Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.
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PMID:The value of liver function tests in hepatocellular carcinoma. 1087 29

Because in experimental hepatocarcinogenesis apoptosis increases from normal to preneoplastic to carcinoma tissue, proapoptotic factors, such as activin-A, may represent useful markers for hepatocellular carcinoma (HCC). In this study, serum activin-A was measured in 99 cirrhotic patients, of whom 55 had HCC. Activin-A concentrations were higher in HCC patients (median, 2.33 ng/ml; range, 0.41-8.12) than in patients with nonmalignant cirrhosis (1.28 ng/ml; range, 0.35-6.25) (P < .05). All 12 patients with activin-A greater than 3 ng/ml and serum alpha-fetoprotein greater than 30 ng/ml had HCC, in comparison to 32 of 41 patients who had only one and to 11 of 46 patients who had both markers below these cutoffs (P < .0001). No correlation was found between activin-A and alpha-fetoprotein in the two groups, whereas in patients with HCC, activin-A was strictly correlated with serum aspartate aminotransferase (P < .001). Activin-A mRNA for inhibin betaA subunit was expressed both in tumor and nontumor liver tissues in a case of HCC superimposed on cirrhosis and was not expressed in a case of HCC without cirrhosis. In conclusion, cirrhotic patients with HCC have high serum activin-A, to the production of which both the cirrhotic liver and the liver tumor are likely to contribute.
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PMID:Evaluation of circulating activin-A as a serum marker of hepatocellular carcinoma. 1091 35

Recent studies have shown that expression levels of the multidrug resistance gene MDR1, which encodes the drug transporter P-glycoprotein, correlate with prognostic outcomes of certain tumor types. These findings suggest that expression of MDR1 may affect tumor behaviors. To address this issue further, we investigated the expression of mdr1a, a human MDR1 homolog, on the development of hepatocellular carcinoma in a transgenic mouse model carrying the liver-targeted expression of human hepatitis-B virus (HBV) surface antigen. The pathogenetic program was compared in HBV mice carrying either mdr1a(+/+) or mdr1a(-/-). We found that the expressions of proliferative activity markers, Ki67 nuclear antigen, and proliferating cell nuclear antigen were elevated in mdr1a(-/-) mice younger than 10 wk in comparison with those in the same age group of wild-type animals. Replication in the hepatic population as determined by bromodeoxyuridine incorporation tended to support observation that mdr1a(-/-) mice exhibited elevated labeling indices in this age group. Moreover, histologic staining and flow-cytometric analysis showed that the mdr1a(-/-) animals exhibited a higher cell population with polyploidy than did the mdr1a(+/+) counterparts of the same age. However, no significant differences in the expression of the liver-injury markers serum alanine transaminase and aspartate transaminase were observed. Although our results showed that absence of mdr1a expression is correlated with modest enhanced proliferative characteristics in the livers at stage before the development of hepatocellular carcinoma, the overall life spans between these two strains of mice were not significantly different. The implication of these findings to the role of P-glycoprotein in tumor development and cancer chemotherapy is discussed.
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PMID:Elevated expression of hepatic proliferative markers during early hepatocarcinogenesis in hepatitis-B virus transgenic mice lacking mdr1a-encoded P-glycoprotein. 1107 7

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.
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PMID:Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. 1119 23

This study was undertaken to detect TTV DNA in serum samples from patients with non-A, non-B, non-C, non-E, and non-G (non-A-G) liver diseases and from blood donors, and to investigate the clinicopathological features of TTV infection including its prevalence and influence on liver disease. The study population consisted of 20 patients with non-A-G liver diseases (nine with chronic hepatitis (CH), six with liver cirrhosis (LC), and five with hepatocellular carcinoma (HCC), as well as 47 blood donors. Detection of TTV DNA was conducted with 200 &mgr;l of serum by the nested polymerase chain reaction. The detection rate of TTV DNA by subject category was CH 55.9; LC 66.7; HCC 60%; and blood donors 28%. Regarding blood biochemistry, TTV DNA-positive patients tended to show higher levels of aspartate aminotransferase and alanine aminotransferase, as well as lower levels of platelet counts. Long-term follow-up revealed that TTV DNA-positive patients exhibited characteristic, multiple peaks of alanine aminotransferase (ALT) levels. The histologic findings in the livers of TTV DNA-positive patients with CH consisted of moderate necro-inflammatory reactions. In conclusion, it is possible that the TTV genotype 1b infection caused liver injury.
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PMID:Clinicopathological features of serum TTV DNA-positive non-A-G liver diseases in Japan. 1155 37

In male C3H/He mice, which frequently develop spontaneous liver tumorigenesis, 5 wk of age and weighing about 20 g, the comparative effects on liver tumor incidence from the feeding of olive oil (OLI), safflower oil (SAF), and linseed oil (LIS) diets for 50 wk, the concentrations of total cholesterol (T-CHOL), triacylglycerol (TG), lipid peroxides in the plasma and liver, and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the plasma were examined. The changes in body weight and liver weight were not different among dietary groups. The number of mice bearing liver adenoma was greater in the SAF group than in the OLI and LIS groups. Liver carcinoma was observed in the SAF group, but not in the OLI and LIS groups. The concentrations of T-CHOL in the plasma and liver were higher in the OLI group than in the other groups. TG levels in the plasma and liver were highest in the OLI group and followed in order by the SAF and LIS groups. The concentration of plasma lipid peroxide was higher in the LIS group than in the other groups. Liver lipid peroxide content was extremely high in the LIS group, medium in the SAF group, and low in the OLI group. The activity of AST was highest in the OLI group and followed in order by the SAF and LIS groups. ALT activity was higher in the OLI group than in the other groups. A positive relationship between spontaneous liver tumorigenesis and the concentrations of T-CHOL, TG, and lipid peroxide or AST and ALT activities was hardly observed. These results suggested that spontaneous tumorigenesis in the liver of male C3H/He mice bred for 50 wk was suppressed by being supplied with OLI and LIS, compared with SAF, which had no direct relation to the concentrations of T-CHOL, TG, and lipid peroxide in the plasma and liver and the activities of plasma AST and ALT.
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PMID:Comparative effect of dietary olive, safflower, and linseed oils on spontaneous liver tumorigenesis in C3H/He mice. 1181 53

