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)

Antihepatitis C virus (HCV) IgM antibodies were found in patients with both acute and chronic hepatitis C. The aims of the study were to determine the significance, in terms of liver disease and virological parameters, of anti-HCV core IgM antibodies in the serum of patients with chronic hepatitis C, and the possible relationship between the presence of these antibodies before treatment and biochemical and virological responses to interferon therapy. Sixty-one patients with chronic hepatitis C were studied. Tests for serum anti-HCV core IgM antibodies were carried out before treatment. The patients received 3 mega units of interferon alpha-2a subcutaneously thrice weekly for at least 3 months (6 months when alanine aminotransferase activity was normal at month 3). A biochemical response to interferon therapy was defined as normal alanine aminotransferase activity at the end of treatment (month 6: biochemical response) and 6 months later (month 12: sustained biochemical response). A sustained virological response was defined as serum HCV RNA negativity by a polymerase chain reaction-based detection method (PCR) in patients with normal alanine aminotransferase at month 12. Anti-HCV core IgM antibodies were detected in 28 of the 61 patients (46%). The prevalence of these antibodies was significantly higher in patients infected with HCV genotype 1 (including subtypes 1a and 1b) than in patients infected with other genotypes (including 2a and 3a) (57% vs. 17%; P < 0.01). No significant difference was found between IgM-positive and IgM-negative patients as regards the mean age, sex ratio, serum alanine aminotransferase and gamma-glutamyl transpeptidase activities, the prevalence of cirrhosis in liver biopsy specimens, detection of HCV RNA by PCR, and quantitation by branched DNA assay. At month 6 of interferon therapy, normal alanine aminotransferase activity was significantly more frequent in IgM-negative than in IgM-positive patients (52% vs. 21%, respectively; P < 0.02). At month 12, normal alanine aminotransferase activity and PCR negativity were significantly more frequent in IgM-negative than in IgM-positive patients (18% vs. 0%, P < 0.04). It is concluded that anti-HCV core IgM antibodies in serum are significantly more frequent in patients infected by HCV type 1 than by other types. This suggests that their overall prevalence in patients with chronic hepatitis C in industrialized countries, where HCV type 1 accounts for the majority of infections, would be of the order of 50%, that anti-HCV core IgM antibodies are not associated with characteristic features of liver disease, and that their presence before treatment is associated with a failure of interferon alpha therapy to clear the virus.
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PMID:Significance of anti-hepatitis C virus core IgM antibodies in patients with chronic hepatitis C. 855 Dec 82

Paired serum and saliva specimens were collected on a regular basis from 18 asymptomatic blood donors participating in a controlled clinical trial of interferon alpha 2a (IFN) treatment of chronic hepatitis C virus (HCV) infection. Nine patients were randomised to receive interferon and nine to observation only. Serum and salivary HCV RNA was detected by a "nested" polymerase chain reaction (PCR) assay. Complete follow-up data were available for 14 patients (7 treated and 7 untreated). Serum ALT levels declined to normal in five of the seven IFN-treated patients by the twelfth week. Of these five, loss of hepatitis C viraemia was observed in three. Of the seven treated patients, the three responders had a lower viraemia level than the partial or nonresponders. Both nonresponders had infection with type 1 HCV, but the complete and partial responders were infected with types 2 or 3. HCV RNA was detected in the saliva of all seven observation patients during the follow-up period. HCV was also detected in the saliva of the two patients who did not respond to IFN treatment. No correlation was shown between the level of HCV RNA in serum and the presence of HCV RNA in saliva. A role for noninvasive salivary investigations in monitoring treatment is possible, but further refinement of the methodology is required.
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PMID:Serological and salivary markers compared with biochemical markers for monitoring interferon treatment for hepatitis C virus infection. 863 14

