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)

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid alpha-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg), 'e' antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2-6 weeks after prednisolone withdrawal, loss of HBV-DNA 0-8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.
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PMID:Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection. 836 39

In about 30% to 40% of patients with chronic hepatitis C, treatment with recombinant interferon alfa (r-IFN alpha) causes a decrease of serum aminotransferases and hepatitis C virus (HCV) RNA. The antiviral mechanism of interferon alfa (IFN alpha) in vivo is unknown. From serial measurements of serum HCV-RNA concentrations following IFN alpha induced perturbation of the balance between virus production and clearance, we obtained kinetic information on the pretreatment steady-state of HCV. In patients with chronic hepatitis C responding to IFN alpha, HCV-RNA declined exponentially with a half life of approximately 2 days. Modeling of the data predicts that in patients with chronic hepatitis C responding to IFN alpha this cytokine predominantly acts as an inhibitor of de novo infection of susceptible cells. HCV is released from infected cells with a mean half life of 2.7 +/- 1.3 days, whereas the clearance rate from serum is faster (mean half life, 0.7 +/- 0.4 days). The minimum virus production and clearance per day in patients with chronic hepatitis C was calculated to be 6.7 x 10(10) virions/d (range, 0.2 to 43.8 x 10(10) virions/d). These values showed no correlation with the HCV genotype, aminotransferase levels, or the histological activity as assessed before the administration of r-IFN alpha. Simultaneous kinetic analysis of serum aminotransferases as surrogate markers of hepatocyte integrity revealed half lifes for the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from hepatocytes of 4.7 +/- 3.8 and 3.0 +/- 3.5 days, respectively. The half life data for HCV in chronically infected patients are remarkably similar to recently published data on human immunodeficiency virus type 1 (HIV-1) suggesting that both RNA viruses replicate continuously and highly productive in vivo. The turnover rates explain the rapid generation of viral diversity and the opportunity for viral escape phenomena from the host immune surveillance.
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PMID:Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo. 859 65

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

Twenty patients with chronic B hepatitis and viral replication were included in a randomized study comparing the efficacy of sequential treatment with prednisone for 6 weeks followed by alpha-2a interferon (IFN) for 6 months (group A, 9 cases), versus concomitant administration of both drugs (group B, 11 cases). There were no significant differences between the two groups regarding age, sex, AST, ALT, DNA-VHB values, index of histological activity or type of underlying chronic hepatitis. Two patients from each group were excluded. The mean follow-up of the patients was 22.2 months. In group A, four responses were achieved (57.1%), of which 2 were complete and 2 partial. The overall response rate in group B was 77.7% (7 cases), 6 of them were complete responses (66.7%). Among HBsAg-positive patients from group B, one seroconverted to anti-HBs. A total of 7 patients with anti-HBe were included in the study. Two belonged to group A, in which a partial response was achieved, and another 5 were in group B, with 4 reaching a complete response and one reaching a partial response. There were no statistical differences with regards to the type of response in both groups. The AST, ALT values, as well as the pre-treatment levels of DNA-VHB, showed a significant statistical association with the response (p < 0.05). In all patients responding to treatment a histological improvement was observed that became even more evident in the biopsy performed 12 months after IFN withdrawal. In conclusion, concomitant therapy with prednisone and IFN is as effective as sequential therapy in the treatment of chronic B hepatitis. The results achieved with concomitant therapy suggest that new controlled trials are need to establish if this therapeutic schedule is the elective treatment in chronic B hepatitis.
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PMID:[Comparison of 2 treatment strategies with prednisone and interferon in chronic hepatitis B]. 864 11

The comparative efficacy of prednisolone followed by interferon alfa (IFN-alpha) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89 percent] white), all having inflammatory changes on liver biopsy. Patients were randomized to receive either prednisolone followed by IFN-alpha (n = 34); placebo followed by IFN-alpha (n = 30); or no treatment (n = 31). The prednisolone/placebo was given on a double-blind basis. Lymphoblastoid IFN-alpha was given at 5 MU/m(2) three times a week for 12 weeks. Baseline clinical, biochemical, and histological features were similar for the three groups. The majority (85 percent) had a baseline aspartate aminotransferase (AST) level < or = 100 IU/L. On follow-up between 12 and 18 months (median, 15 months) after treatment, the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids (12 of 34 [35 percent]) or placebo [12 of 30 (40 percent)] as against controls (4 of 31 [13 percent], P< .05). Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treatment with IFN-alpha, at the dose and duration used in this study, improves the rate of anti-HBe seroconversion. Steroid priming does not potentiate the effect of IFN-alpha.
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PMID:Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial. 866 20

The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30 IU/l) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10(2) to 10(7) copies/50 microliters serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.
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PMID:Circulating HCV-RNA, HCV genotype, and liver histology in asymptomatic individuals reactive for anti-HCV antibody and their follow-up study. 887 94

