Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:2.6.1.2 (
alanine aminotransferase
)
26,722
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thirty-nine of 61 prospectively followed patients who had had acute non-A, non-B hepatitis in 1978 were clinically reexamined in 1991 and tested for antibodies to hepatitis C virus (anti-HCV) with a second generation ELISA and RIBA and for HCV RNA by PCR.
Acute hepatitis C
was diagnosed in stored sera from 1978 in 24 patients, who were found still to be anti-HCV positive in 1991, and 16 of them were also HCV RNA positive. The majority of anti-HCV positive patients with or without HCV RNA had elevated serum
ALT
levels 13 years after onset of their acute hepatitis C. After 13 years follow-up, 1.6% of the patients had died of end-stage liver disease, 8% of anti-HCV positive patients had histologically confirmed liver cirrhosis, 79% of anti-HCV positive patients were judged to have chronic infection, whereas 21% seemed to have recovered. To conclude, we found that a majority of our patients with acute symptomatic hepatitis C continued to be viraemic 13 years after onset of hepatitis C, and that all continued to be anti-HCV positive by second-generation ELISA.
...
PMID:Outcome of acute symptomatic non-A, non-B hepatitis: a 13-year follow-up study of hepatitis C virus markers. 750 44
Acute hepatitis C
takes a chronic course in 50-80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-alpha2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested using PCR prior to treatment, three times weekly during the first two weeks of treatment, and then once weekly until the end of therapy. During the 15-month follow-up, HCV-RNA tests were performed monthly up to month 6 and every two to three months thereafter. Twenty-four patients were enrolled at the time of writing; age ranged from 18 to 76 years (mean = 32), and nine patients were men. All patients presented with cholestatic hepatitis; 19 were actively abusing intravenous drugs, four had no known parenteral exposure, and one was a medical laboratory technician. All patients were anti-HCV positive, HCV-RNA positive, and HIV negative. Five patients were infected with genotype 3, five with genotype 1a, five with genotype 1b, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients exhibited normalized serum transaminase concentrations within 18-43 days; HCV-RNA became negative in all patients within 4-12 days. Toxicity did not exceed grade 1 and disappeared within three days of treatment. In the follow-up period, which ranged from six to 29 months (mean = 19.5 +/- 10.4), serum
ALT
concentrations remained normal and HCV-RNA remained negative in all patients except two dropouts and two patients who developed relapsing disease after having been HCV-RNA negative for three and eight months, respectively. In both patients, the same HCV genotype 3 reemerged. Serum
ALT
concentrations ranged from 531 to 1940 IU/liter (mean = 1055; normal < 22). Concentrations of HCV-RNA (Quantiplex; Chiron, Emeryville, California) were < 3.5 x 10(5) eq/ml in nine of 14 PCR-positive patients. In the other five patients, concentrations ranged from 10.4 x 10(5) eq/ml to 131.6 x 10(5) eq/ml (mean = 69.6 x 10(5)). No correlation was observed between HCV-RNA concentrations and serum
ALT
concentrations at presentation (r = 0.331; P = 0.67) and total dose of interferon-alpha2b administered until normalization of
ALT
(r = -0.088; P = 0.74). Twenty-two of 24 patients completed treatment (two were noncompliant). Of these, 20 achieved a complete response (HCV-RNA negative for at least six months). Two of these patients relapsed, and 18 (90%) remained HCV-RNA negative for 18.65 (+/-9.7) months. These findings suggest that high-dose interferon-alpha2b is well tolerated and effective in preventing a chronic course of hepatitis C infection.
...
PMID:High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a pilot study. 901 81
In a 4-year follow-up study, patients with acute sporadic non-A, non-B (NANB) hepatitis were evaluated to determine the etiology and natural history of the disease.
Acute hepatitis C
virus (HCV) was detected in 13 of 43 (30%) of patients, anti-hepatitis E virus (HEV) IgG in 5 (12%), and 25 (58%) were considered non-A-E. The HCV RNA was detected in all HCV patients but none of the non-A-E cases. The initial clinical and biochemical presentation of the HCV and non-A-E cases was quite similar, although 2 of the non-A-E patients had severe disease. The 5 patients who were found to be anti-HEV IgG-reactive recovered within 6 months of follow-up. Of the 13 HCV cases,
alanine transaminase
(
ALT
) levels returned to normal in 7 (53. 8%), while 6 (46.2%) continued to show abnormal
ALT
after 6 months of follow-up. However, 9 (69.2%) of them remained HCV-RNA-positive, denoting virological/biochemical dissociation. Long-term follow-up showed a reappearance of HCV RNA in 2 of the 4 patients who were in virological remission performing 84% of chronicity rate. Acute non-A-E hepatitis patients were less likely to evolve toward chronicity, as compared with acute HCV cases (16% vs. 84%; P =.0001). Only 4 (16%) of the non-A-E patients were hepatitis G virus (HGV)-RNA-positive. Concerning risk factors for acquiring parenterally transmitted viruses, tattooing was the only one that could be associated with HCV transmission (P =.002). No risk factors could be identified for putative non-A-E virus transmission. Liver biopsies performed for chronic HCV patients showed a variable degree of inflammation, while the non-A-E patients presented less severe histological disease.