The treatment of hepatitis C virus (HCV) infections is essentially known for chronic hepatitis C and is mainly restricted to interferon alpha. Initial trials have indicated that around 50% of the patients with chronic hepatitis C respond to alpha interferon (administered at 3 MU, thrice weekly, during 6 months) by normalizing alanine aminotransferase at the end of therapy, although 25% were found to relapse after therapy. Normalization of biochemical tests is associated with an improvement in liver histological features and with decrease or loss of HCV from serum and liver. Response to therapy is influenced by both duration and dose levels of the treatment. Following studies which showed that higher doses and longer duration were more effective than the current recommendations of 3MU thrice weekly for 6 months have recently conducted to the recent recommendation of a 12 month course of therapy using 3 MU. The outcome of therapy was also shown to be negatively influenced by longer duration of disease and presence of cirrhosis. More recently, the critical role of virological markers has been emphasized with a lower rate of response in patients infected with the genotype 1 b and a high viral load. However, these factors do not certainly predict for an individual patient the quality of the response. Therapeutical goals are: to precisely define pre-treatment scores of response able to give each individual patient the optimal treatment regimen, non responders to interferon alpha and patients with a transient benefit of therapy. Thus, development of new treatments appears critical among which those with other interferons and above all the bitherapy using ribavirin and interferon alpha which may have a marked increase in efficacy in comparison with interferon alpha used as monotherapy.
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PMID:[Treatment of hepatitis C]. 874 94

Inflammation of the bile ducts was studied in liver biopsies from patients with chronic hepatitis C to determine whether the frequency of inflamed bile ducts changes with therapy and correlates with other histological variables and expression of class I and II MHC antigens on ductal epithelium. Twenty patients treated at UMMC between 1991 and 1994 underwent needle biopsies of the liver before and after therapy with interferon alpha 2B (IFN). A complete response to therapy was defined as a return to normal serum alanine aminotransferase levels occurring and persisting during therapy. The number of inflamed bile ducts/total ducts (%IBDs), presence of piecemeal necrosis and lymphoid aggregates, and grade of inflammation were assessed in each high-power field in all areas with bile ducts. The frequencies of these variables were compared in cirrhotics and non-cirrhotics and in patients with complete or incomplete responses to IFN. Frozen sections of biopsies from 5 patients were immunostained using antibodies to HLA-DR and B-2 microglobulin, and positive staining was noted on bile ducts. Before therapy, the %IBD was slightly greater in patients with cirrhosis. After IFN, both %IBD and serum alkaline phosphatase levels decreased in non-cirrhotics who responded to IFN. The change in frequency of IBD with IFN paralleled the changes in the other histological features. No correlation was noted between bile duct inflammation and expression of class I and II antigens. The conclusion is that inflammation of the bile ducts occurs frequently in chronic hepatitis C, correlates with other features of inflammation in the triads, and decreases in response to IFN therapy.
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PMID:Effect of interferon therapy on bile duct inflammation in hepatitis C. 876 34

Chronic hepatitis C is endemic among chronic haemodialysis patients. There have been a number of reports on hepatocellular carcinoma developing in such patients in Japan. The present study reports on the treatment of 15 patients who showed elevated ALT levels due to biopsy proven chronic hepatitis C with interferon alpha-2a (IFN). The dose schedule was 6 mega units (MU) daily for the first two weeks followed by 3 doses per week for 5.5 months. Side effects were so severe that IFN treatment was discontinued early in one patient, the dosage reduced in 11 and only tolerated in the original schedule by three patients. Excluding one patient who only recently completed the therapy, 13 were able to be evaluated for therapy efficacy by assessment of serum ALT and viral RNA. The overall results showed that IFN was effective in eight of 13 patients, a rate somewhat higher than the reported figures in this country. It is concluded that IFN therapy is indicated in haemodialysis patients with progressive chronic hepatitis C, but the dose administered should be lower and the dose schedule more flexible, perhaps 3 MU three times a week, in order to minimize untoward side effects.
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PMID:Interferon treatment for chronic hepatitis C in haemodialysis patients: suggestions based on a small series. 896 42

