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)

As chronic liver disease progresses, an imbalance occurs between synthesis and breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs) prevent their fibrolytic action. In the present study, serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were investigated as non-invasive parameters for the diagnosis of hepatic fibrosis in patients with HCV related chronic liver disease. Their diagnostic potential was evaluated in comparison to hepatic histology and standard liver function tests. A sandwich enzyme immunoassay technique was used to study circulating values of MMP-2 and TIMP-1 in forty-one patients with HCV antibodies in their sera (27 patients with biopsy ascertained chronic hepatitis C and 14 patients with histologically proven liver cirrhosis. Hepatic histology was evaluated using the hepatitis-activity-index according to Ishak et al. (1995), quantifying separately inflammatory activity and fibrosis. Ten healthy individuals were also included in the study as controls. Serum levels of MMP-2 were similar in controls and in chronic hepatitis C patients with (n = 15) and without (n = 12) fibrosis, but increased significantly in cirrhosis. TIMP-1 serum values showed a steady increase from normal controls to chronic hepatitis C without fibrosis, hepatitis C with fibrosis, and cirrhosis. The diagnostic potential of MMP-2 to detect fibrosis was low with a sensitivity of 7% and a diagnostic efficiency of 56%. The diagnostic potential of circulating MMP-2 to detect cirrhosis was higher with a sensitivity of 83% and a specificity of 96% resulting in a diagnostic efficiency of 92%. Serum TIMP-1 values detected fibrosis with a sensitivity of 67% and a specificity of 69% resulting in an efficiency rate of 70%. TIMP-1 values detected cirrhosis with 100% sensitivity but only 75% specificity. The diagnostic potential of circulating TIMP-1 was higher than that of serum ALT, AST or albumin values. In conclusion, serum values of MMP-2 and TIMP-1 are able to detect cirrhosis with a high sensitivity. Moreover, TIMP-1 values can detect fibrosis with comparable efficiency. Regular determinations of both TIMP-1 and MMP-2 in patients with chronic hepatitis C may be used as indicators of increasing fibrosis and the development of cirrhosis.
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PMID:Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease. 1571 20

Serum biochemical liver tests (LTs) (ALT, AST, GGT) and platelet counts are often used to screen for chronic liver disease. Population-based data on abnormal LTs in Mediterranean areas are lacking. The prevalence and etiology of abnormal LTs were assessed from 2002 to 2003 in a 1 in 5 systematic random sample of the general population who were 12 years of age or older in Cittanova, a southern Italian town with 10,600 inhabitants. LTs, indices of metabolism, and markers of HBV and HCV infection were assayed and alcohol intake was recorded in the selected population. In virus-free individuals with abnormal LTs, LTs were retested, and upper abdominal echography and tests for other causes of liver damage were undertaken. Among the 1,645 individuals screened, the prevalence of anti-HCV was 6.5%; the prevalence was particularly high in individuals over 50 years of age. The corresponding prevalence for HBsAg was 0.8%. The overall prevalence of individuals with abnormal LTs was 12.7% (95% CI: 11.1-14.3). The probable cause of abnormal LTs was excessive alcohol in 45.6%, HCV in 18.6%, HBV in 1%, alcohol plus HCV and/or HBV in 8.8%, and rare diseases in 2%. In 24% of individuals with abnormal LTs, the probable cause was nonalcoholic fatty liver disease (NAFLD); in this subgroup, increased body weight, hypercholesterolemia, and hyperglycemia were common, and 63.3% of them had a bright liver at echography. In conclusion, in southern Italy, a Mediterranean area where dietary habits are different from those in industrialized areas, one eighth of the general population has abnormal LTs suggestive of possible liver damage; NAFLD appears to be emerging as a potentially important etiology of this presumed liver injury.
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PMID:Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town. 1584 64

Alpha1-antitrypsin deficiency (AATD) is a common hereditary disorder associated with high risk of developing pulmonary emphysema early in life and, to a lesser extent, chronic liver disease and cirrhosis. Among Northern Europeans and Northern Americans, more than 95% of individuals with emphysema associated with AATD carry the most frequent AAT deficient gene variants, PI*Z and PI*S. Rare AAT deficient variants account for 2-4% of AATD individuals. We extend the sequence data on AAT by characterizing a novel Null allele detected in 3 subjects: a carrier belonging to an Italian/Egyptian family and 2 members of a family originating from Southern Italy. The mutation raised on a M1 (Ala213) base allele and it is characterized by an A-->T transversion at exon III, nt 218, codon 259 (AAA-->TAA) (GeneBank accession number AY 256958). The transversion results in a premature stop codon (Lys259AAA-->Stop259TAA). The proposed nomenclature of Q0cairo is from the birthplace of the father of first recognized subject. Serum levels and isoelectric focusing of AAT were consistent with the presence of the Null variant.
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PMID:Identification of a novel alpha1-antitrypsin null variant (Q0Cairo). 1590 97

