Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

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

Interferon-alpha therapy leads to HBeAg seroconversion in only one third of patients with chronic hepatitis B. In an attempt to increase the seroconversion rate, we investigated the combination of interferon-alpha and zidovudine in a subset of patients with presumably low response rates for interferon-alpha monotherapy. In a double-blind, controlled trial, 24 HBeAg-positive patients were randomized to receive lymphoblastoid interferon-alpha in subcutaneous doses increasing to 5 MU daily, combined with zidovudine given orally in doses increasing from 500 to 1,000 mg/day or with placebo for 16 wk. Treatment effects were monitored by quantitative assessment of HBV DNA, HBeAg and HBV DNA polymerase. Six months after termination of therapy, 1 of 12 (8%; 95% confidence interval = 2% to 39%) patients treated with interferon-alpha plus zidovudine and 2 of 12 (17%; 95% confidence interval 2% to 48%) patients from the control group exhibited responses (HBeAg seroconversion). All patients remained HBsAg positive. The only responder of the interferon-alpha-zidovudine group relapsed after cessation of therapy, so none of the zidovudine-treated patients were HBeAg negative at the end of follow-up. No significant difference in AST level or in any of the virological markers was observed between the two groups during the course of the study. Adverse effects (anemia, leukopenia) necessitated reduction in the dose of zidovudine in 50% and of interferon-alpha in 42% of the patients treated with interferon-alpha plus zidovudine; in the control group these rates were 0% for placebo and 8% for interferon-alpha. In conclusion, the antiviral effect of interferon-alpha in chronic hepatitis B was not enhanced by additional zidovudine treatment. The combination therapy induced considerable side effects leading to dose reduction for both zidovudine and interferon-alpha. For combination therapy with interferon-alpha, oral nucleoside analogs with more potent antiviral effects and less toxicity than zidovudine should be developed.
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PMID:Interferon-alpha and zidovudine combination therapy for chronic hepatitis B: results of a randomized, placebo-controlled trial. 844 11

Nineteen haemodialysis (HD) patients with chronic hepatitis C were treated with interferon-alpha 2b (IFN-alpha) at a dose of 3 or 1 MU thrice weekly for 6 months and were followed-up for another 14 months without treatment. Six patients discontinued treatment because they either presented severe side-effects to IFN-alpha or had complications of their primary disease. Levels of AST and ALT were within normal limits on the 2nd month of treatment and remained so throughout the treatment and the follow-up period in all patients except one who showed an elevation of transaminase levels 2 months after the end of treatment. Serum HCVRNA became negative in 10/13 patients at the end of treatment and was negative in all patients on the 6th month and in 12/13 patients on the 14th month during the follow-up period. Levels of 2'5' oligosynthetase were increased significantly on the 2nd and 4th month of treatment and returned to pretreatment values the 2nd month after treatment. These findings demonstrate that haemodialysis patients with chronic hepatitis C respond well to interferon treatment and that a long-term response is achieved in a high proportion of patients.
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PMID:Interferon-alpha 2b treatment of chronic hepatitis C in haemodialysis patients. 859 90

Hepatitis C virus infection causes acute and often chronic hepatitis. Therapy with interferon-alpha has been shown to induce remission of the inflammatory process within the liver and also elimination of the virus. However, only about 50% of treated patients respond in terms of at least a transient disappearance of viral RNA from the circulation below the limit of detection. In order to find prognostic factors for responsiveness, patients with chronic hepatitis C virus infection were analyzed for virus genotype and pretreatment biochemical liver parameters including serum AST, ALT, and gamma-GT activities. Whereas the initial biochemical response to interferon-alpha 2a was found not to be related to virus genotype, the initial virological response was found to be closely related to infection by genotype 3a and to a low pretreatment ratio of serum gamma-GT/ALT activity. These data confirm and extend the importance of virus genotype for responsiveness to interferon-alpha therapy and introduce an additional, host-specific parameter with a potential predictive value, namely the pretreatment ratio of serum gamma-GT/ALT activity.
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PMID:Preferential virological response to interferon-alpha 2a in patients with chronic hepatitis C infected by virus genotype 3a and exhibiting a low gamma-GT/ALT ratio. 865 61

To determine the clinical significance of viral quasispecies heterogeneity, 59 patients with chronic hepatitis C were studied using singlestranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1); of these, 48 were subsequently treated with interferon-alpha. The SSCP method was validated using clones of known nucleotide sequence. HVR1 was amplified in 54 of 59 (92%) patients. The median number of SSCP bands per sample was 6 (range: 2-12). Increased quasispecies heterogeneity correlated with the estimated duration of HCV infection (P < 0.05), parenteral-acquired HCV infection (vs. sporadic, P < 0.05), serum HCV RNA levels (P < 0.05), and HCV genotype 1 infection (P < 0.05), but not with age, serum AST, ALT, or Knodell score. Patients who had complete and sustained response to interferon-alpha (n = 11) had lower pre-treatment quasispecies heterogeneity compared to patients who had complete response with relapse (n = 18, P < 0.05) or no complete response (n = 16, P < 0.01). However, multivariate analysis revealed that HCV viremia was a stronger predictor of response to interferon-alpha. These findings indicate that the estimated duration of HCV carriage, serum HCV RNA levels, and HCV type 1 are important determinants for the evolution of HCV quasispecies heterogeneity; and that increased HCV quasispecies heterogeneity is another marker associated with a poor subsequent response to interferon-alpha.
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PMID:Clinical implications of viral quasispecies heterogeneity in chronic hepatitis C. 881 72

We evaluated the impact of concomitant infection with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) on the clinical course after renal transplantation (Tx). In 335 patients (pts) transplanted between 1991 and 1993 we found 30 (9%) recipients who were positive for Hepatitis B surface antigen (HBsAg) (ELISA, Organon) and anti-HCV antibodies (immunoblot assay Lia Tek) preTx. Chronic liver disease (CLD) (two-fold or greater increase in serum ALT and AST levels for at least six months) developed in 40.7% coinfected pts as compared to 24.4% and 25.7% pts infected only with HCV or HBV, respectively. Maintenance immunosuppression consisted of P + Aza + CsA, mean follow-up time was 28 +/- 15 months. The mean time of the onset of CLD was 3.0 months (range: 1-18 months) after Tx. Percutaneous liver biopsy performed in 5 CLD pts revealed chronic active hepatitis (CAH) in 4 and chronic persistent hepatitis (CPH) in 1 pt. Four pts who had CAH and were positive for HCV RNA (RT PCR) in serum and for HBcAg in liver tissue, received interferon-alpha therapy for 6 months. Clinical improvement of liver function was observed in all of them, but none cleared HBsAg or HCV RNA. One pt lost his graft due to acute rejection. Concomitant infection with HBV and HCV is associated with the high risk of development of CLD early after Tx. We recommend that pretransplant evaluation of both anti-HCV and HBsAg positive pts should include liver biopsy to exclude potential recipients with CAH.
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PMID:Clinical course of concomitant Hbv and Hcv infection in renal allograft recipients. 986 22


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