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:2.3.1.109 (AST)
6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred patients with severe Chronic C Hepatitis, > 60 years of age and a life expectancy > 10 yrs were randomised to receive a course of lymphoblastoid a-IFN or a non specific support therapy as control. Patients randomised to IFN (no. 50) were treated with 3MU i.m. every two days for 2 months and then with 6MU i.m. every second two days for additional 10 months. All patients were followed-up for 12 months at the end of treatment. At the end of treatment, 30/50 patients in the IFN group showed a complete remission with normalisation of ALT and AST values (60%). Partial remission occurred in 11 patients (22%) whose transaminase values improved but did not normalise. No response was seen in 9 cases (18%) who showed similar pre- and post- treatment transaminase levels. On the contrary, normalisation of ALT-AST was observed in just two patients assigned to the non-specific therapy, whereas pre- and post-treatment values were similar in the remaining 48 patients. In patients receiving IFN a marked histological improvement was observed at the end of therapy in 22 responders (73.3%) and in 6 partial or non responders (30%) treated with IFN. No histological improvement was observed in control patients. At the end of the 12-month follow-up (24 months from the beginning of the study), 12 responders relapsed (40%) showing levels of transaminase which returned to the pre-treatment values within the second month from the IFN discontinuation. Therefore 18 out of 50 patients (36%) showed a long-term response to lymphoblastoid interferon. Lymphoblastoid a-IFN is an effective and safe therapy in elderly patients whose life expectancy justify its use and generates responses which are similar to those observed in younger subjects.
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PMID:Treatment of chronic hepatitis C with lymphoblastoid interferon alpha in elderly patients. 944 98

Medical guidelines for interferon-alpha2a or -alpha2b (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection depend upon baseline liver histology. A better long-term response to IFN-alpha therapy correlates with less inflammation and absence of cirrhosis. It has been suggested that the presence of cirrhosis in patients with chronic hepatitis C virus infection may be predicted based on an AST/ALT ratio > or = 1. This study was designed to determine if the presence of cirrhosis can be predicted in patients with chronic HCV infection by such a ratio. Seventy-seven patients, including 23 cirrhotics, with chronic HCV infection were studied. Serum ALT, AST, and HCV-RNA levels and hepatic activity index (HAI), reflecting histologic inflammation in all liver biopsies, were assessed. AST/ALT ratios and mean ALT, AST, and HCV-RNA were determined for both cirrhotic and noncirrhotic patients. HAI was correlated with ALT, AST, and HCV-RNA levels, the latter determined by quantitative RT-PCR. The likelihood ratio (LR) and positive predictive value of an AST/ALT ratio > or = 1 for cirrhosis was 7.3 and only 77%, respectively. In cirrhotics vs noncirrhotics, there were no significant differences between mean serum ALT (149 +/- 28 vs 176 +/- 17 units/liter), AST (139 +/- 28 vs 102 +/- 8 units/liter), or HCV-RNA levels (589,160 +/- 147,053 vs 543,915 +/- 75,497 copies/ml), respectively. There was a significant, but clinically weak, correlation between serum ALT and HAI (r = 0.234), and none between HAI and either serum AST or HCV-RNA levels. Our results support the need for a liver biopsy prior to treatment of chronic HCV infection, since the AST/ALT ratio fails to predict accurately the presence of cirrhosis.
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PMID:AST/ALT ratio > or = 1 is not diagnostic of cirrhosis in patients with chronic hepatitis C. 975 86

The study aimed to evaluate the behavior of alpha-glutathione S-transferase (alpha-GST) in the serum of hemodialysis patients with hepatitis C virus (HCV) infection following treatment with high-dose IFN-alpha-2b. Ten patients with detected anti-HCV antibodies and HCV RNA by RT-PCR were selected and treated with high-dose interferon (IFN)-alpha-2b, 10 million units s.c. daily for 2 weeks followed by 3 times per week for 6 additional weeks. Blood samples were obtained from these patients at baseline for plasma alpha-GST and hepatic aminotransferases. Patients were monitored with weekly blood counts and monthly liver enzymes. Biochemical (normal alpha-GST and ALT) and virologic (negative HCV RNA by RT-PCR) responses were observed in 3 (30%) of the 10 patients. At the end of the follow-up (follow-up duration 44 weeks), 3 patients demonstrated long-term biological and virologic responses and 7 had relapses. In the nonresponders plasma AST and ALT approached normal levels on some occasions despite persistent viral RNA. In contrast to transaminases alpha-GST remained distinctly elevated in nonresponders and provided a more clear distinction between the responders and nonresponders. In conclusion, plasma alpha-GST, as a sensitive and reliable marker of response, may have a role in the monitoring of hemodialyzed patients undergoing IFN-alpha-2b therapy.
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PMID:The role of alpha-glutathione S-transferase in the monitoring of hemodialysis patients with hepatitis C virus infection undergoing high-dose interferon-alpha-2b therapy. 1022 80

