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)

Hepatitis C virus (HCV) genotype 4 is the principal HCV genotype found in Egypt and the Middle East. Little is known concerning its propensity to cause disease and the frequency with which infected individuals respond to interferon-alpha (IFN-alpha). We have investigated the response to treatment in a cohort of 100 chronic hepatitis C patients infected with genotype 4. All patients had biopsy-proven chronic active liver disease. Each was treated with 3 million units (MU) IFN-alpha, thrice weekly. Response was monitored, in 92 patients who completed treatment, by alanine aminotransferase (ALT) measurements and by polymerase chain reaction (PCR) for HCV. ALT levels remained abnormal in 64 patients during treatment (69.6%). Of the 28 patients who showed a biochemical response during treatment (30.4%), 18 maintained this over the 6-month posttreatment period. Amongst the sustained biochemical responders, HCV RNA was cleared from serum in only four of the 18 (22.2%) in this period. Histological improvement was observed in 26/51 (50.9%) of the patients who had a second biopsy. Hence, patients infected with HCV genotype 4 show a poor response to IFN-alpha therapy compared with genotypes 2 and 3, but a similar response to IFN-alpha compared with those infected with type 1b HCV. These findings have major implications for treatment strategies in the Middle East, including Egypt, where HCV genotype 4 is widely distributed.
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PMID:Response to interferon-alpha of Egyptian patients infected with hepatitis C virus genotype 4. 891 6

Interferon alpha (IFN-alpha) has been indicated to be dramatically effective in some but not all patients with chronic hepatitis C virus (HCV) infection. We investigated prospectively 27 patients of chronic hepatitis C, 12 females and 15 males, treated with IFN-alpha for a better regimen of the therapy and for any effective predictor of response to the treatment. All patients were treated with 3 to 6 million units (MU) of recombinant IFN-alpha 2b (n = 15) or lymphoblastoid IFN-alpha (n = 12) given 3 times weekly for 12 to 36 weeks. Patients with normal alanine aminotransferase (ALT) value during therapy, who sustained this response throughout 6 months follow-up after treatment was completed, were grouped into the complete responders. Patients with normal ALT value during therapy but who relapsed after treatment completed, were grouped as partial responders. Non-responders were defined as patients without normal ALT value during therapy. The rates of complete response, partial response, and non-response were 29.6%, 40.8%, and 29.6%, respectively. The degree of response to IFN-alpha therapy was not related to age, sex, type of IFN-alpha, history of blood transfusion, the state of liver pathology, or pretreatment level of ALT value. The complete responsive rate to IFN-alpha was higher in patients treated with total dose above 215 MU [38.1% (8/21) vs. 0% (0/6), p = 0.06], in patients treated for at least 24 weeks [40% (8/20) vs. 0% (0/7), p < 0.05], and in patients with non-genotype 1b/II HCV infection [40% (8/20) vs. 0% (0/7), p < 0.05]. We concluded that IFN-alpha was effective in the treatment of chronic HCV infection, particularly in those other than HCV genotype 1b/II. A high-dose, and long-duration regimen may be recommended for better response of chronic hepatitis C to IFN-alpha therapy.
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PMID:Treatment of chronic hepatitis C with interferon-alpha: a preliminary report. 891 79

