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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between May 1996 and June 1998, 210 members of a cohort of 1,667 hepatitis C virus (HCV)-infected injection drug users (IDUs) were selected for liver biopsy procedure after stratification based on 2 consecutive serum alanine transaminase (ALT) levels. Liver histology, which could be fully evaluated for 207 subjects, was classified by using the modified Ishak scores. At the time of biopsy, the median age of subjects was 41.3 years and the median estimated duration of HCV infection was 20.7 years; 94% were African American; 78% men; 31% were human immunodeficiency virus (HIV) seropositive; and 76% had HCV genotype 1a or 1b. Total modified histologic activity index (MHAI) scores ranged from 0 to 9, and 26.6% had a total MHAI score of 5 or greater. Persons with a total MHAI score of 5 or greater were more likely to be HIV infected (P =.04). Higher fibrosis, indicated by Ishak modified fibrosis scores of 3 to 6, was present in 10.1% of subjects and was found more often in those older than 46 years of age (the highest quartile) (P <.01). Both fibrosis scores of 3 or greater and total scores of 5 or greater were associated with elevated ALT, aspartate transaminase (AST), and gamma-glutamyl transpeptidase (GGT) levels (P <.01). When serial values were considered, the results of liver enzyme testing could reduce the probability of an IDU having a fibrosis score of 3 or greater from 10% to 3%. In conclusion, these data indicate that severe liver disease is uncommon in this urban, HCV-infected IDU cohort, especially in younger persons and those with repeatedly normal liver enzymes.
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PMID:Severity and correlates of liver disease in hepatitis C virus-infected injection drug users. 1198 75

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.
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PMID:Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection. 1199 75

Forty-six cats with clinical haemobartonellosis were studied; 75 per cent of the cats of known age were two-and-a-half years old or younger, 50 per cent were intact males and 19.5 per cent were castrated males. The predominant signs of the disease were tachypnoea, lethargy, depression, anorexia, infestation with fleas, pale mucous membranes, icterus, emaciation, dehydration, splenomegaly, anaemia, leucocytosis, increased activities of alanine aminotransferase and aspartate aminotransferase, and azotaemia. Thirty-eight per cent of the cats that were tested for feline leukaemia virus (FeLV) antigen were positive, and 22 per cent of those tested for feline immunodeficiency virus (FIV) antibodies were positive. The prevalence of both FeLV and FIV was much higher than in the general Israeli cat population. The cats infected with both Haemobartonella felis and FeLV had a significantly lower body temperature, were more anaemic and the mean cell volume of their erythrocytes was greater than in the cats with haemobartonellosis alone.
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PMID:Retrospective study of 46 cases of feline haemobartonellosis in Israel and their relationships with FeLV and FIV infections. 1216 25

To determine the incidence of hepatotoxicity and to investigate whether plasma concentrations of nevirapine, in addition to other risk factors, could predict hepatotoxicity during treatment with nevirapine-containing regimens, we conducted a retrospective analysis with data from 174 individuals infected with human immunodeficiency virus-1 (HIV-1). During regular visits to the clinic, blood samples were collected for the determination of nevirapine plasma concentrations and clinical chemistry parameters including liver enzymes (LEs) and total bilirubin (TBR). Severe hepatotoxicity was defined as a grade > or =3 elevation in at least one of the tested LEs or TBR levels while on therapy. Analysis of predictive factors was focused on increases in aspartate aminotransferase (ASAT) and/or alanine aminotransferase (ALAT) to grade > or =2. Grade > or =3 elevation developed with an incidence of 0.15 per patient year (PY); only 3.4% of the patients developed grade > or =3 values for ASAT and/or ALAT (incidence 0.03 per PY). We found that patients who use a protease inhibitor (PI) in a nevirapine-containing regimen and patients who have chronic hepatitis B (HBV) infection are at a higher risk for the development of increases in ASAT and/or ALAT to grade > or =2. In contrast, the plasma concentration of nevirapine does not appear to be a predictive factor in this study population.
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PMID:Hepatotoxicity following nevirapine-containing regimens in HIV-1-infected individuals. 1222 Sep 74

Human immunodeficiency virus (HIV)-infected patients frequently present with elevated levels of serum transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]). This has often been attributed to the hepatic effects of antiretroviral (ARV) drugs, including nonnucleoside reverse-transcriptase inhibitors (NNRTIs). A review of cohort studies investigating the incidence of hepatotoxicity among patients receiving ARV therapy suggests that the overall rate of ALT and/or AST elevations is similar among all ARVs. The rate of severe hepatotoxicity, ALT and/or ASTlevels >5 times the upper limit of normal (ULN), during therapy with NNRTIs is relatively low but may be significantly higher in patients with concurrent chronic viral hepatitis (hepatitis B or C). A comprehensive analysis of 17 randomized clinical trials of nevirapine demonstrated that 10% of all nevirapine-treated patients developed elevated levels of ALT and/or AST >5 times the ULN; however, almost two-thirds (6.3% of nevirapine-treated patients) of these elevations were asymptomatic. Symptomatic hepatic events were seen in 4.9% (3.2%-8.9%) of nevirapine-treated patients.
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PMID:Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. 1547 67