Hepatitis C envelope proteins (E1, E2) induce protective neutralizing antibodies. The extent of sequence diversity reflects the host's ability to control viral populations and the response to antiviral therapy. Attempts to prepare effective vaccines against HCV are foiled by lack of prolonged protective immunity. Plasmid vaccines and the use of uninfectious virus-like particles are being developed. HCV induces a cellular humoral immune response, but this is inadequate to clear the virus and the disease becomes chronic. In any patient, the natural history of HCV infection depends on the age when infected, and the presence of other diseases. The transfusion-related disease has a worse prognosis than that transmitted by syringes and needles. The outlook in 'healthy blood donors' is uncertain. Interferon therapy for 3 or preferably 6 months results in a sustained response in about 30% of patients. Negative serum HCV RNA and normal AST values after 3 months of therapy indicates that there may be a sustained response. Whether or not to stop treatment at that time if HCV is still positive remains a matter of debate. The role of interferon treatment in preventing progression to cirrhosis and hepatocellular cancer is still uncertain. Ribavirin therapy alone reduces transaminases and hepatic histology improves. Improved results follow the combination of ribavirin with interferon. Ribavirin may have immuno-modularity and anti-inflammatory actions. Hepatitis G virus (HGV) is unlikely to play a significant role in liver disease in man.
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PMID:The hepatic flaviviridae: summary. 1076 28

An 11-year-old boy was diagnosed as having acute lymphoblastic leukemia (ALL, L1) in 1987 and underwent treatment with an ALL high-risk protocol (prednisolone, vincristine (VCR), daunorubicin, 1-asparaginase), which resulted in complete remission. In 1990 he developed chronic hepatitis C and received interferon therapy. In December 1994, ALL recurred, and the patient was treated with VCR. He subsequently developed severe hemolysis (Hb 12.5 g/dl-->6.8 g/dl) with increases of indirect bilirubin, AST, and LDH. Furthermore, symptoms resembling a syndrome of inappropriate secretion of ADH (SIADH) and DIC developed. Upon incubation of the patient's red blood cells with VCR in vitro, extreme deformity of the cells was observed. These findings suggested that splenomegaly, due to liver cirrhosis which had developed rapidly from chronic hepatitis C while the patient was in an immunosuppressed state induced by anticancer drugs, had trapped the deformed red blood cells and resulted in severe hemolysis. The patient died on the 165th day after admission due to liver failure.
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PMID:[Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis]. 1119 45

The purpose of this study was to evaluate caffeine clearance, a quantitative measurement of metabolizing capacity of the liver, in chronic hepatitis B and C before and after interferon treatment. Biochemical test using AST and ALT, virological test, and caffeine clearance were measured in eighteen patients with chronic hepatitis B and five patients with chronic hepatitis C at pre and post treatment with interferon. Caffeine clearance was determined in each patient using two point analysis following a 3.5 mg/kg oral administration of caffeine solution. Blood samples were subsequently collected at 12 and 16 hours after caffeine administration and assayed for serum caffeine level by HPLC technique. Clearance was calculated using the equation of Cl = Kel x Vd. It was found that caffeine clearances determined before and after interferon treatment were not significantly different in both chronic hepatitis B and C inspite of biochemical and virological responses after therapy. Caffeine clearance change in two diffferent groups of chronic hepatitis B defined as biochemical response and nonresponse were compared. Although caffeine clearance change between responders and nonresponders to interferon treatment was not significantly different, it tended to increase in those patients who had biochemical response to interferon. It appeared that metabolic capacity of the liver does not change with interferon therapy inspite of biochemical and virological responses.
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PMID:Caffeine clearance in patients with chronic viral hepatitis: before and after interferon therapy. 1152 34

Fifteen male patients with acute hepatitis C aged 16-44 years were treated with neovir, an interferon inducer, administered intramuscularly in a daily dose of 250 mg 2-3 times a week for 3 months. By the end of this therapy the RNA of hepatitis C virus could still be detected in 84.6% of the patients, the characteristics of ALT, AST and alkaline phosphatase exceeded the norm more than twofold. The results of neovir therapy are regarded as ineffective.
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PMID:[Effect of neovir in the treatment of acute hepatitis C]. 1155 May 70

Polymyositis is a rare complication of interferon alpha treatment as a result of immune-modulating role of the drug itself. In this case, interferon alpha induced polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with history of chronic hepatitis B. To treat hepatitis B, interferon alpha was administered until the proximal muscle weakness developed. Thereafter, sixteen cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were instituted and led to an improvement in subjective symptoms with decreases in level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite of the cessation of interferon treatment. Unlike the persistently elevated serum HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case shows that clinical symptoms of polymyositis improved with steroid and immunoglobulin treatment without deterioration of the hepatitis B. To our knowledge, this is the first case of polymyositis associated with dilated cardiomyopathy after the administration of interferon in a patient with hepatitis B.
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PMID:A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. 1185 Jun 6

The possibility of assessing the relationship of ultrasound (US)-detected abdominal lymphadenopathy with etiology, biochemical findings, and histologic data in patients with chronic liver disease was evaluated. US examination of the upper abdomen was performed in 321 consecutive patients with various chronic liver disorders and 56 control patients. The prevalence of lymphadenopathy in chronic liver disease was 38%. This prevalence varied according to etiology of liver disease, from 50% in chronic hepatitis C virus (HCV) to less than 10% in alcoholic cirrhosis and hepatitis B-virus (HBV)-related chronic liver disease. Patients with lymphadenopathy showed significantly higher serum levels of AST and ALT, as well as greater histopathological severity on liver biopsy specimens. In anti-HCV positive patients, there were no differences in the prevalence of lymphadenopathy according to HCV genotypes, whereas lymphadenopathy occurred less frequently in responders to interferon therapy than in nonresponders.
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PMID:Clinical significance of abdominal lymphadenopathy in chronic liver disease. 1197 9

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.
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PMID:Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection. 1199 75


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