We have evaluated the efficacy of treatment with recombinant Interferon-2b (IFN-2b) in 12 children with cancer who developed chronic hepatitis-B infection. Seven of them had lymphoblastic leukaemia and others had solid tumours. Seven cases were male. Mean age was 10.5 years with a range of 5-16 years. Chronic Hepatitis B was diagnosed biochemically, serologically and histopathologically. They were HBsAg(+), HBV-DNA(+), and HCV(-), HIV(-). Seven cases were HBeAg(+) and two of them were anti-Delta IgG(+). Liver biopsy revealed chronic active hepatitis in six cases and persistent hepatitis in three cases. IFN was given at the dose of 5 MU/m2 three times a week, subcutaneously for 6 months. It was well tolerated. After IFN therapy, ALT levels returned to normal in seven cases. All cases were still HBsAg(+). Four of them seroconverted to anti-HBe antibody. Loss of serum HBV-DNA in three cases, but 11 cases showed a marked decrease after IFN. The control liver biopsies showed that histopathological activity index was diminished in five cases. Other 16 patients, serving as control, received no therapy. Five of them were leukaemia and others were solid tumours. Twelve cases were male. Mean age was 9.3 years with a range of 4-19 years. After 6 months, only one patient lost HBV-DNA and three of them seroconverted to anti-HBe with normalization of ALT values. In our study, IFN treatment favourably influenced the progress of chronic hepatitis B in children with cancer.
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PMID:alpha-Interferon-2b treatment for chronic hepatitis-B infection in children with cancer. 893 55

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1-4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39 +/- 4 vs 3.6 +/- 8 Meq/ml, P < 0.0001) but significantly lower ALT (56 +/- 11 vs 97 +/- 12 units/liter, P = 0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.
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PMID:Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection. 894 74

Approximately 50% of patients with chronic hepatitis C respond to treatment with interferon-alpha. The aim of this randomized controlled trial was to evaluate whether an increase in dose of interferon-alpha augments response rate. One hundred thirty-eight patients with newly diagnosed chronic hepatitis C received a three-month course of 3 MU IFN-alpha2b administered every two days. All patients were anti-HCV and HCV-RNA (PCR) positive. Prior to treatment, a liver biopsy was performed. Complete response was defined by normal serum ALT concentrations and disappearance of HCV-RNA. After three months, 60 nonresponders were randomized (stratified according to histology) either to continue 3 MU interferon-alpha2b every two days for another six months (group A, total dose: 410 MU) or to receive increasing doses of interferon-alpha2b (6 MU every two days for three months, followed by 10 MU every two days for three months) (group B, total dose: 870 MU). Serum ALT concentrations were measured monthly and HCV-RNA at three-month intervals. Liver biopsy was repeated six months after end of treatment. Pretreatment characteristics of the randomized patients were: group A: N = 30; male/female: 20/10; age: 54 +/- 10 years; CPH 9, CAH 8, cirrhosis 13; mean ALT 108 +/- 98 units/liter; group B: N = 30; male/female: 21/9; age: 57 +/- 15 years; CPH 10, CAH 9, cirrhosis 11; mean ALT 90 +/- 40 units/liter. At the end of treatment six patients in group B but none in group A became responders [P = 0.011 (Fisher's exact test), intent-to-treat analysis]. All six responders were noncirrhotics. High-dose interferon was not tolerated by six patients in group B. Noncompliance resulted in five dropouts in group A and one in group B. During the six-month follow-up, four of the six responders relapsed. A patient in group A with increased serum ALT concentration but negative HCV-RNA at the end of treatment became a full responder after six months. Of nonresponders to 3 MU interferon alpha2b every two days for three months, 20% responded to higher interferon doses, but none to continued standard dose. Prolonged treatment with interferon may be necessary to obtain a sustained response. However, treatment with higher-dose interferon was not tolerated in 20% of the patients.
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PMID:Dose increase augments response rate to interferon-alpha in chronic hepatitis C. 901 66