Hepatitis C virus (HCV) infection is uncommon in children, and its natural history is still unknown. Our aim was to analyze exposure to HCV in 48 infants and children in Argentina and to evaluate consecutive samples in 26 of them to study the outcome of HCV infection in early stages. HCV viremia, as determined by reverse transcription-PCR (RT-PCR) from the 5' untranslated region, showed continuously positive, occasionally positive, and negative patterns during follow-up. Restriction fragment length polymorphism was performed on RT-PCR-positive samples to evaluate HCV genotype. Genotype 1 turned out to be predominant, and no patient displayed a genotype shift during the observation period. Perinatal HCV infection was predominantly observed in patients born to mothers coinfected with HCV and human immunodeficiency virus. HCV viral load was detected by means of the AMPLICOR MONITOR, version 2.0, kit. No correlation was observed between HCV viral load and alanine aminotransferase and aspartate aminotransferase levels, although we detected a trend towards higher levels among patients displaying consecutive positive HCV RT-PCR results. Our results demonstrate that pediatric HCV infection is characterized by high viral loads and diverse HCV viremia patterns, independent of both age and route of transmission in the population under study. Further research is necessary to determine whether the high rate of HCV replication is related to virus variability or to host immune response.
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PMID:Hepatitis C virus infection in infants and children from Argentina. 1500 75

Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval [CI], 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline characteristics, plasma human immunodeficiency virus RNA levels of >or=5 log(10) copies/mL (hazard ratio [HR], 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1-1.2), creatinine clearance levels of <70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.
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PMID:Incidence of and risk factors for adverse drug reactions in a prospective cohort of HIV-infected adults initiating protease inhibitor-containing therapy. 1530 35

In 10% of the patients with chronic abnormal alanine aminotransferase (ALT) levels no cause is found. The prognosis of this liver disease, the increased risk of liver fibrosis regardless of the types of histological lesions and the need for a liver biopsy are unknown. Nearly 50% of these cases are explained by non-alcoholic steatohepatitis (NASH). The aim of this study was to evaluate, in patients with accidentally detected chronically elevated ALT levels, the prevalence of fibrosis and NASH, and the clinical and biological factors associated with each entity. Retrospectively, 67 patients (mean age, 46.6 +/- 12.1 years; 45 males) were included. All patients had a liver biopsy and were hepatitis B virus, hepatitis C virus, human immunodeficiency virus seronegative without alcohol, drug, autoimmune or genetically induced liver disease, with ALT > N (the upper limit of normal). NASH was evaluated according to necroinflammatory lesions and fibrosis. Fibrosis was evaluated according to the METAVIR score. Statistical analyses were performed using Student's t test, the Mann-Whitney rank-sum test and the chi-square test. Fibrosis scores were: F0, 37.3%; F1, 32.8%; F2, 26.9%; F3, 1.5%; and F4, 1.5%. NASH was absent in 59.7% and present in 40.3%. Significant differences were observed between F < 2 and F > or = 2 fibrosis patients for aspartate aminotransferase (AST) and ALT and between patients with NASH or without for body mass index. Overall, the risk of F > or = 2 fibrosis was increased in patients with AST > N, ALT > 2N or AST > N and ALT > 2N. The prevalence of F > or = 2 fibrosis and NASH in patients with unexplained chronic abnormal ALT are 30% and 40%, respectively. Since the risk of F > or = 2 fibrosis is significantly increased in patients with AST > N and/or ALT > 2N, liver biopsy should be performed only in patients with AST > N or ALT > 2N.
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PMID:Should a liver biopsy be done in patients with subclinical chronically elevated transaminases? 1531 12

To investigate whether infection with human immunodeficiency virus 1 (HIV-1) affects fibrosis development in patients infected with Schistosoma mansoni, we evaluated schistosomiasis-induced pathology in the livers of Kenyan patients co-infected with HIV-1. Compared with persons with schistosomiasis alone (n = 58), there were no significant differences in distribution of ultrasound-detectable pathology in persons with HIV-1 co-infection (n = 23). Similarly, serum aspartate aminotransferase levels were not significantly different in HIV-1+ individuals. Hepatic fibrosis was associated with significantly decreased CD4+ T cell counts, even in the absence of HIV-1 infection. These data suggest that HIV-1 co-infection does not significantly alter the proportion of patients experiencing schistosomiasis-induced fibrosis, but pathology associated with S. mansoni infections leads to CD4+ T cell reductions and thereby may exacerbate the effects of HIV-1 in co-infected individuals.
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PMID:Short report: Evaluation of hepatic fibrosis in persons co-infected with Schistosoma mansoni and human immunodeficiency virus 1. 1564 72

Human immunodeficiency virus (HIV)-infected South African patients (n=468) received blinded lamivudine or emtricitabine, stavudine, and either nevirapine or efavirenz (based on screening viral load). Baseline characteristics were analyzed in univariate and multivariate regression, to identify risk factors for hepatotoxicity (grade 3 or greater increase in serum aminotransferase levels). The occurrence of early hepatotoxicity was 17% in the nevirapine group and 0% in the efavirenz group and was balanced between the lamivudine and emtricitabine arms. Two subjects died of hepatic failure. Independent risk factors were body-mass index (BMI) <18.5, female sex, serum albumin level <35 g/L, mean corpuscular volume >85 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L. The use of nevirapine in female patients with a low BMI should be discouraged.
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PMID:Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects. 1599 71


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