Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of circulating hepatitis C virus genome (HCV-RNA), elevated ALT levels and antibodies to an NS5-derived synthetic peptide have been examined in 13 subjects with isolate positivity for antibodies to the HCV core antigen (C22) on RIBA-2 testing. All subjects were followed up for 8-18 months (mean 12.4 months). In seven subjects (54%), intermittent or persistent viremia was associated with abnormal ALT levels (6 subjects) and with positivity for antibodies to NS5-peptide (6 subjects). On the other hand, in 6 out of 13 subjects (46%) no viral replication, no liver cytonecrosis and no antibodies to NS5 were found. It is concluded that isolate reactivity to C22 by RIBA-2 is a heterogeneous condition that corresponds to two distinct categories of subjects: those with active HCV infection and those without evidence of virus replication. Although HCV-RNA determination is the most reliable means of identifying HCV carriers, antibodies to NS5 can be a useful marker of virus activity. In fact, antibodies to NS5 were detected in 6 out of 7 viremic patients, compared to 0 out of 6 non-viremic patients (P = 0.004). It remains to be elucidated whether the isolate reactivity to core antigen found in non-viremic subjects represents a specific, HCV-induced antibody response, or is an unrelated crossreactivity.
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PMID:Isolate antibody to hepatitis C virus core antigen (C22) by RIBA-2: correlation with HCV-RNA and anti-NS5. 826 Aug 66

The antiviral effect of natural interferon (IFN)-alpha on chronic hepatitis C virus (HCV) infection was estimated by determining quantitative changes in serum HCV-RNA compared with the serum alanine aminotransferase (sALT) improvement; the relationships of responses to IFN according to the dose and period of IFN therapy were defined to determine an appropriate IFN therapy protocol. Twenty-two patients with chronic hepatitis C were given natural IFN-alpha and in 16 (72.7%) patients the viraemia was suppressed during therapy. Five (27.7%) of them sustained the disappearance of HCV-RNA for more than 6 months after therapy accompanied with a prolonged sALT improvement. Pre-treatment viraemia levels in 5 complete responders with "complete suppression" of viraemia were significantly lower than in 11 patients with a transient loss or a decline of HCV-RNA. A favorable antiviral response was closely associated with a high total dose of IFN-alpha and a long duration of IFN therapy.
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PMID:Appropriate interferon-alpha therapy for chronic hepatitis C: an assessment by quantitative changes in serum hepatitis C virus-RNA. 828 27

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770 in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha treatment. Mean viremia level was comparable among the 30 responders (5,644 +/- 8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatitis C viremia in chronic liver disease: relationship to interferon-alpha or corticosteroid treatment. 829 85

To detect hepatitis D virus (HDV) RNA in asymptomatic HDV-infected risk groups, Northern blot hybridization was carried out using a strand-specific riboprobe. Univariate and multivariate analyses were carried out to evaluate factors associated with HDV viremia and elevated transaminase levels in these subjects. Two (15%) of 13 antibody to HDV (anti-HDV) -positive intravenous drug addicts, 15 (33%) of 45 anti-HDV positive prostitutes, and 6 (40%) of 15 anti-HDV positive brothel goers had detectable serum HDV RNA. Older age (> 31 years old) was negatively associated with HDV RNA (P < .04), while hepatitis B e antigen (HBeAg) was positively associated with it (P < .002) in univariate analysis. Only HBeAg was still significant in multivariate analysis (P < .05). Of the 76 asymptomatic anti-HDV positive case, 28 (37%) had mildly elevated serum ALT levels and only 5 (7%) had ALT levels more than twice normal (> 80 U/L). HBeAg (P < .05) and HDV RNA (P < .02) were two factors associated with ALT elevation in univariate analysis, and HDV RNA was the only significant factor in multivariate analysis (P < .005). In summary, active replication of HBV seemed to be of help for the assembly of HDV and viremia. However, active replication of HDV was associated mostly with mildly elevated ALT levels in these subjects. These cases may represent a particular group in the disease spectrum of HDV infection.
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PMID:Factors associated with viremia and elevated transaminase levels in asymptomatic hepatitis D virus-infected risk groups. 830 25

Hepatitis C virus (HCV) is a major cause of post transfusion non-A, non-B hepatitis. The virus contains a positive-strand RNA genome comprised of approximately 9,400 nucleotides. HCV E2/NS1 is probably an envelope glycoprotein (E2). The E2 hypervariable domain appears to contain isolate-specific antibody-binding linear epitopes. Recently, comparative sequence analysis of all the complete and partial HCV sequences published to date indicates that known genotypes of HCV can be classified into six basic groups. We report here that the prevalence of HCV-I, HCV-II, and a mixed form are 77.2%, 11.4%, and 11.4%, respectively. Patients with anti-HCV and HCV-RNA positive chronic active hepatitis received 6MU of interferon-alpha or beta everyday for two weeks followed by 6MU thrice a week for 14 weeks. Complete response to interferon treatment was defined as an ALT level normalized within six months after the end of treatment and maintained within the normal limit for an additional six months. Complete response was found in 42.9% of patients treated for 16 weeks. In a six month follow-up of the complete responders, clearance of viremia was observed in 90.3% at the end of interferon treatment and in 71.0% six months after the end of interferon treatment.
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PMID:[Hepatitis C]. 834 54

