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)

Interferon is being used for therapy of chronic hepatitis C, but its long-term results have not been reported. We studied 65 patients with this disease who were monitored for at least 2 years after completion of the therapy. Almost all patients who had responded to therapy at 6 months after the end of therapy had normal levels of alanine aminotransferase (ALT) when evaluated later. The level of ALT became normal for the first time in some patients more than 6 months after therapy ended. The level of ALT in many of the patients without HCV RNA had become normal 6 months after the end of the therapy. One of three schedules was employed: three times weekly long-term; daily for two weeks and none for two weeks in a cycle; and daily for several weeks; 57%, 29%, and 17% of the patients on these schedules came to have normal ALT levels. Patients without HCV RNA at six months after completion of therapy tended to have higher responses in terms an increased level of 2',5'-oligoadenylate synthetase of mononuclear cells in vitro before therapy began. However, therapy three times per week was effective even for some patients judged not responsive to IFN by this test. The results showed that IFN therapy was effective for chronic hepatitis C when judged by long-term results.
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PMID:Long-term therapeutic efficacy of interferon for patients with chronic hepatitis C. 835 19

Interferon-alpha (IFN-alpha) has proven useful in the treatment of chronic hepatitis C, but a relapse in response is frequently observed. The possible benefit of daily administration of recombinant IFN-alpha 2A at an escalating (from 1.5 to 9 MU) regime depending on the evolution of serum aminotransferase (ALT) levels was evaluated in 31 adult patients with chronic hepatitis C. At the end of the first month with 1.5 MU of rIFN-alpha 2A, 9/31 (29%) had normal ALT values. Then, 22 patients were given 3 MU daily and at the second month 4 patients (18%) normalized ALT values. The 18 non-responders received 6 MU and 4 of them (22%) normalized ALT values (1 patient dropped out). Finally, the remaining 13 non-responders were given 9 MU and in 4 (30%) ALT fell to normal ranges. Three non-responders to 1.5 MU normalized ALT values when the dose of rIFN-alpha 2A was increased (n = 2, 3 MU; n = 1, 9 MU). The overall response achieved was 68%. Within 3 months after cessation of treatment, 12/20 (60%) responder patients had a relapse in ALT levels. Therefore, although daily administration of rIFN-alpha 2A does not improve the results obtained with a thrice-weekly schedule, a proportion of non-responders could benefit from an escalating dose to a high amount (63 MU/week) of rIFN-alpha 2A.
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PMID:An escalating dose regime of recombinant interferon-alpha 2A in the treatment of chronic hepatitis C. 844 28

Based on results from extensive clinical research, interferon-alpha-2a (IFN-alpha-2a, Roferon-A, F. Hoffmann-LaRoche Ltd., Switzerland) and other interferons have been registered for the treatment of chronic active hepatitis B. The officially recommended dose regimen is 4.5 MIU (or 2.5 MIU/m2) thrice weekly for 6 months. To present guidelines for the optimization of treatment for individual patients, 3 major controlled trials from our worldwide research program with a total of 416 patients were reviewed in a meta-analysis. Before deciding whether to treat or not, the history, prognosis and chances of treatment success for a given patient must be carefully assessed. Liver histology and repeated quantitative measurements of markers for viral replication (HBV-DNA, HBeAg) and biochemical markers for liver disease such as ALT are valuable indicators. After the decision to treat, monthly quantitative measurements of these markers make it possible to monitor therapeutic success. Depending on the course they run, treatment can continue unchanged, be adjusted in dose or duration until a full response is achieved, or be terminated early in case of evidence of non-response.
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PMID:To treat or not to treat? The judicious use of interferon-alpha-2a for the treatment of chronic hepatitis B. 850 38

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant recipients. To assess the efficacy and the safety of therapy with interferon alpha (IFN alpha) in such a population we conducted a prospective study where 16 kidney transplant recipients with chronic hepatitis C received recombinant IFN alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All the patients had stable renal function for at least 1 year (mean serum creatinine 125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the beginning of the study. In 15 patients serum alanine aminotransferase (ALT) levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P = 0.0044). ALT remained in the normal range as long as IFN alpha was continued. Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to 88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end of IFN alpha therapy remained positive in all the patients who scored positive at the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight loss) were frequent leading to four patients dropping out of the study. The haematological tolerance was moderate. The major concern was the increase in serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only six patients experienced renal failure occurring 45-168 days after the beginning of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered interstitial inflammatory cellular infiltration and moderate mesangial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preliminary results of treatment of chronic hepatitis C with recombinant interferon alpha in renal transplant patients. 852 7

The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. A follow-up of 6 months or more after interferon-alpha was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%); II. Normalization followed by persistent relapse after IFN = 7 (15.9%); III. Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclusion, ALT patterns vary widely during and after IFN treatment and can be classified in at least 6 types.
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PMID:Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. 852 70

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

We investigated the spontaneous and phytohemagglutinin-stimulated production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) by peripheral blood mononuclear cells in patients with chronic hepatitis C during treatment with interferon-alpha (IFN-alpha). Spontaneous productions of these were significantly higher in patients with chronic hepatitis C than in healthy subjects. For patients prescribed interferon, stimulated production of TNF-alpha was significantly higher in complete responders than in partial responders, but the differences were small between the other cytokine levels and outcome of IFN treatment. Spontaneous production of these cytokines was higher in patients with genotype III with complete response than in genotype III patients with a partial response, but this was not the case in patients with genotype II. There was a negative correlation between these cytokines and histological activity index. Spontaneous production of cytokines was decreased only in complete responders after the administration of interferon. These data suggest that the elevated production of cytokines in patients with chronic hepatitis C may be due to host response to the virus, and monitoring cytokines along with alanine aminotransferase and hepatitis C virus RNA during treatment may provide more precise information of the effectiveness of therapy.
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PMID:IL-1 beta and TNF-alpha produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C. 860 75

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.
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PMID:Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus. 867 62

Nine children suffering from chronic hepatitis due to hepatitis B virus (HBV) infection were treated with recombinant IFN-alpha-2C for 16 weeks. Replication of HBV was inhibited in 5 cases while a decreased inflammatory process in the liver was attained in 3. The treatment was very well tolerated in all of the studied children. A significant increase of ALT activity in the fourth week of treatment seems to be a positive prognostic factor.
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PMID:[Interferon alpha in the treatment of chronic hepatitis B in children]. 869 95


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