...
PMID:Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: etiology and natural history. 1038 69
The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%).
Acute hepatitis C
is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum
alanine aminotransferase
(
ALT
) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum
ALT
levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in
ALT
levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
...
PMID:Course and outcome of hepatitis C. 1240 73
Acute hepatitis C
often progresses to chronic infection (70%). In this clinical study, we evaluated if early treatment with peginterferon alfa-2b can prevent acute hepatitis C from developing into a chronic disease. Six patients with acute hepatitis C, based on a well-documented hepatitis C virus (HCV) seroconversion with high
alanine aminotransferase
(
ALT
) levels (> 10 x ULN) and persistent HCV RNA titers after 3 months from disease onset, were consecutively treated with peginterferon alfa-2b at 1.5 microg/kg/weekly/sc for 24 weeks. The viral load was quantified by PCR assay. Response was defined as undetectable HCV RNA and normal
ALT
levels at the end of therapy and after a 6-month follow-up. All patients completed therapy; at the end of therapy, 5/6 patients (83%) responded and no relapses were observed during follow-up. No correlation was found between treatment response and pretreatment viral load, viral genotype, and interval between acute infection diagnosis and start of therapy.
...
PMID:Peginterferon alfa-2b treatment for patients affected by acute hepatitis C: presentation of six case reports. 1575 Jul 57
Acute hepatitis C
virus (HCV) infection evolves to chronicity in 50-84% cases. Treatment with interferon-alpha (IFN-alpha) was repeatedly found to provide sustained cure rates higher than that in chronic HCV infection, but the optimal treatment strategy has not yet been defined. In a multicentre open-label study, we investigated the therapeutic performance of a short course of pegylated (peg) IFN-alpha in patients with acute HCV hepatitis. Peg IFN-alpha2b, 1.0-1.5 micro g/kg weekly, was administered for 12 weeks. Forty-six patients were enrolled; 26 of them were intravenous drug users. Eleven patients had jaundice. Treatment was started within 1-90 days from the peak
alanine aminotransferase
. Treatment was well tolerated with a single dropout (2%). Thirty-three of 46 patients (72%) had a sustained virological response (SVR) after a 6 months post-treatment follow-up, 8 (17%) relapsed after treatment and 4 were nonresponders (9%). A lower peak viraemia, receiving at least 1.2 micro g/kg of peg IFN-alpha, and a negative HCV-RNA at week 4 and week 12 were predictors of SVR. Thus, in patients with early (week 4) viral response, a short course of peg IFN-alpha at a weekly dose >1.2 micro g/kg, may be a valuable option for the treatment of acute HCV hepatitis.
...
PMID:A short course of pegylated interferon-alpha in acute HCV hepatitis. 1724 51
Acute hepatitis C
in immunocompetent individuals is rarely symptomatic and rarely biopsied. Thus, the histologic descriptions of acute hepatitis C remain limited. The histology of 5 cases of acute hepatitis C in adults were studied by selecting cases from the consult and surgical pathology files of a single institution. The 5 individuals, 3 males and 2 females, had an average age at biopsy of 50+/-17 years. They presented with jaundice and other nonspecific abdominal symptoms. The time interval from clinical presentation to biopsy ranged from 2 to 18 weeks. The average
alanine aminotransferase
/aspartate aminotransferase/alkaline phosphatase at the time of biopsy was 308/73/85 U/L. The average total bilirubin was 5.2 mg/dL. Each individual had a single liver biopsy. The histologic findings of the 2 cases biopsied in close temporal proximity to the initial clinical presentation showed similar histologic findings of mixed portal infiltrates with lymphocytes and neutrophils along with bile ductular proliferation that raised the possibility of down stream biliary tract disease. The lobules showed canalicular cholestasis and mild to moderate inflammation. In the third and fourth case, obtained 8 weeks after presentation, the biopsies showed mild to moderate portal and lobular lymphocytic inflammation, findings that were also present in the last case, obtained 18 weeks after presentation. In conclusion, early after acute hepatitis C viral infection, biopsies can have a cholestatic pattern whereas later biopsies tend to show mild nonspecific portal and lobular lymphocytic inflammation. Proper histologic diagnosis can be aided by an awareness of the various histologic findings, which vary depending on the time interval from clinical symptoms to biopsy.