An open label trial of GM-CSF plus high-dose interferon (IFN) alpha 2b was performed in eight patients with chronic hepatitis B infection and 16 patients with chronic hepatitis C, who either failed to clear virus with 6 months of daily high-dose IFN (5 MU daily) therapy (n = 22) or were considered untreatable because of advanced disease and leukopenia (n = 2). The dose of GM-CSF used was 500 micrograms subcutaneously twice weekly. The dose of IFN used was 5 MU daily. Both agents were administered for 4 months. Five of the eight hepatitis B patients and five of the 16 hepatitis C virus patients responded to combined therapy having previously failed IFN therapy alone. The hepatitis B virus responders had low entry ALT, AST, and gamma GPT levels as compared to the non-responders. No such differences for responders and non-responders were seen with the hepatitis C virus patients. These data suggest that the combination of GM-CSF and IFN may be more effective at achieving viral clearance than IFN alone.
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PMID:A preliminary experience with GM-CSF plus interferon in patients with HBV and HCV resistant to interferon therapy. 909 87

Treatment of chronic hepatitis C with alfa interferon for 6 months achieves sustained responses in 15-25% of the patients. The initial induction with higher doses and the prolongation of treatment can improve the results. A randomized, prospective study was carried out to compare the efficacy of a short term induction schedule of interferon alfa-2b (group A) versus a long term one (group B). 106 patients with chronic hepatitis C were included: 54 received 5 megaunits tiw for 8 weeks and 52 for 16 weeks; afterwards, interferon was reduced to 3 megaunits up to 9 months. The percentage of sustained responses, transient responses and non responses were 18.5%, 24% and 57.4% in group A and 23.1%, 28.8% and 48.1% in group B (NS). The following factors were related to a poor response in the univariate analysis: an increase of serum iron levels, ferritin, Gamma-GT and bilirubin, anti-nuclear antibody positivity, presumed non-parenteral infection, an AST/ALT ratio greater than 0.75, a higher Knodell's index and a greater necrosis and fibrosis score. The multivariate analysis revealed that elevated serum iron and ferritin and anti-nuclear antibody positivity had an independent predictive value related to a non response. Our results appear to suggest that an induction with higher doses and the treatment over nine months are more efficient than the classic schedule. The prolongation of the induction period does not provide additional advantages.
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PMID:A comparison between two induction regimes for the interferon treatment of chronic hepatitis C. Response related factors. 914 98

Recurrence of hepatitis C is a significant problem after liver transplantation. This prospective study was done to assess the rate of recurrence and discuss two possible treatment modalities that have been successful in avoiding retransplantation. Twenty-one patients underwent orthotopic liver transplantation for hepatitis C at a metropolitan medical center over a 34-month period. The mean follow-up interval was 13.4 +/- 2.2 months (range 5-28 months). The patients were routinely evaluated with clinic visits and liver function tests, specifically total bilirubin, serum glutamic-oxaloacetic transaminase, and gamma-glutamyl transpeptidase. If values were elevated, the patient was admitted to the hospital for liver biopsy. Ten of the 21 patients demonstrated recurrence on biopsy. Two of 10 patients required no therapy. Interferon A was initiated in the remaining eight. Three of the eight patients had no significant response to interferon and were given intravenous ribavirin under an experimental protocol. Two of these three showed significant improvement in liver function values. The third died of chronic rejection. The incidence of recurrent hepatitis C after liver transplantation is significant. Many centers have had to resort to retransplantation. Our results show that with early detection and aggressive treatment with interferon and ribavirin, hepatitis C can be controlled and retransplantation may be avoided.
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PMID:Incidence and treatment of recurrent hepatitis C after liver transplantation. 915 27

Preliminary reports suggest that patients with interferon (IFN)-resistant chronic hepatitis C respond better to a combination of IFN-alpha and nonsteroidal anti-inflammatory drugs than to IFN alone. The efficacy of IFN combined with ketoprofen in the treatment of patients with IFN-resistant chronic hepatitis C was evaluated. Seventeen patients, nonresponsive after at least six months of treatment with IFN-alpha 2b and subsequently treated with the combination of IFN-alpha 2b plus ketoprofen for four months, were studied. Serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum hepatitis C virus (HCV) RNA were analyzed before and throughout treatment. No patient normalized serum aminotransferases after combination therapy. There were no significant differences in mean serum ALT and AST levels before and after ketoprofen intervention. Serum HCV RNA became undetectable after treatment in only one patient, but was detectable again three months after treatment cessation. These results provide no convincing evidence that the combination of IFN-alpha 2b with ketoprofen improves the response to IFN in patients nonresponsive to IFN alone.
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PMID:Failure of ketoprofen and interferon combination therapy to improve interferon-resistant chronic hepatitis C. 921 53


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