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)

We developed a nonradioisotopic assay for detection of hepatitis delta virus RNA in serum by combining reverse transcription of RNA, polymerase chain reaction of the resultant complementary DNA and enzyme linked immunoassay detection of the polymerase chain reaction products using a monoclonal antibody specific for double-stranded DNA. This DNA enzyme immunoassay had a limit of detection of cloned hepatitis delta virus RNA similar to that of standard PCR followed by Southern-blot hybridization (approximately 10 copies/sample) and was 10(3) to 10(4) times more sensitive than direct dot-blot hybridization (approximately 10(5) copies/sample). Serial serum samples from six patients with chronic hepatitis delta virus infection undergoing interferon therapy were analyzed by reverse transcription-polymerase chain reaction followed by both standard hybridization and DNA enzyme immunoassay. The results of both methods were comparable, revealing disappearance of hepatitis delta virus RNA after 3 to 6 mo of therapy in three patients, two of whom had also a significant decrease in ALT activity. The DNA enzyme immunoassay test is therefore a potentially useful method for therapeutic monitoring in chronic hepatitis delta virus infection and may contribute to a wider application of polymerase chain reaction in clinical laboratories.
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PMID:Evaluation of hepatitis delta virus RNA levels during interferon therapy by analysis of polymerase chain reaction products with a nonradioisotopic hybridization assay. 137 82

Liver and serum samples from 67 children with hepatitis B chronic infection, whether or not treated with recombinant interferon, were analyzed for the presence of hepatitis B virus DNA. After follow-up, 44/67 (66%) still had serum and liver viral DNA; 23/67 (34%) were negative for serum hepatitis B virus DNA. Of the 23 children in the latter group, liver biopsy was available in 21 and viral DNA was not detected by Southern-blot in 20. In the remaining patient, viral DNA was in an episomal nonreplicative form. Polymerase chain reaction was performed in the 21 serum samples negative for viral DNA by conventional techniques and in the 21 liver samples (20 negative for hepatitis B virus DNA and 1 with episomal nonreplicative form). All liver samples resulted in a positive reaction to viral DNA by this technique. Serum viral DNA by polymerase chain reaction was detected in 15/21 (71%) of these patients. The mean of alanine aminotransferase values was similar in patients with or without hepatitis B virus DNA in serum by polymerase chain reaction. In summary, in the majority of the patients who respond to the therapy, there is a persistence of viral replication detected by polymerase chain reaction. This fact explains the persistence of serum HBsAg in these patients. However, more studies are necessary to determine the meaning of the presence of hepatitis B virus DNA that is only detectable by polymerase chain reaction.
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PMID:Persistence of hepatitis B virus DNA after reduction of viral replication in serum and liver. 138 16

A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.
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PMID:Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis B. 138 10

The effects of interferon therapy on liver histologic findings were assessed in a randomized controlled trial consisting of 80 patients with chronic non-A,non-B hepatitis. Twenty-eight patients received 1 million units of recombinant interferon alpha-2b; 25 patients received 3 million units, subcutaneously, three times a week for 24 weeks; and 21 patients were observed as untreated controls; all of them underwent liver biopsy within 6 months from the beginning of the study and on the last day of therapy. Six patients were withdrawn from the study because of inadequate liver biopsy specimens. Alanine aminotransferase levels were determined before, during, and after therapy. For each biopsy, a semiquantitative score of histologic features, the histologic activity index, and the overall histologic assessment were performed. Ninety-five percent of patients tested positive for hepatitis C virus antibody. Portal inflammation, piecemeal and spotty necrosis, and bile duct proliferation were significantly decreased in patients with normalized alanine aminotransferase. The effectiveness of therapy was dose dependent: piecemeal and spotty necrosis and the histologic activity index showed a significant decrease only in 3-million-unit-treated patients. Hepatocellular degeneration and fibrosis did not change significantly after treatment.
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PMID:Histologic changes in liver biopsy specimens produced by recombinant interferon alpha-2b therapy for chronic non-A,non-B viral hepatitis. A randomized controlled trial. 141 21

