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

The inbred mutant strains of Long-Evans Cinnamon (LEC) rats spontaneously develops acute hepatitis as a result of abnormal copper accumulation, followed by chronic hepatitis, cholangiofibrosis and hepatocellular carcinoma. To shed some light on the role of macrophages in the liver failure, immunohistochemical methods were used to investigate the kinetics of macrophage populations in the liver of male LEC rats, in relation to the appearance of myofibroblastic cells and hepatocyte apoptosis. Rats examined at 24 weeks of age and moribund rats killed at 22-25 weeks of age had increased serum concentrations of aspartate aminotransferase and alanine aminotransferase, with jaundice and histological changes indicative of hepatic failure, whereas rats examined at 8, 12, 16 or 20 weeks old showed no such abnormal findings. Immunolabelling with ED1 (a monoclonal antibody recognizing rat macrophages) and ED2 (a monoclonal antibody specific for rat resident macrophages) revealed that numbers of blood monocyte-derived macrophages and Kupffer cells began to increase markedly at 16 weeks of age (before the onset of hepatitis). However, alpha-smooth muscle actin (SMA)-positive myofibroblastic cells (modulated perisinusoidal cells) and hepatocyte apoptosis, demonstrable by the TUNEL method, were rarely seen at 8, 12, 16, 20 or 24 weeks. There was no close relationship between macrophage expansion and the appearance of myofibroblastic cells or hepatocyte apoptosis. In moribund rats, only a few SMA-positive cells were seen in the periportal zones; hepatocytes undergoing apoptosis increased in number, and macrophages engulfing apoptotic bodies were observed occasionally, suggesting that apoptosis was related to hepatic failure as an early event. In addition, immunohistochemical examination demonstrated abnormal deposits of laminin along the sinusoids from 20 weeks, as an initial extracellular matrix protein in LEC rat livers.
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PMID:Macrophage populations and apoptotic cells in the liver before spontaneous hepatitis in Long-Evans Cinnamon (LEC) rats. 1020 30

Interferon-gamma (IFN-gamma) transgenic mice strongly express IFN-gamma in the liver and develop chronic hepatitis. Furthermore, hepatocyte apoptosis was shown by the TdT-mediated dUTP-biotin nick endlabeling method. In the present study, interleukin-1beta-converting enzyme (ICE) and CPP32-like protease activities in the liver of IFN-gamma transgenic mice were measured, using the synthetic substrates Ac-YVAD-MCA and Ac-DEVD-MCA. Plasma aspartate aminotransferase and alanine aminotransferase activities as well as CPP32-like activity were significantly elevated, while ICE activity was significantly reduced. The addition of the ICE inhibitor Ac-YVAD-CHO to IFN-gamma transgenic mouse liver cell cytosol had no effect on the CPP32 activity, in contrast to a CPP32 inhibitor. The present results indicate that chronic hepatitis in the IFN-gamma transgenic mouse is associated with a decrease in ICE and induction of CPP32-like activity.
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PMID:Chronic hepatitis in interferon-gamma transgenic mice is associated with elevated CPP32-like activity and interleukin-1beta-converting enzyme activity suppression. 1023 Aug 56

In Asians from the Pacific rim countries, alcohol sensitivity has been attributed mainly to a highly prevalent polymorphism in low Km aldehyde dehydrogenase (ALDH2). Chronic alcohol abuse may accelerate or aggravate the liver injury in chronic hepatitis C virus (HCV)-infected subjects. In this study, we examined the relationships among alcohol intake, ALDH2 genotypes, and liver injury in a high HCV-prevalent Japanese native island population. The ALDH2 genotypes are significantly associated with drinking habits. In HCV RNA positive subjects, serum alanine aminotransferase (ALT), as well as aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT), were significantly higher in habitual drinkers than in nonhabitual drinkers. In male habitual drinkers, the ALDH2*1/*1 subjects had higher liver necroinflammatory scores than the ALDH2*1/*2 subjects in all groups classified as: I, anti-HCV-seronegative; II, anti-HCV-seropositive with negative HCV RNA; and III, HCV RNA positive, although scores for the latter two groups were not statistically significant because of limited sample size. It was suggested that the liver function might be affected by the interaction between the ALDH2 genotypes and alcohol intake. These findings indicate that HCV-infected ALDH2*1/*1 habitual drinkers are the major target for the prevention of alcoholic liver diseases.
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PMID:Effects of alcohol intake and low Km aldehyde dehydrogenase on hepatic function in a high hepatitis C virus-prevalent Japanese island population. 1023 13

At routine determination of serum activities of transaminases (aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased levels are frequently found. An algorithm may be used in the analysis of elevated transaminase levels: after elimination of the most frequent causes of hepatitis (alcoholic hepatitis, chronic hepatitis B and C) and some rare conditions (autoimmune hepatitis, alpha 1-antitrypsin deficiency, haemochromatosis and Wilson's disease), the diagnosis will often be nonalcoholic steatohepatitis. Although nonalcoholic steatohepatitis is considered a stable disease, recent literature shows a progression to cirrhosis in 8-17%. So far, no effective therapeutic strategies are available for nonalcoholic steatohepatitis.
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PMID:[Management of asymptomatic elevated serum aminotransferase levels, particularly in nonalcoholic steatohepatitis]. 1032 Dec 58

