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)

We studied the relationships between the serum levels of viremia, aminotransferases and IgM anti-HBc, measured by monthly quantitative assays, in 52 untreated chronic hepatitis B patients (41 anti-HBe+, 11 HBeAg+) followed up for 12-20 months. Forty hepatitis exacerbations were observed in 17/41 anti-HBe+ (41.5%) and in 6/11 HBeAg+ patients (54.5%) (p = NS); all but one were clinically asymptomatic. We analyzed the fluctuations in the serum levels of the three parameters before, during and after the hepatitis exacerbations and found this chronological sequence of events in 96.2% of them: HBV-DNA increase-->ALT flare-->IgM anti-HBc increase. These results suggest that both antiviral immune reactions and ALT flares were triggered by quantitative variations in viremia. HBV-DNA baseline levels before flares were lower in anti-HBe+ (3.9 +/- 1.2 pg/ml) than in HBeAg+ patients (35.3 +/- 5.4 pg/ml) (p < 0.0001) and there was an inverse correlation between basal values and viremia level increases at the time of disease exacerbations (p < 0.001). This suggests that for a hepatitis exacerbation to occur, low basal viremia needed to increase markedly, while moderate increases in HBV-DNA serum levels were sufficient to trigger ALT flares in patients with elevated basal viremia. In conclusion, asymptomatic hepatitis B exacerbations are frequent in the natural history of chronic HBV infection, and monthly monitoring of HBV-DNA, ALT and IgM anti-HBc appears to be a suitable method to evaluate their frequencies and entities. This method can be a helpful guide for clinical and therapeutic decision-making in the single patient with chronic hepatitis B.
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PMID:Fluctuations in viremia, aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations. 796 77

The association between liver/kidney microsomal antibody type 1 and adult cases of hepatitis C virus-related chronic liver disease has been firmly established. In the presence of both markers, evidence of autoimmunity (liver/kidney microsomal antibody type 1) and actual viremia (serum HCV RNA), the therapeutic dilemma arises between steroids, which are beneficial to autoimmune but deleterious to viral diseases, and interferon-alpha, which may exacerbate an autoimmune disorder. Six patients with liver/kidney microsomal antibody type 1 and serum HCV RNA were given interferon-alpha: three showed a response pattern similar to that observed in autoantibody-negative chronic hepatitis C cases; the other three developed a sharp transaminase peak, which was not followed by HCV RNA clearance. Considering the brisk flare-up of liver cell necrosis, interferon-alpha treatment proved to be dangerous in the above three liver/kidney microsomal antibody type 1/HCV RNA positive cases. Subsequent steroid administration reduced alanine aminotransferase peaks, but may be harmful in viral infections. Therapeutic alternatives are needed: they will probably include pure antivirals (exerting no immunostimulatory effects) with or without immunosuppressive drugs.
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PMID:Interferon therapy in liver/kidney microsomal antibody type 1-positive patients with chronic hepatitis C. 798 9

The detection of serum HCV-RNA needs to be standardized. The aim of this study was to assess the effectiveness of the branched DNA amplification method in detecting and quantitating serum HCV-RNA in 54 blood donors, 33 with and 21 without increased serum alanine aminotransferase levels and with detectable serum HCV-RNA by polymerase chain reaction. HCV-RNA was detected by branched DNA signal amplification in 42/54 (77%) of the blood donors. Positivity rates were not different among the 21 blood donors with normal and the 33 blood donors with increased serum alanine aminotransferase levels (86% and 76%, respectively). Median serum HCV-RNA levels were not different among donors with or without increased serum alanine aminotransferase levels (28.6 x 10(5) Eq/ml and 14.7 x 10(5) Eq/ml, respectively). There was no significant correlation between serum alanine aminotransferase levels and serum HCV-RNA levels. These findings show that branched DNA signal amplification identifies most of the donors with true hepatitis C virus viremia and that the level of hepatitis C virus replication is not correlated to serum alanine aminotransferase levels.
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PMID:Detection and quantitation of serum HCV-RNA by branched DNA amplification in anti-HCV positive blood donors. 807 47

