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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serial serum samples and pretreatment and post-treatment liver tissue from patients with chronic hepatitis C virus (HCV) infection were tested for HCV RNA by reverse-transcription polymerase chain reaction and branched DNA signal amplification assays. At the end of treatment with interferon-alpha (IFN alpha), 4 of 5 patients showing no biochemical response (in alanine aminotransferase activity), 4 of 5 with transient responses, and 1 of 5 showing complete and sustained responses had HCV RNA detectable in serum. The corresponding numbers for liver tissue were 5, 5, and 0 (of 4). However, all 5 complete responders had virological relapses within 6 months. Biochemical response may not reflect virological profile during IFN alpha treatment of HCV.
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PMID:Discrepancy between biochemical and virological responses to interferon-alpha in chronic hepatitis C. 790 64

Longitudinal changes in lymphocyte subpopulations, including total and activated T cells, B cells, and NK cells as well as NK activity and 2',5'-oligoadenylate synthetase (2'5' AS) levels were determined in peripheral blood before, during, and after therapy with human recombinant interferon-alpha (HurIFN-alpha) in 39 patients with serologically and biopsy-confirmed chronic hepatitis C. Immunologic data obtained at baseline and during IFN-alpha administration were correlated with the clinical response to IFN-alpha therapy defined as a normalization of the serum alanine aminotransferase level. There were 23 responders (R) and 13 nonresponders (NR) to IFN-alpha and 3 patients were not evaluable. Prior to the use of IFN-alpha, the patients tended to have higher numbers of activated (DR+) T and NK cells but a lower number of CD3+CD25+ T cells than normal controls. During IFN-alpha therapy, highly significant induction of 2'5'AS was observed. The numbers of circulating WBC, total lymphocytes, and T and B cells were reduced during IFN-alpha therapy. In contrast, both the absolute number and percentage of activated CD3+CD25+ and CD4+DR+ T cells increased in response to the IFN-alpha therapy. The percentage of activated CD56+DR+ NK cells was also significantly elevated over the pretreatment baseline. IFN-alpha therapy had no effect on NK activity in peripheral blood mononuclear cells. No differences in the immunologic profile of R vs NR were noted, except that the number of IL2R+ T cells was increased transiently early during IFN-alpha therapy but only in the NR group. It was not possible to reliably discriminate between R vs NR to IFN-alpha therapy on the basis of longitudinal changes in the phenotype or function of immune effector cells.
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PMID:Effects of therapy with interferon-alpha on peripheral blood lymphocyte subsets and NK activity in patients with chronic hepatitis C. 795 64

The purpose of this study was to determine whether interferon-alfa (IFN-alpha) therapy benefits patients with transfusion-dependent thalassemia and chronic active hepatitis C, and whether their iron burden modifies the response to this therapy. We conducted a controlled trial of recombinant IFN-alpha (3 million units per square meter of body surface area, three times a week for 15 months) in 65 patients with thalassaemia major and chronic active hepatitis C; 14 of them were untreated control subjects. In 21 of the 51 treated patients, alanine aminotransferase values returned to normal within 6 months, and hepatitis C virus ribonucleic acid was no longer detected in serum; no changes were detected among control subjects. The response to IFN-alpha therapy was inversely related (p < 0.002) to the liver iron burden as assessed by atomic absorption, the histologic semiquantitative method, or both methods. During 3 years of follow-up, two responder patients had relapses. We conclude that IFN-alpha represents a useful therapeutic option for children with transfusion-dependent thalassemia and chronic active hepatitis C with a mild to moderate iron burden.
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PMID:Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C. 802 61

