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)

To evaluate the prevalence and duration of viremia in relation to the features of liver disease, we investigated hepatitis B virus (HBV) DNA by the polymerase chain reaction in the serum of 39 children with chronic hepatitis B, after hepatitis B e antigen to antibody seroconversion. During a mean observation period of 8.2 +/- 3.8 years after seroconversion, all patients were asymptomatic; 36 had persistently normal alanine aminotransferase levels, and three had occasional mild alterations. Liver histology, checked in 21 patients, showed persistent hepatitis in nine, fibrosis in 10, and cirrhosis in two cases. HBV DNA was always undetectable by dot blot hybridization. Five children eventually cleared hepatitis B surface antigen, including one with cirrhosis who developed liver cancer at 19 years. HBV DNA was detected by polymerase chain reaction in 87% of children within 5 years of follow-up, in 58% of cases 6-10 years after seroconversion (p < 0.001), and in 50% of patients investigated later. Long-term viremia was found in two patients (40%) who cleared HBsAg, including the one who developed liver cancer. The chances of clearing viremia during follow-up were higher in children with acute hepatitis at the onset of illness (86%) than in those with asymptomatic onset (37%; p < 0.05). Our results show that low levels of HBV viremia, probably reflecting low levels of virus replication, persist for several years in children with chronic hepatitis B after hepatitis B e antigen to antibody seroconversion and remission of liver disease, even after the clearance of hepatitis B surface antigen. Persistent replication could support mild biochemical alterations and inflammatory liver lesions. It could allow late reactivation of liver disease and may play a role in the development of carcinoma.
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PMID:Long-term persistence of hepatitis B virus DNA in the serum of children with chronic hepatitis B after hepatitis B e antigen to antibody seroconversion. 870 80

The loss of haemolytic activity in sera during storage at low temperature (the cold activation of complement) was observed in 136 of 184 (74%) patients with chronic liver disease associated with hepatitis C virus (HCV) infection. This was more frequent than observed in the three of 40 (8%) patients with chronic hepatitis B (P < 0.001) or none in 43 normal controls (P < 0.001). Of 103 patients with chronic hepatitis C who had completed a full course of recombinant interferon-alpha 2a therapy (total dose: 516 x 10(6) U), 40 responded completely and 21 responded partially, as judged by the normalization or decrease of alanine aminotransferase levels 6 months after the completion of therapy; 42 patients did not respond at all. The cold activation of complement persisted in five (13%) complete responders, less often than in 33 (79%) non-responders (P < 0.001). At the completion of interferon therapy, the cold activation of complement persisted in 12 of 54 patients despite the normalization of alanine aminotransferase. Spontaneous exacerbation of hepatitis occurred in seven of 12 (58%) patients with cold activation, which was more frequent than in the four of 42 patients (10%) without it (P < 0.01). The cold activation of complement disappeared along with the loss of HCV-RNA in five of six responders during the 6 month period after the completion of interferon therapy, while both cold activation and HCV-RNA persisted in all eight non-responders. These results indicate that the cold activation of complement may be useful as a marker of HCV viraemia for monitoring the response to interferon in patients with HCV infection.
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PMID:Cold activation of complement in sera from patients with persistent hepatitis C virus infection on interferon therapy. 871

To study the incidence and outcome of GB virus C (GBV-C) infection in blood recipients. Serum samples collected in a prospective study were examined for GBV-C RNA by a nested polymerase chain reaction assay. Among the 400 adults who underwent cardiac surgery, 40 were positive for GBV-C RNA, including six whose pretransfusion sera were already positive and seven coinfected with hepatitis C virus (HCV) during transfusion. The risk of transmission was estimated to be approximately 0.46% per donor. GBV-C viremia was detectable 1 week after transfusion and could persist for 8 years. However, no evident symptoms or signs were noted in the 25 patients infected by GBV-C alone, and the average peak serum alanine aminotransferase activity was 31 IU/L only (range, 12 to 123), with persistently normal levels in 20 patients. In the seven patients coinfected with HCV, the clinical courses of posttransfusion hepatitis were similar to those infected by HCV alone. In eight patients with posttransfusion non-A approximately E hepatitis, only one was positive for GBV-C RNA. Sixty samples were chosen to test hepatitis G virus (HGV) sequences, 26 of the 30 GBV-C positives were positive for HGV RNA in contrast to none of the 30 GBV-C negative samples. In conclusion, GBV-C can be transmitted by transfusion in approximately 9% of patients who underwent cardiac surgery. Nevertheless, this virus does not seem to cause classic hepatitis in most instances.
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PMID:A prospective study of transfusion-transmitted GB virus C infection: similar frequency but different clinical presentation compared with hepatitis C virus. 878 48

