Liver biopsies after 12 months' treatment revealed a significant (P less than 0.05) reduction in the histological activity score. After 6 months, alanine aminotransferase (P less than 0.01) and aspartate aminotransferase (P less than 0.05) concentrations fell significantly compared with baseline concentrations. Serum prolyl hydroxylase concentrations declined significantly (P less than 0.05) after 15 months and remained depressed. It is concluded that interferon-alpha 2b therapy reduced fibrogenetic activity in chronic active hepatitis B.
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PMID:Modifications in the serum concentrations of prolyl hydroxylase in patients with chronic hepatitis B during and after interferon therapy. 169 25

In a randomized controlled trial, 41 chronic hepatitis B virus carriers were allocated, by opening numbered computerized randomization envelopes, to receive recombinant interferon-alpha 2A at three different doses: 2.5; 5.0, and 10.0 mU per m2. Thirty-two patients received treatment (6 for 3 months, 26 for 6 months), and 9 patients were controls (received no treatment). Ninety-three per cent of our patients were homosexual, and 41% had anti-HTLV-III in their serum. None of the control patients lost HBeAg. In contrast, six of the anti-HTLV-III-negative patients (33%) responded to treatment (p less than 0.02): five of these responders were homosexual (p less than 0.05). The response rate was greatest (44%) in the anti-HTLV-III-negative patients who received 10 mU per m2 of recombinant interferon-alpha 2A. None of the anti-HTLV-III-positive patients responded to treatment. The percentage reduction of hepatitis B virus DNA was significantly less in the anti-HTLV-III-positive group in comparison to the anti-HTLV-III-negative group at 1 and 4 months of treatment and at 3 months after the end of treatment (p less than 0.05). These patients were younger (33 vs. 42 years, p less than 0.02), had lower mean baseline AST values (42 vs. 80 IU per liter, p less than 0.02) and tended to have milder histological disease. Homosexual men with HBeAg-positive chronic liver disease who are anti-HTLV-III-positive appear to be less responsive to the direct antiviral and immunomodulatory effects of recombinant interferon-alpha 2A. This may be due to the subclinical immunosuppressive effects of co-infection with HTLV-III.
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PMID:Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha-interferon. 303 22

For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in more than 40 percent of patients treated with combination therapy, 30 percent with interferon therapy, 18 percent with acyclovir, and 0 percent with no treatment. HBe reactivation occurred in two patients with cirrhosis. Hepatitis B surface seroconversion followed HBe seroconversion in 11 to 30 percent of treated patients. HBe seroconversion was significantly related to initial low levels of viral replication and to transient aminotransferase elevation during the second half of the interferon treatment of 16 weeks. Clinical improvement and persistent normalization of aspartate aminotransferase was observed in all patients with HBe seroconversion. Conversion to a state of virus latency (HBe negative) mostly occurred after therapy, suggesting that the specific immunologic host response had been brought about by the suppression of virus replication through antiviral agents. Recommendations for selection of patients for antiviral combination therapy are made on the basis of these long-term results.
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PMID:Long-term follow-up of antiviral combination therapy in chronic hepatitis B. 304 80

It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-alpha (IFN-alpha) therapy in chronic hepatitis C virus (HC) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 27 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.27 +/- 0.12 micrograms ml-1, HCV 1.62 +/- 0.11 micrograms ml-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 +/- 0.007 U ml-1, HCV 0.230 +/- 0.007 U ml-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.
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PMID:Plasma glutathione concentration in patients with chronic hepatitis C virus infection. 748 49

