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 investigated 17 patients (12 males and 5 females, ages 2 to 57 years old) with posttransfusion non-A, non-B hepatitis to determine relationships between clinical courses and hepatitis C virus (HCV) markers. The patients were grouped according to time course of abnormal serum alanine aminotransferase (ALT) levels into three categories (chronic biochemical disease, biochemically resolved chronic disease, and acute disease). Latest serum samples (1.3 to 10.8 years after blood transfusion) were used to detect antibodies against C100-3 antigen (anti-HCV) by enzyme-linked immunosorbent assay and HCV sequences by polymerase chain reaction (PCR) assay. Of the 17 patients, 13 patients (76.5%) were anti-HCV positive and 8 patients (47.1%), including one anti-HCV negative case, were positive for HCV RNA. In total, 14 patients (82.4%) were positive for either HCV markers. With respect to clinical course, HCV RNA was detected in six of eight patients (75%) with chronic biochemical disease, and in two of five patients (40%) with biochemically resolved chronic disease. HCV RNA was not detectable in convalescent sera from four patients with acute disease. These results show that there is a relationship between clinical status and HCV viremia, but that normal liver function tests do not always represent the clearance of the virus. Viremia in two patients with normal ALT level suggests that hepatitis is not only caused by viral cytopathic effects, but also by immunologic reactions against virus-infected cells. Thus, PCR is useful in determining the persistence of HCV infection as well as to diagnose anti-HCV negative HCV infection.
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PMID:Serum hepatitis C virus sequences in posttransfusion non-A, non-B hepatitis. 170 30

Sera from 30 patients with community-acquired, biopsy-proven chronic non-a,non-B hepatitis (NANBH) were tested for antibodies to the C100 protein of hepatitis C virus (HCV). The 20 patients who showed reactivity in this assay were followed prospectively for 6 months, during which time seven were treated with recombinant alpha-interferon. HCV RNA was detected by "nested" polymerase chain reaction (PCR) in 19 of the 20 anti-C100-positive sera taken at the onset of the study and also in five of the ten anti-C100-negative sera. Pretreatment viraemia levels ranged from 2 x 10(3) to 2 x 10(8) HCV genomes/ml. After 6 months of interferon, elevated serum alanine aminotransferase (ALT) levels had fallen to normal in four of the seven treated patients. In each case the response to interferon was accompanied by either a disappearance of or a decline (1 log to 8 log reduction) in viraemia. HCV genome titres in the three nonresponders and in the 13 untreated anti-C100-positive patients did not change significantly over this 6 month period. These findings confirm the aetiological role of HCV in community-acquired NANBH and suggest that quantitative PCR will become a valuable technique for monitoring the antiviral effect of interferon and other experimental treatments.
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PMID:Effect of alpha-interferon therapy on hepatitis C viraemia in community-acquired chronic non-A, non-B hepatitis: a quantitative polymerase chain reaction study. 171 96

We studied the relations between HBV heterogeneity and different phases of HBV infection and disease in 145 HBsAg-positive carriers followed-up for 28 months (range 24-60 months). Viraemia was characterized for the relative prevalence of wild-type and HBeAg minus HBVs after HBV-DNA amplification by PCR using an oligonucleotide hybridization assay. HBeAg minus HBV was detected in 27% of immunotolerant HBV carriers, in 67% of patients with chronic hepatitis B (immunoelimination phase) and in 17% of HBsAg carriers with latent infection. Serum HBV-DNA and IgM anti-HBc became undetectable and ALT levels normalized, either spontaneously or after interferon therapy in 12 (36.3%) of 33 patients with an exclusive wild-type viraemia, but only in two (5.7%) of 35 patients with homogeneous HBeAg minus HBV (p = 0.005). An HBeAg minus viraemia higher than 20% was associated, in both HBeAg- and anti-HBe-positive patients, with HBV-induced liver disease and an unfavourable outcome of hepatitis. These findings suggest that surgence of HBeAg defective HBV is a virus strategy to survive under peculiar conditions dictated by the interplay between HBV and the host's immune system. The HBeAg/anti-HBe serological status is determined not only by the extent of virus replication and integration of HBV-DNA into cellular DNA but also by heterogeneity of HBV. The study of HBV heterogeneity in baseline sera of patients undergoing antiviral therapy appears to have a predictive value of the outcome of HBV infection in the single patient.
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PMID:'e' antigen defective hepatitis B virus and course of chronic infection. 182 19