The efficacy of various regimens using interferon-alpha (IFN-alpha) in the treatment of hepatitis C virus (HCV) infection was analyzed in a meta-analysis of 33 randomized clinical trials (RCTs). The results of the meta-analysis showed increased complete and sustained ALT response rates in patients receiving IFN 3 MU three times a week for six months compared with patients receiving placebo or no treatment. The dose effect (6 MU three times a week versus 3 MU three times a week) on complete ALT response rate at the end of treatment was significant, with a mean 10% improvement at both six and 12 months. There also was a significant dose effect on sustained response for 12 months treatment, with a mean 17% improvement. There was a significant treatment duration effect on sustained response rate at 3 MU three times a week and 6 MU three times a week, with a mean improvement of 16% (> or = 12 months vs six months) with 3 MU three times a week. Due to adverse events, we conclude that the best efficacy-risk ratio favors IFN treatment with 3 MU three times a week for at least 12 months. The results of our RCT comparing three IFN regimens showed that patients receiving 3 MU three times a week for up to 18 months exhibited significant improvements in histological activity score, normalization of serum ALT concentrations, and sustained response compared with patients receiving a lower dose or shorter duration of treatment with IFN. Together, these results support the conduct of another RCT to evaluate the hypothesis that long-term, continuous IFN treatment may significantly reduce the incidence of cirrhosis in patients with HCV infection.
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PMID:Treatment of chronic hepatitis C by interferon for longer duration than six months. 901 84

Clinical features of HGV infection as a novel virus infection have not yet been clarified enough. We studied the implication of HGV in the activity of hepatitis and the sensitivity of HGV to IFN. We treated 10 HGV RNA positive patients with chronic hepatitis C with IFN. HGV RNA was identified in serum by RT-PCR method using the primer derived from the base sequences of the NS5 region of HGV genome. HGV RNA became negative in the all of 10 patients during IFN treatment, but returned to be positive again in the all patients after the completion of IFN treatment. In 5 of 10 patients, HCV RNA became persistently negative. In 3 of these 5 patients, ALT was continuously normal and hepatitis subsided biochemically and clinically after IFN treatment. We assume that HGV is sensitive to IFN, but could not be implicated in hepatitis or liver damage.
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PMID:[Interferon treatment for hepatitis G virus infection in patients with chronic hepatitis C]. 908 71

In 72 chronic hepatitis C patients treated with IFN, liver biopsies were performed before and after IFN treatment, and histological changes were examined. In complete responders, the grading score improved significantly since 6-mo after IFN treatment, and the staging score improved significantly since 12-mo after IFN treatment. In long-term responders underwent a following liver biopsy 4-5 yr after IFN treatments; 5 had normal liver histology. In partial responders, both the grading and staging score did not improve significantly. But, in the cases who had sustained normalization of ALT levels after IFN treatment, both the grading and staging score improved after treatment. In non-responders, both the grading and staging score did not improve significantly.
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PMID:[A long-term histological prognosis after IFN therapy for chronic hepatitis C]. 909 34

We previously reported that interferon-gamma (IFN-gamma) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229 +/- 119 pg/ml, P < 0.01) and liver cirrhosis (LC) (185 +/- 88 pg/ml, P < 0.05) than in controls (119 +/- 27 pg/ml), while it was decreased during IFN treatment (70 +/- 25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-gamma production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-gamma production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-gamma production by some cells.
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PMID:Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection. 909 22

Chronic active hepatitis due to HCV represents a severe progressive disorder of the liver, At present, Interferon seems to be the most efficacious treatment available, however, only 20-25% of the patients treated achieve complete remission. The efficacy has, therefore, been evaluated of Ribavirin, a nucleoside analogue active both on DNA and RNA viruses, in the treatment of non responders to a previous course of interferon. Twenty patients were randomly assigned to two groups: A) received the association R (800 mg/day for 2 months)+interferon (9 Mu/week for 6 months); B) received IFN (9 Mu/week for 6 months). All patients completed the study without important side effects. Four patients in group A presented reduced ALT and loss of viraemia during treatment with Ribavirin. Only one patient in group B had reduced indices of cell lysis and was negative for HCV-RNA during the course of the study. However, viremia and an increase of ALT values were observed in all of these subjects once treatment was interrupted. The results emerging from this study indicate that Ribavirin therapy, at the dose and duration of treatment employed, is not sufficient to change the natural course of events of chronic active hepatitis from HCV.
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PMID:Pilot study of a short course of ribavirin and alpha interferon in the treatment of chronic active hepatitis C not responding to alpha-interferon alone. 913 95


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