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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver damage influenced by alcohol is already associated with the development of a portal hypertension at an early stage. With the aid of laparoscopic transhepatic manometry we determined the pressure levels in the branches of the portal and hepatic veins in 15 patients (16 examinations) comprising 14 men and 1 women, with alcoholic toxic liver damage. It was shown that already with alcoholic parenchymal damage associated with portal and centrolobular fibrosis, a portal hypertension is initiated, the greatest manifestation of which is found in the group with histological changes taking the form of a remodelling (distorsion of architecture) or cirrhosis. The level of alcohol consumption has no direct influence on the level of pressure in the vascular systems investigated. Ther is, however, a correlation between the level of alcohol consumption, extent of fibrosis and portal hypertension. For the clinico-chemical parameters investigated (Gamma-glob., GOT, GPT, GLDH, gamma-GT, alkaline phosphatase, bilirubin) no significant differences were found dependent on the level of alcohol consumption or the degree of fibrosis.
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PMID:Laparoscopic transhepatic manometry in portal hypertension in patients with alcoholic liver damage. 645 14

Three patients out of 16 with chronic active hepatitis exhibited villous atrophy in biopsy specimens from the upper jejunum. These patients were put on a gluten-free diet for one year, and the intestinal changes normalized in two of the patients, but did not heal in the third patient. The levels of alanine aminotransferase and IgG, did not decrease under the gluten-free diet. The liver disease of the patients with intestinal changes ran a serious course: one patient died in hepatic coma, and one patient developed portal hypertension with recurring hematemesis. These complications did not appear in the patients with healthy intestine. It is suggested that the three patients suffered from both chronic active hepatitis and coeliac disease, which appeared concomitantly on the basis of a genetic disposition for both diseases.
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PMID:Gluten-free diet in chronic active hepatitis associated with intestinal villous atrophy. 708 83

Autoimmune chronic active hepatitis (CAH-A) is a chronic liver disease of unknown etiology that is believed to have an autoimmune pathogenesis. The disease is slowly progressive until hepatic failure and portal hypertension develop and either death or liver transplantation occur. Currently, the only widely recognized therapy is the administration of glucocorticoids, which have both anti-inflammatory and immunosuppressive actions. Many patients cannot tolerate such therapy because of the psychiatric, osteoporotic, and weight-enhancing actions of steroids. Tacrolimus (FK 506) is a new macrolide antibiotic that has an immunosuppressive activity that is estimated to be 10-200 times greater than that of cyclosporine. Because of its greater immunosuppressive activity, we have used it in the treatment of 21 patients with autoimmune chronic active hepatitis. Before each subject was treated, a liver biopsy and a panel of hematological, serological, and biochemical parameters were assessed. The Tacrolimus was administered orally at 12-h intervals, and the dose was controlled by monitoring plasma FK trough levels. After 3 months of therapy at an oral dose of 3 mg twice a day, having achieved a median blood level of 0.5 ng/ml, the serum ALT level was reduced by 80%, and the AST level was reduced by 70%. Modest change in the white blood cell count and platelet count were noted. The median BUN level increased from a level of 12 to 18 mg/dl, and the serum creatinine increased from 0.9 to 1.3 mg/dl. These preliminary data demonstrate that: 1) Tacrolimus can be used to successfully treat CAH-A; 2) the response of CAH-A to Tacrolimus treatment is rapid and sustained; and 3) a minor increase in the serum BUN and creatinine levels occurs as a consequence of Tacrolimus treatment. It is anticipated that with continued treatment for periods of 1-2 yr, the natural history of CAH-A will be changed such that hepatic failure and the requirement for liver transplantation may be averted.
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PMID:Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. 753 44

Veno-occlusive disease (VOD) of the liver is a major complication of bone marrow transplantation. The clinical features are those of intrahepatic portal hypertension and while the reported frequency varies considerably, severe disease is readily identifiable and is associated with a high mortality. The single most important risk factor for the development of VOD is an elevated ALT prior to transplantation. The incidence of VOD may be reduced by prophylactic administration of anticoagulant or antiplatelet drugs and established disease can be treated by thrombolytic therapy with tissue plasminogen activator. These observations suggest that endothelial damage and thrombin generation are fundamental to the disease process. Protection of the endothelium from toxic damage and inhibition of thrombin generation are potential targets for preventing VOD.
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PMID:Veno-occlusive disease of the liver complicating bone marrow transplantation. 801 44