Amplification of RNA by the polymerase chain reaction (PCR) is normally a two-step process requiring separate enzymes and buffer conditions. We describe a combined reverse transcription-PCR (RT-PCR) assay for hepatitis C virus (HCV) RNA amplification in which a single enzyme and buffer condition are used. In this assay, both the RT and PCR steps are carried out with the thermoactive DNA polymerase of Thermus thermophilus. A transcription vector containing HCV sequences has also been constructed to generate quantifiable HCV RNA templates that can be used to optimize reaction conditions and to assess the efficiency of amplification. Amplification from < or = 100 copies of RNA was detected reproducibly by gel electrophoresis. The assay sensitivity was increased to 10 RNA copies by hybridization to a probe. The patterns of viremia in three individuals infected with HCV were examined by amplification of HCV RNA from plasma samples collected serially over a period of 1 year. These results were correlated with the times of seroconversion and the onset of rise in levels of alanine aminotransferase in serum. In all three subjects, HCV RNA was detected prior to seroconversion and the initial rise in levels of alanine aminotransferase in serum. Upon seroconversion, HCV RNA fell to a level below the detection limit of the assay. This pattern of transient viremia appears to be characteristic of acute, resolving HCV infections. The combined RT-PCR assay is a sensitive method which circumvents the problems associated with PCR amplification of RNA. Using this assay, we demonstrated that three donors infected by the same index case all have similar patterns of viremia.
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PMID:Detection of hepatitis C virus RNA by a combined reverse transcription-polymerase chain reaction assay. 838 51

Viremia in hepatitis A viral (HAV) infection is said to be limited to pre-symptomatic period. However, it is not clear how long viremia lasts in human infection due to the lack of a simple and sensitive detection system. In an attempt to find HAV genome in patients' sera, we used the RT-PCR method by setting a pair of primers in the 5' non-coding region. While in most cases HAV-RNA was detected only before alanine aminotransferase (ALT) reached peak levels with this sensitive system, the viral genome was observed in some patients' sera even after ALT reached peak levels. Some patients also had HAV viremia after seroconversion to HAV antibody. These results show that viremia in HAV infection lasts longer than has been previously thought, and give a warning of possible secondary blood-borne infection.
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PMID:Duration of viremia in human hepatitis A viral infection as determined by polymerase chain reaction. 839 May 58

HCV RNA was determined by the polymerase chain reaction (PCR) in 41 haemodialysed patients with a known anti-HCV status (ELISA and RIBA-2) and a monthly alanine aminotransferase (ALT) level determination. No histological examination of the liver tissue was available. Four samples from each patient were collected at 6 month intervals for 18 months. Seven patients negative for anti-HCV during the entire follow-up gave negative PCR results on the four samples. Two patients who were anti-HCV-negative upon entry into the study seroconverted to HCV during follow-up. HCV RNA was detected during the acute phase of hepatitis. HCV RNA was no longer detectable after antiviral therapy was administered to one patient. Out of 27 anti-HCV-positive patients, 24 had persistent viraemia, 2 had transient viraemia (1 sample PCR-negative and 3 samples PCR-positive) and 1 was PCR-negative on the 4 samples. Thirteen of the 26 viraemic patients had a normal ALT level during the preceding 3 years. Three patients with a C22-3 band alone by RIBA-2 were negative by PCR, whereas two patients with a C33-c band alone were PCR-positive on the four samples. These results suggest that HCV viraemia was strongly associated with anti-HCV in haemodialysed patients with or without biological hepatitis.
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PMID:Detection of hepatitis C virus by polym erase chain reaction in haemodialysed patients in relationship to anti-HCV status. 839 76

Five cynomolgus monkeys (Macaca fascicularis) developed hepatitis after inoculation with a prototype strain of hepatitis E virus (HEV) from Pakistan. Although all 5 monkeys displayed liver enzyme elevations, viremia, virus secretion in feces, and seroconversion, two different patterns of these parameters were observed. For 4 monkeys, increased alanine aminotransferase (ALT) activity was first observed on days 21-26, viremia occurred before and during enzyme elevation, and the animals seroconverted coincidentally with the end of viremia or shortly thereafter. One of these monkeys had a more severe hepatitis, with peak ALT values more than twice the peak levels of the other monkeys. The fifth monkey developed biphasic hepatitis with peaks of ALT activity on days 26 and 54. In this case, viremia and seroconversion were correlated only with the second peak of enzyme elevation and liver histopathology only with the first peak. Viral shedding in this fifth animal lasted two times longer than in other animals.
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PMID:Variation in course of hepatitis E in experimentally infected cynomolgus monkeys. 850 18

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant recipients. To assess the efficacy and the safety of therapy with interferon alpha (IFN alpha) in such a population we conducted a prospective study where 16 kidney transplant recipients with chronic hepatitis C received recombinant IFN alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All the patients had stable renal function for at least 1 year (mean serum creatinine 125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the beginning of the study. In 15 patients serum alanine aminotransferase (ALT) levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P = 0.0044). ALT remained in the normal range as long as IFN alpha was continued. Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to 88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end of IFN alpha therapy remained positive in all the patients who scored positive at the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight loss) were frequent leading to four patients dropping out of the study. The haematological tolerance was moderate. The major concern was the increase in serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only six patients experienced renal failure occurring 45-168 days after the beginning of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered interstitial inflammatory cellular infiltration and moderate mesangial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preliminary results of treatment of chronic hepatitis C with recombinant interferon alpha in renal transplant patients. 852 7


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