There has been a dramatic improvement in recent results of hepatectomy for hepatocellular carcinoma in cirrhotic patients. Hospital mortality rates of less than 5% are frequently reported. The improvement is largely a result of better techniques and performance of surgeons in hepatectomy, and reduction in blood loss and transfusion requirement. Better selection of patients is perhaps a more significant contributory factor. Careful identification of risk factors related to the medical condition of the patient, functional reserve of the liver and volume of the remnant liver is essential for the prevention of postoperative liver failure. Indocyanine green clearance test is the most accurate test for assessment of liver function reserve. An indocyanine green retention rate of 14% at 15 minutes is the safety limit for major hepatectomy for cirrhotic patients. A maximum of 60% of the nontumorous liver can be resected safely. Computed tomography is therefore an important assessment parameter. The liver function reserve also reveals the suitability for hepatectomy. Liver enzymes, alanine aminotransferase or aspartate aminotransferase can reflect the hepatic activity, which could be responsible for the impaired liver function. Steatosis is another factor that influences hepatic function reserve. Age is also an important risk factor in hepatectomy because elderly patients may harbor occult heart disease, reduced respiratory and liver function reserves. After recognizing the risk factors, surgeons should eliminate operative morbidity and mortality by making appropriate decisions based on the assessments. In conclusion, preoperative risk assessment involves evaluation of hepatic function reserve, remnant liver volume, liver status, age and the medical condition of the patient. A 0% hospital mortality rate is considered the objective.
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PMID:Methods and related drawbacks in the estimation of surgical risks in cirrhotic patients undergoing hepatectomy. 1194 45

Aflatoxin B(1) (AFB(1)) is a fungal toxin that causes both acute hepatotoxicity and hepatocellular carcinoma in humans and experimental animals. Previous studies demonstrated that a small, noninjurious dose of bacterial lipopolysaccharide (LPS) augments the hepatotoxicity of AFB(1) through activation of inflammatory cells and production of soluble inflammatory mediators (Barton et al., 2000b, 2001). This study was conducted to examine the effect of LPS on the dose-response relationship for AFB(1)-induced liver injury. Male Sprague-Dawley rats (250-350g) were treated with AFB(1) (0.1 mg/kg-6.3 mg/kg, ip) and 4 h later with a noninjurious dose of E. coli LPS (7.4 x 10(6) EU/kg, iv). Twenty-four h after AFB(1) administration, hepatic parenchymal cell injury was estimated from elevations in serum alanine aminotransferase and aspartate aminotransferase activities. Injury to intrahepatic bile ducts was evaluated from increased serum gamma-glutamyl transferase and alkaline phosphatase activities. Based on benchmark dose (BMD) analysis, the AFB(1) BMD for parenchymal cell injury was decreased 10-fold by LPS cotreatment, whereas AFB(1) BMDs for bile duct injury were decreased nearly 20-fold. The data suggest that concurrent inflammation renders the liver considerably more sensitive to the hepatotoxic effects of AFB(1).
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PMID:Bacterial lipopolysaccharide exposure alters aflatoxin B(1) hepatotoxicity: benchmark dose analysis for markers of liver injury. 1207 24

The relationship between the recurrence of hepatocellular carcinoma (HCC) and the degree of inflammation was evaluated in resected livers with the hepatitis C virus (HCV) -associated HCC. Seventy-three patients with HCV-associated HCC who were followed up for more than 2 years were selected for this study. In these cases, the degree of chronic hepatitis in noncancerous regions at the time of surgery was classified according to the New Inuyama Classification as follows, the degree of necroinflammatory activity (Grading) was graded from A0 to A3, and the degree of fibrosis (Staging) was staged on F0-F4. In addition, among these patients, 41 patients who were followed by blood tests every 3 months were divided into two groups (high or low group) according to annual average levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), the platelet counts (Plt), and alpha-fetoprotein (AFP). As a result, cancer-free survival rate was significantly lower in the high-grade group (A3) than in the low-grade group (A1 or 2) (P=0.01). The high ALT (>80 IU) group and the high AFP (>20 mg/ml) group also had significantly worse cancer-free survival rate than the low ALT group and the low AFP group (P=0.04 for ALT, P=0.03 for AFP). A multivariate analysis for the prognostic values revealed the AFP level (P=0.02) and the Grading (P=0.04) were useful as independent prognostic factors concerning recurrence. In conclusion, the degree of inflammatory activity (Grading) is considered to be a useful factor regarding recurrence after liver resection in patients with HCC. Furthermore, the inhibition of inflammation in remnant liver may also contribute to the prevention of recurrence.
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PMID:Relationship between the histological degrees of hepatitis and the postoperative recurrence of hepatocellular carcinoma in patients with hepatitis C. 1207 15

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.
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PMID:Therapeutic Options in Nonalcoholic Fatty Liver Disease. 1240 79


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