Childhood NAFLD has become an important childhood liver disease, and it is probably highly prevalent. The full of spectrum of NAFLD has been identified in children. It is not currently known whether or not simple hepatic steatosis in children is benign or whether it evolves to NASH over time. In contrast, childhood NASH certainly can have serious consequences. Cirrhosis is apparently rare in children with NAFLD, but it definitely occurs. Childhood NAFLD may occur in very young children, and there is no female predominance in the pediatric age bracket. Children present with vague abdominal pain, if they have any symptoms at all, but frequently hepatic steatosis is found incidentally on abdominal imaging. Laboratory studies show that serum aminotransferase abnormalities are rather moderate, with serum alanine aminotransferase (ALT) more elevated than serum aspartate aminotransferase (AST). Hypertriglyceridemia is the typical blood lipid abnormality, although hypercholesterolemia may occur. NASH may be more severe in children from certain ethnic groups, including Hispanics and Asians, or in association with certain metabolic disorders characterized by abnormalities in insulin receptor structure or signaling, such as lipodystrophy syndromes. Weight loss through dietary redesign and a regimen of regular exercise remains the mainstay for treatment for childhood NAFLD. A dietary strategy to minimize postprandial hyperinsulinemia and overall fat intake, such as a low glycemic index diet, may be the best dietary strategy. The real efficacy of drug treatments in children requires further investigation. The overriding message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.
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PMID:Non-alcoholic fatty liver disease (NAFLD) in children. 1597 Apr 96

Dimethylformaide (DMF) is a major solvent predominately used in synthetic leather and resin production. Many human and animal studies have linked the cause of hepatoxicity to DMF. Previously, the authors demonstrated the significant dose-response relationship between abnormal liver function tests and DMF exposure and the interaction with hepatitis B virus (HBV) infection in Taiwanese workers. Because the toxic effect of various chemicals can be modified by metabolic traits, the study also investigated the influence of the glutathione S-transferases (GSTM1 and GSTT1) on the toxic effect of DMF. The average DMF exposure concentration was 23.87 ppm (range 5.2-86.6 ppm) in the high-exposure (>/=5 ppm) group and 2.41 ppm (range 0.9-4.3 ppm) in the low-exposure (<5 ppm) group. There were 13 of 44 (29.6%) abnormal liver function tests (elevations of either glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT)) among the high DMF exposure workers, two of 22 (9.1%) abnormal liver function tests among the low DMF exposure workers. Chronic liver disease as determined by ultrasonography was present in seven of 44 (15.9%) high DMF exposure workers, and 0 of 22 (0%) low DMF exposure workers. There were 11 of 34 (32.4%) abnormal liver function tests among the GSTT1 null genotype workers, and four of 32 (12.5%) abnormal liver function tests among the GSTT1-positive genotype workers. Compared with the low DMF exposure workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 6.78 (0.94-48.7) for the high DMF exposure workers. Compared with the GSTT1-positive genotype workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 4.41 (1.15-16.9) for the GSTT1 null genotype workers. Compared with the low DMF group with GSTT1-positive genotype workers, the odds ratio (adjusted for HBV status) of abnormal liver function test was 12.38, 95% CI=(1.04-146.9) for the high DMF group with GSTT1 null genotype workers. This study indicates that abnormal liver function and chronic liver disease are associated with DMF exposure, and there are more than multiplicative interaction effects on abnormal liver function tests between the DMF exposure and the GSTT1 genotype.
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PMID:Abnormal liver function associated with occupational exposure to dimethylformamide and glutathione S-transferase polymorphisms. 1630 70

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that has been shown to progress to cirrhosis and hepatocellular carcinoma. This article reviews the prevalence of NAFLD and the factors associated this disorder, and with the more advanced stages of NAFLD, including nonalcoholic steatohepatitis (NASH) and fibrosis. In the general population, the estimated prevalence ranges from 3% to 24%, with most estimates in the 6% to 14% range. NAFLD is extremely common among patients undergoing bariatric surgery, ranging from 84% to 96%. In these patients, 25% to 55% have NASH, 34% to 47% have fibrosis, and 2% to 12% have bridging fibrosis or cirrhosis. NAFLD appears to be most strongly associated with obesity, and insulin resistance states including diabetes and with other features of the metabolic syndrome, such as high triglycerides and low HDL. It appears to be more common in men, and it increases with increasing age and after menopause. Some data suggest that Mexican Americans are more likely to have NAFLD and blacks are less likely compared with non-Hispanic whites. More advanced stages of NAFLD are associated with older age, higher body mass index, diabetes, hypertension, high triglycerides, and/or insulin resistance. An AST/ALT ratio greater >1 may also indicate more severe disease. Although hepatocellular carcinoma can occur in the setting of NAFLD, the risk factors for hepatocellular carcinoma in the setting of NAFLD have not been established. More prospective studies are needed to determine the true risk factors for the development and progression of NAFLD to help identify patients at highest risk who might benefit from treatment trials.
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PMID:The epidemiology of nonalcoholic fatty liver disease in adults. 1654 Jul 68