We measured plasma endothelin-1 (ET-1) concentrations in 20 healthy controls and 63 patients with liver diseases including 9 cases of acute hepatitis (AH), 14 cases of chronic hepatitis (CH), 24 cases of liver cirrhosis (LC), 11 cases of hepatocellular carcinoma with LC (HCC), 3 of primary biliary cirrhosis and 2 of idiopathic portal hypertension. ET-1 levels in AH (5.07 +/- 2.54 pg/ml, mean +/- SD), LC (3.71 +/- 1.17) and HCC (3.08 +/- 0.93) were significantly higher than those in healthy controls (2.18 +/- 0.37). ET-1 levels in AH, LC and HCC were also significantly higher than those in CH (2.05 +/- 0.61). ET-1 levels showed negative correlations with serum albumin levels and Ch-Ease activities, and positive correlations with serum bilirubin levels, AST and ALT activities. However, there was no correlation between plasma ET-1 concentrations and concentrations of serum thrombomodulin which is known to be a marker of injured vascular endothelial cells. In cirrhotic patients, ET-1 levels were significantly influenced by the presence of ascites. The results of the present study suggest that plasma ET-1 concentrations may be a useful clinical indicator for use in the follow-up of patients with chronic liver diseases, e.g., progression from CH to LC, and change in grade of portal hypertension and decompensation in LC.
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PMID:Plasma endothelin-1 concentrations are elevated in acute hepatitis and liver cirrhosis but not in chronic hepatitis. 822 17

Laminin, a glycoprotein synthesised by Ito cells, has been considered a marker of fibrogenesis. The behaviour of laminin and clinical and laboratory data in 83 patients with cirrhosis were studied to find the factors associated with increases in this glycoprotein. There were increased concentrations of laminin in 62.7% of the patients (40% of the Child's A, 64.5% of the Child's B, and 75% of the Child's C categories). Significant differences in laminin concentrations were found between the Child's grades (p = 0.009) and between patients and controls (p < 0.0001). Correlations were found between laminin concentrations and mean corpuscular volume, aspartate aminotransferase, aspartate aminotransferase: alanine aminotransferase ratio, alkaline phosphatase activity, bilirubin and glycocholic acid concentrations, and hypoalbuminaemia--that is, variables related to liver insufficiency and alcohol intake. Moreover, patients with an alcohol intake higher than 100 g/day had higher laminin concentrations than those with a lower intake (p = 0.03). Conversely, there was no significant association with portal hypertension. Multivariate analysis showed that mean corpuscular volume, bilirubin concentrations, and hypoalbuminaemia were independently associated with laminin concentrations. Poor degradation associated with liver insufficiency seems to play an important part in the increase in serum laminin concentrations in these patients.
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PMID:Serum concentrations of laminin in cirrhosis of the liver. 834 86

Ribavirin in a fixed doses of 1.0 g/day was administered to 15 cirrhotic patients with portal hypertension and HCV-RNA detected in the blood by PCR during a six months period, in a non-controlled study. Two patients presented complications due to hepatic insufficiency and their data were not available at the end of the study. In four patients the hemoglobin levels fell below 20% of the initial value and in one the ribavirin dose had to be reduced. No other significant adverse reaction to the drug was observed. Almost all patients experienced a decrease in the aminotransferases levels during the study, specially in the first three months of treatment when the AST and ALT levels were significantly reduced when compared with the initial values. At the end of six months, four patients presented a complete response with normal aminotransferases levels, but only in one patient the HCV-RNA was not detected in the blood. In this patient the drug interruption was followed by elevation in aminotransferases levels and HCV-RNA detection in the blood 45 days later. Such results suggest that although well tolerated and inducing a transient decrease in AST and ALT, ribavirin alone administration is not able to erradicate virus C infection in patients with hepatic cirrhosis and portal hypertension.
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PMID:[Ribavirin in the treatment of hepatic cirrhosis due to hepatitis C virus. A non-controlled study]. 872 83