The patient was a 25-year-old male doctor, who had pricked his finger with a needle contaminated with blood from a 69-year-old male patient with liver cirrhosis (HCV-Ab positive, genotype II). He was informed from the blood bank that his blood was positive for anti-HCV and his GPT being 148 IU/l on the 65th day after exposure. He was admitted on February 16, 1993 and received a liver biopsy, which was consistent with acute viral hepatitis. His genotype was the same (type II) with the donor patient. IFN-alpha-2b of total doses of 656 Megaunits resolved the hepatitis completely and the HCV-RNA became negative as early as two weeks after starting IFN therapy. Liver biopsy after IFN therapy showed convalescence of acute hepatitis. The progression of acute hepatitis C to chronicity could be prevented by interferon therapy even in unfortunate cases of HCV transmission by needlestick. In conclusion, accidental needlestick should be followed for at least six months, and serum GPT and second-generation anti-HCV ELISA tests are recommended for all infected personnel.
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PMID:[A case of needlestick-induced acute type C hepatitis]. 805 46

The aim of this study was to compare the effects of two different therapeutical regimens of IFN alpha-2a in patients with HCV related chronic liver disease. Eighty one patients with HCV chronic hepatitis with or without cirrhosis entered the study; 42 and 39 patients were treated with 3 or 6 MU IFN, respectively. The results show that: 1) 25/39 (64.1%) patients treated with 6 MU and 21/42 (50.0%) patients treated with 3 MU had a complete response defined as a decline in serum ALT levels to the normal range during therapy; 2) complete response to 6 MU treatment was observed independently of the presence or absence of cirrhosis; in the 3 MU group, a complete response was observed in 31.6% of patients with CAH + cirrhosis as compared with 68.2% of those with CAH alone (p < 0.03); and 3) at 1 year after the end of the treatment we observed persistent ALT normalization in 40.6% and 28.2% of patients treated with 6 or 3 MU, respectively, and absence, of HCV viraemia (HCV-RNA) in 7/10 patients with CAH and in 2/7 patients with CAH + cirrhosis, mostly in patients treated with 6 MU. In conclusion, 6 MU IFN dose is more effective than 3 MU in reducing disease activity in HCV chronic hepatitis, specially in patients with CAH + cirrhosis.
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PMID:Recombinant human interferon alpha-2a therapy for chronic hepatitis C with or without cirrhosis: comparison of 3 or 6 MU for 1 year. 812 95

To compare the efficacy and tolerance of the simultaneous administration of levamisole plus IFN versus treatment with IFN alone in chronic hepatitis B, 39 patients were randomly assigned into two groups. Nineteen patients received 15 million units of recombinant alpha interferon 2b (rIFN-alpha 2b) 3 times a week for 4 months. The other 20 patients were treated with the same dose and schedule of rIFN-alpha 2b and 150 mg of levamisole simultaneously given during the first 6 weeks of treatment. At the end of the study (thirteenth month), serum HBV-DNA was negative in 59% of patients treated with interferon alone and in 37% of those treated with interferon and levamisole. HBeAg was negative in a similar percentage in the two groups (41% vs. 37%). Serum alanine aminotransferase levels decreased in patients who lost viral DNA. These data demonstrate that the combination of alpha interferon and levamisole, at the doses and under the schedule used in this study, does not achieve better results than the treatment with alpha interferon alone. Although tolerance to the simultaneous administration of alpha interferon and levamisole is good, secondary effects may be hazardous.
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PMID:Treatment of chronic hepatitis B with recombinant interferon alpha versus recombinant interferon alpha plus levamisole. 815 Nov 5

Hepatitis C virus (HCV) is an RNA virus that replicates in both the liver and lymphoid cells. Interferon-alpha (IFN-alpha) is a useful treatment of chronic hepatitis C (CHC) although resistance to this drug occurs frequently. The mechanisms underlying resistance to IFN remain unknown. In this work, we have measured the levels of glutathione in plasma and peripheral lymphoid cells from 15 healthy controls and 24 CHC patients, 10 of whom were without treatment and 14 showed high serum alanine aminotransferase (ALT) values despite therapy with lymphoblastoid IFN for more than 4 months. In all patients, glutathione levels in plasma and in mononuclear cells were depressed in comparison to controls. In IFN-unresponsive patients, the addition of 600 mg tid of oral N-acetyl cysteine (NAC), a glutathione precursor, resulted in a steady decrease of ALT values in all patients, with complete normalization in 41% of cases after 5-6 months of combined therapy. Administration of NAC alone for 1 month was without effect in the 10 patients that were not receiving IFN. Supplementation of IFN with NAC induced a near normalization of intralymphocytic glutathione, but plasma levels were only moderately increased. HCV replication was markedly inhibited in lymphocytes and viremia was cleared in one of the 8 patients tested. In conclusion, NAC enhances the response to IFN in CHC. Controlled studies are needed to ascertain whether antioxidant therapy might act in synergy with IFN in chronic viral hepatitis.
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PMID:N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. 822 88