Thirty consecutive, major liver resections performed with total vascular exclusion in both non-cirrhotic and cirrhotic patients were analysed retrospectively. The patients' ages ranged from 6 months to 80 years. Ten were Asians and five had cirrhosis associated with chronic hepatitis B or C. There was no perioperative death and the mean hospital stay was 6 days for adults and 9.2 days for children. The average vascular exclusion or warm ischaemia time was 25 min (range 10-55 min) and the average intraoperative blood volume given was 275 mL (range 0-3000 mL) packed red blood cells. Sixty per cent required no intraoperative blood transfusion. The mean total bilirubin and aspartate aminotransferase were 1.0 mg/dL (range 0.3-2.3 mg/dL) and 84 IU/L (range 14-306 IU/L) when measured prior to discharge at postoperative day 4-7. In our experience, total vascular exclusion is invaluable in major or difficult liver resections, especially lesions adjacent to the hepatic veins and vena cava. It is associated with a low blood transfusion requirement and a low incidence of complications. It further obviates the need for dissection of the porta hepatis and its associated risks. Total vascular exclusion time of 30 min appears to be well tolerated, even in patients with compensated cirrhosis.
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PMID:Major hepatic resection without blood transfusion: experience with total vascular exclusion. 1038 35

The ratio of serum aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) has been proposed as a noninvasive method of assessing liver fibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosing cirrhosis noninvasively as well as to verify the existence of a relationship between the ratio and liver functional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) were retrospectively evaluated and the AST/ALT ratio was related to monoethyl glycine xylidide (MEGX) formation. Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio and indocyanine green clearance and half-life. The AST/ALT ratio was able to separate patients with mild fibrosis from those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity, and platelet count were selected by multivariate analysis as variables associated with cirrhosis. The AST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine green clearance and half-life. The alterations of indocyanine green kinetics, which depend upon liver blood flow and uptake, were likely due to progressive fibrosis. These findings might partially explain the increase in the AST/ALT ratio as disease progresses.
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PMID:Progressive liver functional impairment is associated with an increase in AST/ALT ratio. 1038 5

To develop prognostic models for identifying children with hepatitis B who are likely to respond to interferon-alpha (IFN-alpha) or to spontaneously seroconvert, we evaluated results of a multinational controlled trial comprising 70 children with chronic hepatitis B who received IFN-alpha and 74 children who did not receive therapy. Prognostic models were developed using SMILES (similarity of least squares), which is a data analysis network that incorporates multidimensional relationships in the clinical data of complex diseases. Commonly collected clinical data included age, gender, serum aminotransferase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hepatitis B virus (HBV) DNA levels, and IFN-alpha dose. Additional data included pretreatment directional information (e.g. increases or decreases in serum aminotransferase and HBV DNA levels), liver biopsy results, race and transmission mode. Using data available prior to initiation of treatment, the SMILES models achieved prospective predictions of 89% for responders, 96% for non-responders, 100% for seroconverters and 93% for non-seroconverters. Although not predictive by themselves, the variables that had the greatest impact on predictions for IFN-alpha response were HBV DNA pretreatment direction, baseline HBV DNA, IFN-alpha dose and gender. The variables that had the greatest impact on predictions for spontaneous seroconversion were ALT pretreatment direction, baseline HBV DNA level, age and AST pretreatment direction. Therefore, these models may be useful in determining, in children with hepatitis B, the likelihood of response to IFN-alpha and spontaneous seroconversion.
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PMID:Statistical models for predicting response to interferon-alpha and spontaneous seroconversion in children with chronic hepatitis B. 1076 45

Resistance formation is a major problem in antiviral treatment of hepatitis B recurrence after liver transplantation. One possible therapeutic approach is an antiviral combination therapy with synergistic drugs. Four patients who were transplanted for chronic hepatitis B were analyzed retrospectively. All patients had reinfection of the graft and breakthrough of hepatitis B virus (HBV) during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy of lamivudine and interferon alpha 2a (3 times 3 million units weekly) was initiated. Addition of interferon markedly reduced viral replication rate in all patients. Three patients became HBV-DNA negative despite lamivudine resistance, but only two had a sustained response. No patient seroconverted to anti-HBe or lost HBsAg, but all patients showed a normalization of alanine aminotransferase and aspartate aminotransferase levels. No severe complications, and especially no rejection episodes occurred. Therefore lamivudine combined with interferon might be used for the therapy of hepatitis B reinfection after liver transplantation.
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PMID:Additional interferon alpha for lamivudine resistant hepatitis B infection after liver transplantation: a preliminary report. 1083 94

Background: Alanine aminotransferase (ALT) is frequently used as the sole biochemical marker for chronic hepatitis C (CHC), however, its value may be normal in cases with active disease. Recently, aspartate aminotransferase (AST) has been suggested as a useful predictor of liver pathology and conflicting results were obtained by using AST/ALT ratio to predict cirrhosis. Aims: To evaluate clinical utility of serum ALT and AST in CHC. Methods: The charts of 133 patients with CHC, whose ALT and AST were simultaneously tested from 1994 to 1996, were reviewed. ALT and AST were analyzed for both the entire cohort of patients and subgroups stratified for histopathology, age, gender, alcohol consumption, and risk factors of transmission. In 53 patients, the AST/ALT ratio was evaluated during interferon treatment. Results: The elevation of ALT significantly correlated with that of AST (r=0.79). The AST/ALT ratio increased with liver histological progression. The ratio >/=1 was predominantly in cirrhotic patients. During treatment the ratio increased. The AST remained elevated in eight of the 33 patients in whom the ALT had returned to normal during and after treatment. Conclusions: Both ALT and AST are useful markers for CHC. However, the AST may elevate alone, suggesting that measuring AST may be useful when the ALT is consistently normal. The AST/ALT ratio varies in different patients but increases with histological progression of fibrosis. An AST/ALT ratio >/=1 is highly suggestive of the presence of cirrhosis.
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PMID:An assessment of the clinical utility of serum ALT and AST in chronic hepatitis C. 1083 37

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


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