Gall-bladder wall thickening is commonly seen in patients with cirrhosis, but its exact causes have not been well established. We evaluated clinical, biochemical and haemodynamic data of patients with cirrhosis with respect to the presence of thickening of the gall-bladder wall. After excluding patients who presented with gallstones, acute or chronic cholecystitis, heart failure, a serum creatinine level greater than 2 mg/dL and/or a serum alanine aminotransferase level greater than 400 U/L, 77 patients with cirrhosis (75 male, two female; mean age 58 +/- 8 years) were enrolled in the study. Clinical, biochemical, ultrasound and haemodynamic data were obtained in every patient. Forty-one (53%) of 77 patients with cirrhosis had gall-bladder wall thickening (> 4 mm). Compared with patients with a normal gall-bladder wall, patients with gall-bladder wall thickening had significantly lower serum albumin levels (3.6 +/- 0.6 vs 2.9 +/- 0.7 gm/dL, respectively; P < 0.05), a longer prothrombin time (13 +/- 6 vs 16 +/- 6 s, respectively; P < 0.05), more patients with Child-Pugh class C (6 vs 37%, respectively; P < 0.05) and more patients with ascites (8 vs 50%, respectively; P < 0.05). In addition, compared with patients with a normal gall-bladder wall, those patients with gall-bladder wall thickening had a higher hepatic venous pressure gradient (13.9 +/- 4.5 vs 17.1 +/- 4.1 mmHg, respectively; P < 0.01) and a lower systemic vascular resistance (SVR; 1144 +/- 332 vs 1010 +/- 318 dyn.s/cm5, respectively; P < 0.05). Using a multivariate analysis, the presence of ascites and SVR lower than 900 dyn.s/cm5 were independently correlated with the presence of gall-bladder wall thickening, while a hepatic vein pressure gradient greater than 10 mmHg had only a marginally significant association. The presence of ascites, decreased SVR and portal hypertension are related to the occurrence of gall-bladder wall thickening in patients with cirrhosis, indicating that the development of gall-bladder wall thickening may be multifactorial.
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PMID:Gall-bladder wall thickening in patients with liver cirrhosis. 919 2

Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of which leads to liver damage.
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PMID:The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function. 924 25

The histopathology and clinical picture of hepatocellular carcinoma (HCC) varies between individual patients and regions. These variations are perhaps due to differences in the genetic alterations that precede hepatocarcinogenesis. In this study, the clinicopathological features of HCC were compared between southern African blacks and Japanese, indicating large differences in the frequency of underlying cirrhosis, grade of cancer cell differentiation and clinical course. Intra-abdominal bleeding and febrile, rapidly progressive HCC are more common among blacks. Such a difference is accounted for, in part, by frequent encapsulation of the tumour which is well differentiated, and grows slowly in an expanding fashion in Japan. Encapsulated HCC was not seen among the black patients studied. Other distinct clinicopathological types discussed in this paper include diffuse-type HCC which is usually caused by multiple portal spread occurring almost simultaneously; the clinical course is fulminant. Sclerosing carcinoma is frequently associated with hypercalcaemia in the United States, but not in Japan. Fibrolamellar carcinoma is nearly non-existent in Asia, whereas it is common among young adults in the West. Its prognosis is generally better than ordinary HCC. Hepatocellular carcinoma has a strong propensity to invade vessel and duct systems. Portal invasion does not produce distinct clinical signs although it may aggravate portal hypertension. Patients with tumour occlusion in the major portal vein may give rise to ischaemic hepatitis when blood pressure drops suddenly in the preterminal stage. Liver parenchyma develops submassive necrosis and clinically there is an acute rise in alanine aminotransferase (ALT). Invasion into a major hepatic vein and the inferior vena cava also occurs, but less frequently compared with portal invasion. The patient can live even with a tumour thrombus in the atrium crossing the tricuspid valves. Intraductal invasion causes acute jaundice as well as an occasional haemobilia with pain. We recently found that a distinct pathological type called 'extrahepatic growth' or 'pedunculated HCC' develops as a result of fusion of right-sided adrenal metastasis of HCC and the liver, perhaps through the 'adreno-hepatic fusion' which is rather common in cirrhotic livers.
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PMID:Hepatocellular carcinoma: clinicopathological aspects. 940 52


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