About one third of patients with chronic hepatitis B show a sustained response when treated with interferon-alpha. Combining interferon-alpha with immunomodulators might be a way to increase response rate. The aim of this study was to compare the efficacy of lymphoblastoid interferon-alpha given alone with its efficacy when combined with levamisole in chronic hepatitis B. Forty-five patients with HBeAg-positive chronic hepatitis were randomly selected (with stratification for ALT levels) to receive a 6-mo course of combination therapy with lymphoblastoid interferon-alpha (5 million units/m2 three times per week) and levamisole (150 mg three times per week) or lymphoblastoid interferon at the same dose regimen and a matching placebo. Final evaluation 18 mo after randomization revealed a loss of both HBeAg and hepatitis B virus DNA with ALT normalization in 38% of patients treated with interferon-alpha alone and in 10% of patients receiving combination therapy. The higher response rate observed in patients treated with interferon-alpha alone was maintained after stratification for basal ALT levels (i.e., higher [45% vs. 10%] or lower [31% vs. 9%] than three times the upper normal value). The length of time to sustained HBeAg clearance was significantly (p < 0.05) shorter in patients receiving monotherapy than in patients receiving combination therapy. Blinded histological assessment revealed improvement in 44% of patients treated with interferon-alpha alone compared with improvement in 6% of patients receiving combination therapy. These results indicate that levamisole has no additive effects when combined with interferon-alpha in the treatment of HBeAg-positive chronic hepatitis.
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PMID:Therapy for chronic hepatitis B with lymphoblastoid interferon-alpha and levamisole. 142 52

We studied gamma-interferon production of phytohemagglutinin-stimulated peripheral blood mononuclear cells in response to alpha-interferon in hepatitis B virus carriers and healthy individuals. The magnitude of gamma-interferon production was significantly higher in patients with anti-HBe antibody than in patients with HBe antigen and healthy individuals. Furthermore, alpha-interferon augmented the production of gamma-interferon of peripheral blood mononuclear cells from patients with active liver injury [serum alanine aminotransferase (ALT), greater than 40 U/L], but not that from patients with inactive liver injury (serum ALT, less than 40 U/L) or healthy individuals. These results suggested that alpha-interferon could enhance the cellular immune response against hepatitis B virus by augmenting the endogenous production of gamma-interferon in patients with active liver injury, implying that the responsiveness to alpha-interferon might be responsible for liver cell injury.
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PMID:Effects of alpha-interferon on gamma-interferon production of peripheral blood mononuclear cells in hepatitis B virus carriers. 143 Jan 5

Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B (CHB) were randomly assigned to receive human lymphoblastoid interferon (ly-IFN) at a dose of 5 MU/m2 i.m. three times a week for 6 months (ten cases) or no treatment (eight cases). All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy. During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels, and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values. None of the untreated patients became persistently HBV-DNA-negative or showed significant variations of ALT levels. During the post-treatment follow-up, from 1 to 17 months after ly-IFN discontinuation, eight of the nine responders (89%) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity, with an ALT peak in four of them. On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen. Histological features improved in four treated patients, worsened in one untreated case and were unchanged in the remaining patients. These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti-HBe- and HBV-DNA-positive CHB. The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation.
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PMID:Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon. 150 Jun 86

We evaluated titers of C100-3 antibody by ELISA using a 4-parameter logistic fitting curve and examined the transition of the values in the cases of interferon treatment. The 4-parameter logistic fitting curve produced a standard curve in a wider range using a micro plate reader than the logarithmic curve. The values of C100-3 antibody during and after the treatments of interferon were changed in parallel with the alterations of ALT. The anti-C100-3 antibody titers assayed in the complete or partial responders were significantly reduced at the end of interferon therapy. These findings suggest the clinical usefulness of the evaluation of anti C100-3 antibody titers.
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PMID:[Anti-C100-3 antibody titration using 4-parameter logistic curve (results in its application to hepatitis C cases treated with interferon]. 151 34

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p less than 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p less than 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response. The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously.
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PMID:A randomized controlled trial of lymphoblastoid interferon-alpha in patients with chronic hepatitis B lacking HBeAg. 155 34

In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.
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PMID:A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. 158 29


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