Many Koreans, in addition to Japanese, were killed or injured by the atomic bombs detonated over Hiroshima and Nagasaki, Japan, in 1945. Our study examined noncancer diseases of Korean A-bomb survivors in residence at Hapcheon, Republic of Korea and evaluated whether they had significantly higher prevalence of noncancer diseases than non-exposed people. We evaluated a number of tests, including anthropometric measurements, blood pressure, blood chemistry, hepatitis B surface antigen, and urinalysis, of survivors (n=223) and controls (n=372). Univariate analysis revealed significantly lower fasting glucose and creatinine, and higher diastolic blood pressure, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen levels in the survivors than in the controls. The calculation of crude prevalence ratios (PRs) revealed that A-bomb survivors had a significantly higher prevalence of hypertension (PR, 1.16; 95% CI, 1.00-1.35) and chronic liver disease (2.20; 1.59-3.06) than controls. After adjusting for covariates (age, sex, body mass index, marital status, education, alcohol consumption, and smoking), A-bomb survivors had a significantly higher prevalence of hypertension (1.24; 1.06-1.44), chronic liver disease (2.07; 1.51-2.84), and hypercholesterolemia (1.79; 1.11-2.90) than controls. This study suggests that A-bomb exposure is associated with a higher prevalence of non-cancer diseases in Korean survivors.
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PMID:Non-cancer diseases of Korean atomic bomb survivors in residence at Hapcheon, Republic of Korea. 1677 77

An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty-six children (9 girls, 17 boys; mean age, 7.66 +/- 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilson's disease in one, and alpha-1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 +/- 3.49 yr, which was significantly lower than in those without UTI (9.75 +/- 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60%) patients with UTI. VCUG demonstrated vesicoureteral reflux in two patients. In conclusion, symptomatic UTI is common in children with cirrhosis. It occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease. In febrile children with chronic liver disease, UTI should be considered in the differential diagnosis.
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PMID:Frequency of urinary tract infection in pediatric liver transplantation candidates. 1749 20

Non-ceruloplasmin bound copper ('free') seems slightly elevated in Alzheimer's disease (AD) patients. To test the hypothesis of a correlation between 'free' copper and liver function in AD. We evaluated 51 AD patients and 53 controls through typical tests for chronic liver disease (AST, ALT, gamma-GT, Albumin, prothrombin time - PT-, bilirubins), along with copper, ceruloplasmin, iron, cholesterol in the serum and apolipoprotein E epsilon4 (APOE4) genotype. Absolute serum copper and 'free' copper were higher, albumin was lower and PT longer in AD patients than in controls. 'Free' copper correlated negatively with markers of liver function, in that albumin and albumin/PT ratio (r = -0.43, p = 0.004), and positively with direct bilirubin. Copper and 'free' copper were higher in the APOE4 carriers. These results suggest that abnormalities in copper metabolism might have an effect on liver function in AD.
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PMID:'Free' copper in serum of Alzheimer's disease patients correlates with markers of liver function. 1764 16

Adiponectin possesses anti-inflammatory, insulin-sensitizing and anti-atherosclerotic properties. The aim of this study was to assess the levels of serum adiponectin in patients with chronic viral hepatitis C and B and correlate them with parameters exploring insulin resistance and indices of chronic liver disease. Seventy-two patients with chronic hepatitis C virus (HCV) infection and 73 patients with chronic hepatitis B virus (HBV) infection, matched for age and sex, were studied. All individuals were examined for serum concentrations of adiponectin, insulin, C-peptide and homeostasis model assessment for insulin resistance (HOMA-IR). Viral parameters and liver histology were also evaluated. Serum adiponectin levels were significantly higher in HCV compared with HBV-infected patients. Correlation analysis in the whole group demonstrated that serum adiponectin was positively correlated with aspartate aminotransferase, alkaline phosphatase, globulins, high-density lipoprotein cholesterol and staging score, while it was negatively correlated with body mass index, insulin, C-peptide and HOMA-IR. Logistic regression analysis identified type of infection (HCV vs HBV), alcohol consumption more than 25 g daily, serum total globulin and low C-peptide as significant predictive variables associated with high adiponectin levels. Higher levels of serum adiponectin in HCV compared with HBV patients could have a role in the slower disease progression of chronic HCV infection. In addition, alcohol intake more than 25 g daily seems to be a significant predictor for hyperadiponectinaemia in patients with chronic viral hepatitis C or B. Finally, in this study, a clear positive association between adiponectin and hepatic necroinflammation or staging score was not found.
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PMID:Serum adiponectin in chronic hepatitis C and B. 1765 Feb 92


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