We report the case of a 51-year-old renal transplant patient, treated by interferon alpha (5MUI, three times a week) since he presented a coinfection by hepatitis B (HBV) and hepatitis C (HCV) virus for more than 7 years, associated with a chronic increase in serum alanine aminotransferase (ALT) levels and a chronic active hepatitis. The 4-month treatment was associated with a sustained normalization of ALT, a disappearance of HBV replication and a transient clearance of HCV viremia. Side effects were moderate and included thrombopenia (90,000/mm3), leucopenia (2200/mm3), an increase in serum creatinine (178 mumol/l). The withdrawal of alpha interferon was associated with the correction of these parameters. No rejection was observed on kidney biopsy. Meanwhile, liver histology was not affected by the treatment. To date, nineteen months after the end of alpha interferon therapy HBV DNA was still negative; ALT remained normal despite the early recurrence of HCV viremia; this emphasized the fact that HBV infection was certainly the most important factor involved in the patient's chronic hepatitis. It is concluded that alpha interferon therapy is able to decline HBV replication for a prolonged period in renal transplant patient although its use should be performed with caution due to the potential renal side effects.
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PMID:Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient. 900 30

There is limited information about the long-term efficacy of prolonged therapy (more than 6 months) with interferon alpha in hemophilic patients with chronic hepatitis C who are not coinfected with the human immunodeficiency virus (HIV-1). One hundred and seven hemophiliacs were randomly assigned to 3 million U of interferon alpha2b three times weekly for 12 months or no therapy. The patients were followed up for at least 12 months posttreatment. Response was assessed by both serial alanine aminotransferase (ALT) levels and hepatitis C virus (HCV)-RNA measured by reverse transcribed polymerase chain reaction (RT-PCR) method. Before treatment, serum levels of HCV-RNA were measured quantitatively by second-generation branched-DNA assay and the HCV genotype was determined by RT-PCR. Serum HGV-RNA, a marker of infection with the hepatitis G virus, was also measured by RT-PCR. Normalization of ALT was sustained and serum HCV-RNA was cleared in 6 of 45 treated patients, compared with none of the 50 untreated controls (13% v 0% P < .01). Low pretreatment viremia was the only feature that was associated with an increased likelihood of sustained response (P < .01). This study shows that multitransfused hemophiliacs with chronic hepatitis C not coinfected with HIV-1 respond at low rates to prolonged interferon therapy.
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PMID:A multicenter controlled, randomized, open trial of interferon alpha2b treatment of anti-human immunodeficiency virus-negative hemophilic patients with chronic hepatitis C. Hepatitis Study Group of the Association of Italian Hemophilia Centers. 942 35

Plasma vitronectin concentration was measured in 60 patients with chronic hepatitis C before and after interferon alpha treatment. The plasma pretreatment levels of vitronectin in the interferon non-responders was significantly lower than those in the interferon sustained and transient responders, but the levels were not different in the latter two groups. After interferon therapy, the plasma levels of vitronectin were significantly increased in all three groups, and they were correlated with the albumin levels. Absolute changes of plasma vitronectin before and after interferon treatment were significantly related to initial levels, but they were not related to those of albumin or alanine aminotransferase levels. The values of sensitivity and specificity for plasma vitronectin in the sustained responder and non-responder were 45% and 95% for each. These results suggest that chronic hepatitis C patients with low levels of plasma vitronectin may have a weak response in interferon therapy.
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PMID:Plasma vitronectin concentrations in patients with chronic hepatitis C treated with interferon alpha. 918 7

The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and sCD58) in human sera. Data concerning their role in chronic liver disease and their usefulness in disease monitoring are contradictory. We addressed the question whether elevated sCD54/sCD58 correlated either with disease activity or with decreased elimination secondary to reduced liver function in chronic hepatitis B. We studied 31 patients with chronic hepatitis B undergoing interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54 and sCD58 were measured at four weeks interval by specific Sandwich ELISA during a follow-up period of ten months. The maximal difference in concentration of each biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was determined for each patient during the whole follow-up period. These differences were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58) at the respective time points. Using this method, we were able to eliminate interindividual differences in serum concentrations for sCD54 and sCD58 and to avoid bias due to preselection of patients. We found that delta sCD54 correlated with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58 levels. Neither hepatitis B viremia nor the immune response to hepatitis B during the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58 levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings imply that sCD54 and sCD58 may be associated with a decrease in liver function that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful to monitor disease activity or response to interferon therapy in chronic hepatitis B. From our data we conclude, that decreased elimination of soluble adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible for increased serum concentrations detected.
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PMID:Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a longitudinal study in patients treated with interferon-alpha. 923 90

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.
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PMID:Long term recombinant interferon alpha treatment in MS with special emphasis to side effects. 934 19


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