Antiviral treatment of chronic hepatitis C with interferon is reviewed. Alpha-interferon, both recombinant alpha-2a, -2b and human lymphoblastoid interferon given at a dose of > or = 3MU t.i.w. for 6-12 months will result in normalisation of ALT levels (complete response) in some 50-60% of treated patients with chronic hepatitis C virus (HCV) infection. Approximately half of the complete responders to interferon will relapse within 6 months once treatment is withdrawn (non-sustained response). Longer treatment schedules (6 vs. 12 months) seem to diminish the relapse rate and increase the percentage of sustained response. In patients with sustained response to interferon treatment with continuously normal ALT levels > or = 6 months after treatment stop a concomitant eradication of the viraemia is usually seen, whereas a non-sustained or non-response to interferon usually will indicate a continuous viraemia. Factors predictive of a favourable response are low pretreatment HCV RNA levels in serum, genotypes other than type II according to Okamoto, short disease duration, female gender and less pronounced liver damage, whereas high serum HCV RNA levels, having genotype II and cirrhosis, are predictive of a less favourable response. Patients with a sustained response and eradication of the viraemia will also improve their liver inflammation with diminishing scores for portal inflammation, piecemeal necrosis, lobular inflammation and also fibrosis after treatment. For non-responders and non-sustained responders to interferon, ribavirin especially in combination with interferon will offer some hope for the future.
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PMID:Interferon therapy in chronic hepatitis C virus infection. 808 99

Serial serum samples from 20 untreated patients with chronic hepatitis C virus (HCV) infection were tested for HCV RNA by a nested polymerase chain reaction assay using primers from the highly conserved 5' noncoding region to determine the relationship between hepatitis C viremia and the activity of liver disease during the natural course of chronic HCV infection. Semiquantitation of serum HCV RNA level was achieved by testing serial 10-fold dilutions of RNA extracts to determine the end-point titer. All the patients were HCV RNA positive at presentation. There was a poor correlation between the initial HCV RNA titer and serum transaminase levels. All patients except one were persistently HCV RNA positive during a follow-up period of 1.5-15 years, although 17 (85%) had periods of normal or near-normal transaminase levels. There was no correlation between changes in the serum transaminase levels and HCV RNA titer. Patients with chronic HCV infection have persistent viremia despite fluctuations in ALT levels.
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PMID:Longitudinal study of hepatitis C viremia in chronic hepatitis C. 810 70

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

The fate and significance of hepatitis C virus (HCV) infection after renal transplantation (TP) remain debated. We therefore evaluated the incidence and outcome of HCV infection in 120 kidney graft recipients both at the time of TP and 54 +/- 28 (13 to 123) months later using ELISA-II and RIBA-II immunoblot. Furthermore, the presence of anti-HCV antibodies at follow-up was correlated with HCV viremia, as detected by the nested polymerase chain reaction (PCR), and with chronically abnormal ALT levels. At the time of TP, 17 patients (14.2%) had anti-HCV antibodies. Compared to anti-HCV (-) patients, anti-HCV (+) patients had a longer duration of pre-TP dialysis (P < 0.001) and had received more pre-TP blood transfusions (P < 0.01). After an average follow-up of 48.5 +/- 24.7 (21 to 97) months, all these patients remained anti-HCV (+) but only 10 were still RIBA "reactive" due to the loss of reactivity against the 5-1-1, C100 and C33 (but not the C22) antigens. Five initially anti-HCV (-) patients had become (+) at follow-up. Among the 22 patients anti-HCV (+) at follow-up, 20 had HCV-RNA detectable by PCR but only 10 had elevated ALT. Ten out of 13 HBsAg (-) patients with elevated ALT were anti-HCV (+). Our study indicates that disappearance of ELISA-II anti-HCV antibodies is rare in kidney recipients and that HCV infection may also occur after TP. Anti-HCV antibodies are likely to reflect a persisting infection as suggested by the frequent detection of HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome of HCV infection after renal transplantation. 816 44

A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy.
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PMID:Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease. 819 99

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

Studies were undertaken to investigate whether interferon therapy could induce hepatitis C virus (HCV) carriage with normal serum alanine aminotransferase (ALT) values using an assay that combined reverse transcription and polymerase chain reaction. The subjects studied were 53 patients with chronic active hepatitis C who received interferon (alpha, 33 cases; beta, 20 cases) therapy. All were seropositive for HCV RNA prior to therapy. In all 22 complete responders, whose ALT levels fell to normal during therapy and for at least 24 weeks after therapy, HCV RNA became persistently negative except in two cases. The two had sustained viremia on treatment and for 1.0-1.5 years of follow-up, although their biochemical tests were normal. In 15 patients with a transient response in whom the disease recurred when interferon was stopped, HCV RNA was undetectable in 80% of the cases at the end of therapy, but the virus reappeared with subsequent elevation of ALT in all patients. However, 3 patients in this group had normal enzyme levels with viremia for 2.1-2.8 years of follow-up after acute deterioration of illness. In 16 patients who did not respond to interferon, HCV RNA was persistently positive during and after therapy. These findings suggest that interferon therapy induces a long-term carrier state of HCV infection with normal ALT levels in some patients.
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PMID:Long-term carriage of hepatitis C virus with normal aminotransferase after interferon treatment in patients with chronic hepatitis C. 822 41


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