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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.
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PMID:Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292. 893 68

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

A 51-year-old man presented with severe anemia, mild splenomegaly and elevated serum aspartate aminotransferase and serum alanine aminotransferase levels. The bone marrow findings were consistent with pure red cell aplasia (PRCA) with a 'maturation arrest' at the level of pronormoblast. The patient has been transfusion-dependent for 8 months. Following diagnosis of chronic active hepatitis due to hepatitis C virus (HCV), therapy with interferon-alpha was initiated. Two weeks later, the hemoglobin level stabilized, and he has not required any transfusion ever since. In spite of ongoing HCV viremia, cessation of interferon therapy, and deterioration of the liver function tests, the patient, followed for 2 years, maintains a high-normal hemoglobin level. To the best of our knowledge, this is the first report of prolonged PRCA corrected by interferon-alpha therapy, with or without an ongoing HCV infection. We speculate that the 'maturation arrest' of the erythroid lineage seen in the bone marrow was the result of an immune mechanism, possibly induced by the HCV, and that the elimination of this mechanism, rather than the elimination of the HCV, provided the opportunity for regeneration of erythropoiesis.
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PMID:Pure red cell aplasia responsive to interferon-alpha in a patient with hepatitis C virus infection. 997 47

The prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection ranges from nearly 30% to over 50%, depending on the population. Shared modes of transmission and the success of current antiretroviral regimens have contributed to the emergence of HCV as a significant pathogen in the HIV-positive population. HIV coinfection appears to worsen HCV infection, with studies showing more severe fibrosis, a higher frequency of cirrhosis, and increased deaths from liver disease. HIV coinfection may also increase the rate of maternal-fetal transmission of HCV. Similarly, studies suggest a more rapid progression to AIDS or death for HCV genotypes 1a and 1b than for other genotypes in HIV-infected patients with hemophilia. Highly active antiretroviral therapy (HAART), such as HIV protease inhibitors, has no effect on HCV infection and may transiently increase ALT, AST, and hepatitis C viral load. Hepatotoxicity associated with HAART may or may not be related to the presence of HCV and may depend on the specific agents used. Data suggest that treating chronic hepatitis C in HIV-co-infected patients can decrease fibrosis, increase T-cell responsiveness to HCV antigens, and decrease the rate of fatal hepatomas. Interferon alpha may provide sustained biochemical or virologic responses in HIV/HCV-coinfected patients. The combination of interferon-alpha and ribavirin may also be a treatment option but is more complex, and additional research is needed. Treating HCV infection in HIV/HCV-coinfected individuals may help lower the hepatitis C viral load and permit treatment with protease inhibitors.
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PMID:Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. 1065 64

To develop prognostic models for identifying children with hepatitis B who are likely to respond to interferon-alpha (IFN-alpha) or to spontaneously seroconvert, we evaluated results of a multinational controlled trial comprising 70 children with chronic hepatitis B who received IFN-alpha and 74 children who did not receive therapy. Prognostic models were developed using SMILES (similarity of least squares), which is a data analysis network that incorporates multidimensional relationships in the clinical data of complex diseases. Commonly collected clinical data included age, gender, serum aminotransferase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hepatitis B virus (HBV) DNA levels, and IFN-alpha dose. Additional data included pretreatment directional information (e.g. increases or decreases in serum aminotransferase and HBV DNA levels), liver biopsy results, race and transmission mode. Using data available prior to initiation of treatment, the SMILES models achieved prospective predictions of 89% for responders, 96% for non-responders, 100% for seroconverters and 93% for non-seroconverters. Although not predictive by themselves, the variables that had the greatest impact on predictions for IFN-alpha response were HBV DNA pretreatment direction, baseline HBV DNA, IFN-alpha dose and gender. The variables that had the greatest impact on predictions for spontaneous seroconversion were ALT pretreatment direction, baseline HBV DNA level, age and AST pretreatment direction. Therefore, these models may be useful in determining, in children with hepatitis B, the likelihood of response to IFN-alpha and spontaneous seroconversion.
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PMID:Statistical models for predicting response to interferon-alpha and spontaneous seroconversion in children with chronic hepatitis B. 1076 45

The serum protein designated 90K/Mac-2BP has been found at elevated concentrations in the sera of patients with various types of cancer and viral infections. The importance of the 90K/Mac-2BP serum concentrations in predicting the response towards interferon-alpha treatment for hepatitis C virus (HCV) infection prompted us to utilize a new ELISA for soluble human 90K/Mac-2BP to monitor the serum concentrations of this protein in our HCV-positive patients. Seventy HCV-PCR and anti-HCV antibody positive patients were analyzed for their serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, cholinesterase, HCV-viral load, viral subtypes, and 90K/Mac-2BP. On correlation of age and 90K/Mac-2BP levels, we found an apparent correlation that was proved rather to be a strong dependence of 90K/Mac-2BP concentrations on disease severity/duration, which increases with age. Multiple correlation analysis demonstrated the independent nature of 90K/Mac-2BP concentrations, underscoring the potential high utility of this new marker. Our data corroborate the potential of the scavenger receptor family protein 90K/Mac-2BP as an independent predictor of disease severity during HCV infection.
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PMID:Serum protein 90K/Mac-2BP is an independent predictor of disease severity during hepatitis C virus infection. 1090 55


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