Thirty-six patients with hepatitis C virus-RNA positive chronic hepatitis were studied to evaluate whether recombinant alpha-2b interferon, in medium-high doses, (6-9 MU 3 times/week) over a long period (12-18 months), was more effective in reducing or normalizing alanine aminotransferase values, and in reducing the relapsing percentage than the historical trials. At the end of the 12th and 18th month of treatment, mean alanine aminotransferase values were significantly reduced; the level of complete responses was 36.1%, at the end of the 12th month, and 19.4% at the end of the 18th month (intention to treat). These results were no better than comparable findings in the literature. At the end of the first follow-up (12th month), percent complete responses fell to 15.5%, with a relapse rate of 14.3%. At the end of the second follow-up (24th month), percent complete responses fell further to 11.1% (all 4 patients with a 24 months sustained response showed absence of viraemia), with a relapse rate of 42.9%; even these percentages were judged unsatisfactory. In conclusion, no significant advantage was obtained by prolonging interferon treatment and/or using higher dosages. However, the possible virus clearance in all the long-term responders seems to justify further investigation in terms of cost-benefit analysis.
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PMID:Prolonged treatment of chronic C hepatitis by means of medium-high doses of recombinant alpha-2b interferon: an open study to evaluate response and long-term relapse. 878 22

The natural course of non-A, non-B (type C) hepatitis was studied in 62 haemodialysis patients. From the onset of the disease, serum alanine aminotransferase levels were monitored monthly for 9-218 mon (median 115). After fluctuation of aminotransferase levels for 1-206 mon (median 39), 57 (92%) patients showed normalization of these levels lasting until the end of the follow-up, which was for > 2 yr in 31 (50%) cases and for > 5 yr in 15 (24%) cases. At the end of follow-up, hepatitis C viraemia was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and branched DNA (bDNA) assay. Viraemic levels were significantly lower in the 15 patients with normal aminotransferase for > 5 yr (median RT-PCR + ve/bDNA-ve, range RT-PCR-ve to 10(6.7) Eq/mL) than in the 47 cases with normal levels for < 5 yr (median 10(6.6), range RT-PCR + ve/bDNA-ve to 10(7.6) Eq/mL) (P < 0.01). Moreover, a significant inverse relation was observed between viraemic levels and the duration of aminotransferase normalization (r = -0.46, P < 0.01). These findings indicate that biochemical remission of hepatitis C may be frequent in haemodialysis patients and may be related to viral attenuation.
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PMID:Hepatitis C biochemical remission and viral replication in haemodialysis patients. 880 Dec 84

To determine the clinical significance of viral quasispecies heterogeneity, 59 patients with chronic hepatitis C were studied using singlestranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1); of these, 48 were subsequently treated with interferon-alpha. The SSCP method was validated using clones of known nucleotide sequence. HVR1 was amplified in 54 of 59 (92%) patients. The median number of SSCP bands per sample was 6 (range: 2-12). Increased quasispecies heterogeneity correlated with the estimated duration of HCV infection (P < 0.05), parenteral-acquired HCV infection (vs. sporadic, P < 0.05), serum HCV RNA levels (P < 0.05), and HCV genotype 1 infection (P < 0.05), but not with age, serum AST, ALT, or Knodell score. Patients who had complete and sustained response to interferon-alpha (n = 11) had lower pre-treatment quasispecies heterogeneity compared to patients who had complete response with relapse (n = 18, P < 0.05) or no complete response (n = 16, P < 0.01). However, multivariate analysis revealed that HCV viremia was a stronger predictor of response to interferon-alpha. These findings indicate that the estimated duration of HCV carriage, serum HCV RNA levels, and HCV type 1 are important determinants for the evolution of HCV quasispecies heterogeneity; and that increased HCV quasispecies heterogeneity is another marker associated with a poor subsequent response to interferon-alpha.
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PMID:Clinical implications of viral quasispecies heterogeneity in chronic hepatitis C. 881 72