To investigate the effect of human immunodeficiency virus type 1 (HIV-1) infection on subsequent hepatitis B virus (HBV) infection, HIV antibody was sought in homosexual men who developed HBV infection during a hepatitis B vaccine trial. Among 134 unvaccinated HIV-1-negative men, 7% became HBV carriers, 64% had viremia, and 42% had clinical illness. Among vaccinated HIV-1-negative men, HBV infection severity decreased with number of vaccine doses administered. When adjusted for prior hepatitis B vaccination status, persons with HIV-1 infection preceding HBV infection had a significantly higher risk of developing HBV carriage, viremia, prolonged ALT elevation, and clinical illness. Among HIV-1-infected men, the risk of HBV carriage was increased in unvaccinated persons (21%) and those who failed to respond to vaccination (31%) and further increased in those who received vaccine doses at the time they developed new HBV infection (56%-80%), suggesting inactivated hepatitis B vaccine may temporarily impair the immune response to HBV infection in HIV-1-infected persons. HIV-1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow-up of men who became HBV carriers.
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PMID:Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. 182 15

Hepatitis C virus (HCV) is the major etiologic agent associated with non-A, non-B hepatitis. This study was designed to assess virologic and serologic markers in hemophiliacs exposed to non-heat-treated and/or virus-inactivated plasma derivatives. Serial bleeds from 48 hemophilic patients were analyzed for the presence of HCV viral RNA sequences as detected by polymerase chain reaction (PCR) and antibodies to structural (core) and nonstructural (C-100 and 33C) proteins by specific dot immunoblot assay. All patients exposed to non-heat-treated products, and four of six patients exposed only to virus inactivated products, had evidence of HCV infection. However, over the 5-yr study period, six exposed patients (13%) consistently lacked detectable anti-C-100 and seven (15%) lost this antibody. HCV viremia (PCR positive) was found in 91% of exposed patients, and was significantly more frequent in HIV seropositive hemophiliacs (P less than 0.05). Six patients had high antibody level to HCV and elevated ALT, but appeared to clear viremia. Four hemophiliacs were HCV seropositive but lacked detectable viremia. These data indicate that hemophiliacs remain persistently infected by HCV and that antibody to the core antigen of HCV is a reliable marker of this transfusion transmissible agent.
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PMID:Evidence for persistent hepatitis C virus (HCV) infection in hemophiliacs. 193 52

Four chimpanzees have been infected with three different inocula containing "non-A, non-B" hepatitis virus(es). After inoculation, serial studies established the presence of antigenemia or viremia (or both) by radioimmunoassay with high-affinity monoclonal antibodies directed toward separate and distinct determinants on hepatitis B surface antigen (HBsAg) and by molecular hybridization analysis using a cloned hepatitis B virus (HBV) DNA probe. In contrast to results observed during HBV infection, elevations in serum alanine aminotransferase values indicate that liver injury preceded antigenemia by several weeks. Thus, the time between inoculation and development of antigenemia (incubation period) varied from 64 to 190 days and, in some cases, single or multiple episodes of antigenemia or viremia occurred in the absence of elevated aminotransferase levels. In this study, two chimpanzees were high-titer positive for antibodies to HBsAg (anti-HBs) from previous infection with HBV, suggesting that the antigenic composition of HBV-related virus(es) is substantially different from that of HBV, since naturally occurring anti-HBs antibodies were not protective. Demonstration of HBV-related virus(es) by the methods used in this study of experimental hepatitis infection in chimpanzees should now permit detection, isolation, and characterization of these previously elusive agents.
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PMID:Detection and transmission in chimpanzees of hepatitis B virus-related agents formerly designated "non-A, non-B" hepatitis. 681 47