To determine the prevalence and clinical significance of IgM and IgA antibody to hepatitis C virus (HCV) core antigen in chronic HCV infection, sera from 47 patients were tested for immunoglobulin class M (IgM) and immunoglobulin A (IgA) antibody to HCV core antigen by solid-phase enzyme-linked immunoassay using a recombinant core protein (aa1-150). Results were correlated with the clinical, biochemical and histological parameters, serum HCV RNA levels (determined by branched DNA signal amplification assay), and subsequent clinical response to interferon-alpha therapy. IgM anti-HCV core was detected in 11 patients (23.4 percent). There was no correlation between the presence of IgM anti-HCV core and the clinical features (sex, age, mode of acquisition), biochemical parameters (serum ALT, AST, alkaline phosphatase, and albumin level), autoimmune markers [serum globulin levels, anti-nuclear antibody (+ at < 1:80 in 7/47 patients)], serum HCV RNA levels, subsequent response to interferon-alpha therapy, and the histological features. Immunoglobulin A anti-HCV core was not detected in any of the patients. The presence of IgM ant-HCV core in a proportion of patients with chronic HCV infection indicates that the presence of serum IgM anti-HCV core may not be unique to acute HCV infection.
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PMID:Immunoglobulin M and A antibodies to hepatitis C core antigen in chronic hepatitis C virus infection. 752 59

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

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.
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PMID:Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy. 791 Jul 16

Interferon-alpha induces remission in 30% to 40% of patients with chronic hepatitis B, but its effect on hepatic connective tissue turnover has not been well documented. We studied the changes in serum procollagen III propeptide and laminin-P1 peptide (Lam-P1) in 33 patients with chronic hepatitis B (11 nontreated controls and 22 treated patients) during a 4-mo randomized trial of interferon-alpha. Liver biopsy specimens were obtained at the start of treatment and 12 mo later. Liver biochemical tests, procollagen III propeptide, laminin-P1 peptide and hepatitis B virus DNA polymerase were determined before treatment with interferon was begun (mo -3), at the initiation (0 time) and completion of treatment (mo 4) and also at 8, 12 and 18 mo. Treated patients were classified as "responders" and "nonresponders" on the basis of clearance of HBV e antigen from serum. There were no significant changes in the control group, whereas the responders had persistent decreases in ALT, AST, hepatitis B virus dna polymerase, procollagen III propeptide and laminin-P1 peptide. The nonresponders had transient ALT, AST and hepatitis B virus dna polymerase reductions that returned toward baseline levels during follow-up, but procollagen III propeptide and laminin-P1 peptide persisted below the baseline at mo 18. Significant correlations between procollagen III propeptide and laminin-P1 peptide with ALT, AST and liver histologic specimens were noted at baseline but not after 12 mo. Changes in procollagen III propeptide levels also correlated with changes in AST, ALT and liver histologic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in serum levels of markers of hepatic connective tissue turnover during and after treatment of chronic hepatitis B with interferon-alpha. 813 56

Serum IgM anti-HBc was determined in 135 chronic HBsAg carriers with various categories of histological activity on liver biopsy and hepatitis B serological profile. Thirty-three patients were treated with interferon-alpha to investigate the correlation between serum IgM anti-HBc with histological activity and viral replication, to evaluate the usefulness of pretreatment IgM anti-HBc as a predictor of a successful response to interferon-alpha and to examine the IgM anti-HBc response during this treatment. All 53 patients with chronic active hepatitis with either wild-type (n = 42) or precore mutant variant HBV infection (n = 11) had an IgM anti-HBc index greater than 0.300 compared with 7.4% (2 of 27) of the chronic HBsAg/HBeAg-positive carriers with chronic persistent hepatitis, 10% (3 of 30) of the anti-HBe-positive asymptomatic carriers and none of the 25 patients with hepatitis D virus-positive chronic active hepatitis (p < 0.0001). Pretreatment IgM anti-HBc index was greater than 0.300 in 82.4% (14 of 17) of HBeAg/HBV DNA-positive patients who seroconverted after interferon-alpha treatment compared with 25% (4 of 16) of the patients who did not seroconvert (p = 0.0013), whereas an elevated pretreatment AST was present in only 52.9% (9 of 17) of responders and in 37.5% (6 of 16) of nonresponders (p = 0.42). Serial testing of IgM anti-HBc in these 33 patients during interferon-alpha treatment showed a significant rise in IgM anti-HBc in all responders, which followed the AST flare-up but preceded the time of the HBeAg to anti-HBe seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative assessment of serum IgM anti-HBc in the natural course and during interferon treatment of chronic hepatitis B virus infection. 829 88


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