The clinical importance of hepatitis B virus (HBV) genome variability has been reported recently. One example is the occurrence of hepatitis B virus pre-core mutants, which arise during spontaneous or interferon-induced seroconversion from HBeAg to anti-HBe and are thought to be selected by immune pressure. A survey of HBV pre-core mutants and viral genotypes in 35 HBeAg negative patients during interferon therapy was carried out to understand viral pathogenesis in this form of chronic hepatitis B. Seventeen patients responded to interferon therapy as assessed by the sustained normalization of serum ALT levels and the significant decrease of viremia levels. The response rate to interferon was independent of both initial serum viral DNA level and interferon doses. During interferon therapy, a significant decrease of M0 (wild-type pre-core sequence at pos. 1887-1908), M1 (TGG to TAG at pos. 1896) or M2 (TGG to TAG at pos. 1896, and GGC to GAC at pos. 1899) positive viral genomes was found in 48%, 42%, and 33% of patients, respectively. A higher response rate to interferon therapy was observed in patients infected with HBV genotype A (70%) or M0 positive strains (75%) as compared to patients infected with genotype D/E (40%) or M1/M2 positive strains (44%). The data support the hypothesis that pre-core defective HBV represent viral mutants with an increased capacity to resist exogenous alpha interferon. These findings emphasize that characterization of HBV genome variability prior to interferon therapy may help to predict antiviral response in HBeAg negative patients.
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PMID:Analysis of hepatitis B virus genotypes and pre-core region variability during interferon treatment of HBe antigen negative chronic hepatitis B. 882 4

Twenty-one HIV negative Japanese patients with chronic hepatitis C who had congenital bleeding disorders, 15 hemophilia A, 3 hemophilia B, 1 von Willebrand's disease, 1 afibrinogenemia and 1 thrombasthenia, were treated with 9 million units 3 times a week of natural interferon (IFN)-alpha for 6 months. They were followed, biochemically and virologically, for at least 18 months after therapy discontinuation to evaluate the long-term results. Liver biopsy, hepatitis C virus (HCV) genotyping and quantification of viral load by polymerase chain reaction (PCR) were performed to identify the predictors of a favorable response to IFN treatment. One male patient with hemophilia A dropped out because of general fatigue and was excluded from evaluation. Ten (50.0%) patients continued to be HCV RNA negative in serum together with normal ALT levels throughout the study. Subtype 1b and a high level of viremia significantly associated with an unfavorable outcome on the response to IFN although liver histology was not definitive for predicting the response. We concluded that a 6-month treatment with high doses of natural IFN-alpha was effective in inducing a long-term response without relapse of viremia in 50% of chronic hepatitis C patients with congenital bleeding disorders and that HCV subtype and pretreatment level of viremia were useful predictors of the response to IFN in treating such patients.
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PMID:A long-term follow-up study of interferon treatment for chronic hepatitis C in Japanese patients with congenital bleeding disorders. 885 94

To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-alpha therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-alpha 2a (504 million units in total) was defined as complete and sustained CR-->SR, n = 12), complete response followed by relapse (CR-->Rel, n = 17), and no response (NR, n = 10), excluding dropouts (n = 4). Patients who showed CR-->SR had a lower HCV-RNA level (0.438 x 10(6) eq/ml) compared to CR-->Rel (2.452 x 10(6) eq/ml, p = 0.008) and NR (4.882 x 10(6) eq/ml, p = 0.009). A higher proportion of patients with CR-->SR had type 2a HCV (67%) compared to the CR-->Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR-->SR, compared to those with CAH2b (p = 0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR-->SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-alpha therapy in Japanese patients with chronic hepatitis C virus infection.
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PMID:Genotype, serum level of hepatitis C virus RNA and liver histology as predictors of response to interferon-alpha 2a therapy in Japanese patients with chronic hepatitis C. 886 74

The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30 IU/l) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10(2) to 10(7) copies/50 microliters serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.
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PMID:Circulating HCV-RNA, HCV genotype, and liver histology in asymptomatic individuals reactive for anti-HCV antibody and their follow-up study. 887 94


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