Ninety consecutive patients with chronic hepatitis C were included in a randomized, uncontrolled trial to compare the efficacy of two treatment regimens, 10 MU (group A) vs 5 MU (group B), of lymphoblastoid interferon, in a step-down schedule for 24 weeks. All of the patients had antibodies against the hepatitis C virus, and all but one were HCV RNA positive in serum. The origin of the infection was attributed to blood transfusion in 30 patients and classified as sporadic in 60 patients. During treatment reduction in the ALT levels as well as the elimination of viraemia was observed in both treated groups, although these changes did not correlate significantly with the interferon dose. Nine months after the end of therapy, a sustained response was achieved in 13.6% (12/88) of the patients. Relapse in group B (87.5%) was significantly higher than in group A (59.1%). The percentage of cases which remained with undetectable HCV RNA was significantly higher for the sustained responders (66.7%) than for the non-responders (11.8%) and relapser patients (2.4%). Repeated liver biopsies showed an overall significant reduction of all the subindices of histological activity from patients with sustained response, except for fibrosis. In short: the 10 MU dosing regimen of lymphoblastoid interferon was as efficient as the 5 MU dose as it brought about a similar improvement in ALT levels, histological activity and elimination of viraemia, albeit 10 MU proved significantly more effective in the prevention of a relapse among the responders after 24 weeks therapy.
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PMID:Comparative study of two high doses of lymphoblastoid interferon in the treatment of chronic hepatitis C: influence on the levels of ALT, viraemia and histologic activity. 748 45

In November 1989, Japanese Red Cross Blood Centres started screening for hepatitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61-80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2) and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with > or = 2(12) agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predictive value of screening tests for persistent hepatitis C virus infection evidenced by viraemia. Japanese experience. 750 73

Polymerase chain reaction (PCR) was applied to detect HCV-RNA in 75 hemodialyzed patients. Anti-HCV status was determined by ELISA-2 and by RIBA-2 for reactive samples by ELISA. ALT levels were monthly determined during the year preceding the end of the study. For 60 patients, anti-HCV serology was known since 1989 and 39 of them were tested for the presence of HCV-RNA at least four times during the 2 preceding years. The 9 patients who were negative for anti-HCV antibodies were negative by PCR. Of the 7 patients with an indeterminate profile by RIBA-2, 3 were positive by PCR: 1/1 with C-33c band only and 2/6 with C22-3 band only. Of the 59 patients reactive by RlBA-2, 57 were HCV-RNA positive. Of the 2 HCV-RNA negative patients, one had been PCR positive before interferon therapy. Of the 38 patients without acute hepatitis tested by PCR on 5 successive samples, all the specimens of 11 and 23 patients were HCV-RNA negative and HCV-RNA positive respectively. In 4 patients, a transient viremia was observed. The group of HCV-RNA positive patients had mean ALT levels greater than those who were negative. A correlation was established between HCV infection and both the time on dialysis and the number of blood transfusions. A high concordance (97%) was observed between antibodies to HCV and HCV-RNA.
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PMID:[Correlation between hepatitis C virus (HVC) RNA and anti-HVC antibodies in a hemodialysis population]. 750 79

The clinical and epidemiological relevance of circulating antibodies to hepatitis C virus (HCV) in hemodialysis patients is uncertain, since clinical signs of infection are often mild or absent, with alanine aminotransferase (ALT) values that are virtually always normal, and liver biopsies are only rarely performed. Determination of HCV RNA in serum is therefore critical for distinguishing chronic HCV infection from previous exposure to the virus. We studied HCV viremia by reverse transcription polymerase chain reaction (RT-PCR) in the 5'-noncoding region of the viral genome in 77 dialysis patients who were screened for anti-HCV by a second-generation enzyme-linked immunosorbent assay (the enzyme immunoassay II; Ortho HCV, 2nd generation, Ortho Diagnostic Systems Raritan, N.J.) and a second-generation recombinant immunoblot assay (Chiron Corporation and Ortho Diagnostic Systems) and prospectively evaluated for ALT elevations over a period of 5 years. Of 77 patients tested, 29 (38%) had active infection as shown by a positive PCR assay result, and of these, 26 were anti-HCV positive. Although a good correlation was found between circulating anti-HCV and HCV RNA in serum, 10 (28%) of 36 anti-HCV-positive patients were HCV RNA negative by PCR, suggesting either low levels of viremia or past exposure to HCV and subsequent recovery. On the other hand, 3 (7.3%) of 41 anti-HCV-negative patients had HCV RNA in their sera, indicating seronegative HCV infection. The ALT level had no predictive value for HCV infection, because it was repeatedly normal in 18 (62%) of 29 viremic patients. HCV genotyping was also performed and indicated that all four known genotypes of HCV were present in our group. In conclusion, serological assays are reliable for detecting exposure to HCV in hemodialysis patients; however, direct identification of the viral genome is required to document current infection.
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PMID:Virological features of hepatitis C virus infection in hemodialysis patients. 750 92


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