...
PMID:Histology of symptomatic acute hepatitis C infection in immunocompetent adults. 1805 33
Symptomatic acute hepatitis C occurs in only about 15% of patients who are infected with hepatitis C virus (HCV).
Acute hepatitis C
is most often diagnosed in the setting of post-exposure surveillance, or seroconversion in high-risk individuals (eg, health-care professionals or injecting drug users) previously known to be seronegative. Although transmission via transfusion and injecting drug use has declined in developed countries, unsafe blood products and medical practices continue to increase transmission of HCV in many developing countries. Clinically, acute hepatitis C can increase concentrations of
alanine aminotransferase
to ten times the upper limit of normal but almost never causes fulminant hepatic failure. Diagnosis of HCV infection in the acute phase is difficult since production of antibodies against HCV can be delayed by up to 12 weeks, and about a third of infected individuals might not have detectable antibody at the onset of symptoms. Therefore, testing for HCV RNA by PCR is the only reliable test for the diagnosis of acute infection. Symptomatic patients with jaundice have a higher likelihood of spontaneous viral clearance than do asymptomatic patients, and thus should be monitored for at least 12 weeks before initiating antiviral therapy. By contrast, asymptomatic patients have a much lower chance of spontaneous clearance, and might benefit from early antiviral therapy. Antiviral therapy for 12 weeks is generally effective in treating patients who are HCV RNA negative after 4 weeks of treatment; lengthier courses could be needed for those who relapse or fail to show early virological clearance.
...
PMID:Acute hepatitis C. 1865 11
Acute hepatitis C
virus (HCV) infection is often a clinically silent infection, and is therefore rarely detected. A high index of clinical suspicion in addition to careful serological and virological assessment is required to identify the disease, and to determine the eventual clinical outcome after primary infection; the minority of acutely infected individuals spontaneously control viremia in long term whilst the majority become persistently infected. Here, we describe the clinical presentation of acute HCV infection and the patterns of viremia and liver
alanine transaminase
levels (ALT) observed. We discuss the serological and virological assessment and potential pitfalls in accurately diagnosing acute HCV. Good prospective studies that identify host and virological factors that determine clinical symptoms and disease outcome are difficult to perform due to the asymptomatic nature of infection, but some progress has been made in this field. Host factors including gender, age at time of infection, prior resolution of infection, symptomatic infection and host immune responses, and viral factors such as the nature of the infecting quasispecies and more speculatively viral genotype, are some features that have been correlated with disease outcome. In spite of this, on an individual patient level, it is currently not possible to predict those that will resolve infection. Identifying, in detail therefore, those factors that are responsible for viral control remains an important research goal not only to aid clinical management but also to develop effective treatment and vaccination strategies.
...
PMID:Acute hepatitis C: clinical aspects, diagnosis, and outcome of acute HCV infection. 1867 89
Acute hepatitis C
virus (HCV) infection is being acquired undetected among HIV-infected individuals. A practical way to regularly screen HIV-infected patients for acute HCV irrespective of perceived risk or symptoms is needed. We piloted implementation of an acute HCV screening strategy using routine HIV clinical care schedules and the least costly blood tests, in a Rhode Island HIV care center. Study participants had ongoing HCV risk, completed questionnaires encompassing risk behaviors and perception of risk, and were screened with quarterly
alanine aminotransferase
(
ALT
).
ALT
rise triggered HCV RNA testing, with pooled rather than individual specimen HCV RNA testing for underinsured participants. Participants were primarily older, college-educated men who have sex with men (MSM) with history of sexually transmitted infection other than HIV. One of 58 participants developed acute HCV in 50 person-years of observation for an annual incidence of 2.0% per year (95% confidence interval [CI] 0.05-11.1%). The majority (54%) of MSM did not perceive that traumatic sexual and drug practices they were engaging in put them at risk for HCV. Unprotected sex often occurred under the influence of drugs or alcohol. Self-reported HCV risk and participation in several risk behaviors declined during the study. It was possible to collect frequent ALTs in a busy HIV clinic with 71% of total projected ALTs obtained and 88% of participants having at least one
ALT
during the 9-month follow-up period. All instances of
ALT
rise led to reflexive HCV RNA testing. Tracking quarterly
ALT
for elevation to systematically prompt HCV RNA testing before seroconversion is a promising approach to screen for acute HCV in a real-world HIV clinical setting.
...
PMID:Acute hepatitis C virus in an HIV clinic: a screening strategy, risk factors, and perception of risk. 2185 7
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