The efficacy of r-interferon alpha 2a (IFM) versus acyclovir (ACV) and vitamin therapy in the treatment of herpes zoster is reported. A total of 305 patients were randomly divided into 3 groups. One million units of IFN were administered i.n. once a day for 6 days in 223 cases, oral ACV 200 mg five times daily for 7 days in 34 cases, and vitamin B12, B1 and B2 therapy at conventional doses for 7-14 days in 48 cases. The results showed that both IFN and ACV could reduce pain in patients with herpes zoster and cut the total duration of symptoms, in comparison with vitamin therapy (P < 0.01). In the IFN group, 45 patients (20.2%) experienced side effects, including mild fever in 35 cases (15.7%) and a slightly depressed leukocyte count or increased serum ALT level (3 cases each). In the ACV group, one complained of discomfort in the gastroenteric tract, and another patient reported lumbodynia.
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PMID:Treatment of herpes zoster: recombinant alpha-2a-interferon versus acyclovir and vitamin therapy. Clinical Study Group on Interferon. 827 20

We studied the effects of two different types of interferon alpha (natural interferon from human leukocytes vs. recombinant interferon 2b) in 64 patients with chronic Non-A, Non-B hepatitis; other finalities were: definition of the optimal duration of therapy with interferon alpha (IFN alpha), entity of side effects, cost-benefit ratio. Patients were randomly assigned to one of three groups, according to duration of IFN alpha treatment: Group I was treated for 12 months, Group II for six months, Group III for 3 months. Each group consisted of two subgroups, divided on the basis of the type of IFN used: subgroup A was administered natural IFN alpha, and subgroup B received recombinant IFN alpha 2b. Each patients was given 3 million units of IFN alpha by intramuscular injection on alternate days. At the end of treatment, a decrease in serum ALT activity was achieved in 39 cases (65%). The response rate was higher in Group I (89%) than in Group II (54%) and Group III (55%). Natural and recombinant IFN alpha 2b induced similar effects in patients treated for twelve months (Group I); recombinant IFN was more effective than natural IFN alpha in patients treated for six and three months. We conclude that the 12-month treatment with 3 million units of intramuscular recombinant IFN alpha, administered on alternate days, might be the optimal therapy schedule. This proposal is also supported by the evaluation of the cost benefit ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapy of chronic non-A, non-B hepatitis with alpha interferon. A comparison between natural and recombinant alpha interferon. 830 72

Forty-seven patients with chronic hepatitis C were treated with recombinant interferon alpha-2a (rIFN alpha 2a) given subcutaneously in a standard dose of 3 MU thrice weekly for 12 months. Stored baseline sera and monthly samples during treatment were assayed for anti-interferon neutralizing antibodies using the antiviral neutralization bioassay against 5 IU of rIFN alpha 2a. During therapy, 15 of 47 patients (31.9%) developed detectable levels of neutralizing antibodies within 2-8 months after starting treatment. After 12 months of therapy, 26 of 32 antibody-negative patients (81.3%) showed normalization or marked reduction of ALT levels compared to 4 of 15 (26.6%) who developed anti-IFN neutralizing antibodies (p = 0.0009). Four patients demonstrated antiviral response during treatment even in the presence of low levels or late occurrence of neutralizing antibodies. Six of the seven patients who had disease reactivation after an initial response developed high titers of neutralizing antibodies. Our results suggest that reactivation of chronic hepatitis C before completion of therapy seems to be an obvious consequence of anti-IFN neutralizing antibody formation.
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PMID:Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. 833 26


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