Liver enzymes aminotransferases

Liver In a retrospective review of 200 adult and pediatric recipients of hemopoietic stem cell transplants who took more than two consecutive doses of voriconazole, clinical hepatotoxicity was defined as any rises in liver enzymes (aminotransferases and alkaline phosphatase) that led to withdrawal of voriconazole and biochemical hepatotoxicity as a rise in one or more liver enz5nnes to more than three times the upper limit of the reference range or more than three times the baseline value if abnormal at... 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

Tolcapone has been associated with several cases of severe liver failure, including fatalities, and has been removed from the market in some countries. Thus, it should only be used in patients who cannot take or do not respond to entacapone. Serum alanine aminotransferase and aspartate aminotransferase concentrations should be monitored at baseline, then every 2 to 4 weeks for 6 months, and then periodically for the remainder of therapy. Patients who fail to show symptomatic benefit after 3 weeks should discontinue tolcapone. Entacapone has not been associated with liver damage, so monitoring of liver enzymes is not currently recommended.24,25,29... 

Elevated activities of liver enzymes (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase) were found in the serum of rats exposed continuously to 26 ppm phenol vapor for 15 days (Dalin and Kristoffersson 1974). Increased concentration of these enzymes in serum is often associated with liver injury but is not conclusive evidence for the type or severity of injury. Therefore, 26 ppm can be considered a less serious LOAEL in rats. Serum levels of... 

Hepatic Effects. Two days after a man was splashed with a phenol-water solution over his face, chest wall, hand, and both arms, serum bilirubin increased 2-fold (Horch et al. 1994). After 5 days, serum bilirubin returned to normal. An enlarged and tender liver and increased liver enzymes in the serum were reported in a case of chronic phenol poisoning (Merliss 1972). Lactate dehydrogenase was about 2-fold greater than normal, aspartate aminotransferase was about 21-fold greater than normal, and alanine aminotransferase was about 100-fold greater than normal. The man worked in a laboratory for 13.5 years where he distilled phenol several times a day. During the process, heavy odors were detectable, phenol was often spilled on his clothes, and he noted skin irritation. 

Both muscle and liver have aminotransferases, which, unlike deaminases, do not release the amino groups as free ammonium ion. This class of enzymes transfers the amino group from one carbon skeleton (an amino acid) to another (usually a-ketoglutarate, a citric acid cycle intermediate). Pyridoxal phosphate (PLP) derived from vitamin is required to mediate the transfer. 

Hepatomegaly, jaundice, and altered liver function tests have been reported in accidental poisonings with DME An outbreak of toxic liver disease was associated with DME exposure at a fabric coating factory. Thirty-six of 58 workers had elevations of either aspartate aminotransferase or alanine aminotransferase. Serological tests excluded known infectious causes of hepatitis in all but two cases. After modification of work practices and removal of the most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms occurred in most patients. Medical surveillance of the working population for 14 months revealed no further cases of toxic liver... 

ALL acute lymphocytic leukemia ALS amyotrophic lateral sclerosis ALT alanine aminotransferase (a liver enzyme)... 

E. Therapeutic response A randomized trial compared treatment with PEG-Intron, once weekly, to treatment with Intron A (interferon alfa-2b), three times weekly, in 1219 previously untreated adults with chronic hepatitis from HCV infection. Patients were treated for 48 weeks. Response to treatment was defined as undetectable HCV RNA (less than 100 copies per ml) and normalization of the liver enzyme alanine aminotransferase (ALT) at 24 weeks post-treatment. Response rates to the l.Opg/kg PEG-Intron doses and to Intron A were 24% and 12%. Patients receiving PEG-Intron with viral genotype 1 had a response rate of 14%, while patients with other viral genotypes had a 45% response rate. 

Liver Blood tests Liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, lactate dehydrogenase)... 

Hepatic Clearance Patients with significant hepatic dysfunction would be expected to have a decreased ability to metabolize or clear drugs. An increase in liver enzymes (aspartate aminotransferase [ASTI, alanine aminotransferase [ALT], and alkaline phosphatase [AlkPhos]) or an increase in bilirubin, prothrombin time and a decrease in serum albumin usually indicates hepatic dysfunction. 

ALT alanine aminotransferase AST aspartate aminotransferase CYP cytochrome P450 liver enzyme system NAPQI V-acetyl-p-benzoquinone imine NAT2 N-acetyltransferase 2 genotype... 

Elevated liver enzymes may occur in up to 15% of patients cirrhosis is rare. Liver function tests, aspartate aminotransferase (AST) or alanine aminotransferase (ALT), should be performed periodically. Methotrexate should be discontinued if these test values show sustained results greater than twice the upper limits of normal. Serum albumin levels also should be checked periodically, as signs of liver toxicity in some patients may not have liver inflammation manifested by AST or ALT elevation. Liver biopsy is now recommended before beginning methotrexate therapy only for patients with a history of excessive alcohol use, ongoing hepatitis B or C infection, or recurring elevation of AST. Biopsies during methotrexate therapy are recommended only for patients who develop consistently abnormal liver function tests. ... 

Coxibs and NSAIDs uncommonly cause drug-induced hepatitis the two NSAIDs most frequently implicated are diclofenac and sulin-dac. Patient monitoring should include periodic liver enzymes (aspartate aminotransferase and alanine aminotransferase), with cessation of therapy if these values exceed two to three times the normal range. 

Increased serum bile acids, suggesting cholestasis, were observed in rats treated with 1.57 mg selenium/kg/day as sodium selenate in drinking water for 13 weeks, but no effects were noted at 0.92 mg/kg/day (NTP 1994). In a 13-week drinking water study, hepatic effects were not observed in mice treated with sodium selenate at 7.17 mg selenium/kg/day, in mice treated with sodium selenite at doses up to 3.83 mg selenium/kg/day, or in rats treated with sodium selenite at doses up to 1.67 mg selenium/kg/day (NTP 1994). Increased serum aspartate aminotransferase and alanine aminotransferase activities were observed in mice treated by gavage with selenocystine at doses of 9.4 mg selenium/kg/day for 30 days (Sayato et al. 1993) or 4.7 mg selenium/kg/day for 90 days (Hasegawa et al. 1994). No effects on liver enzymes were observed in mice treated with selenocystine at 4.7 mg selenium/kg/day for 30 days (Sayato et al. 1993) or at 2.5 mg selenium/kg/day for 90 days (Hasegawa et al. 1994). Chronic dietary administration of selenium as seleniferous com or wheat at doses ranging from 0.25 to 0.50 mg/kg/day for 24 months produced cirrhosis of the liver in rats (Nelson et al. 1943). 

Many examples of aminotransferase activity have been described in helminths, although the enzymes have rarely been characterized (1,17). Most are specific for a-ketoglutarate as the amino acceptor but have broad specificity with respect to the amino donor. There is considerable variation in the potential amino acid donors from one species to another. Those aminotransferases that have been characterized show some similarities to rat liver enzymes. As in protozoa, alanine aminotransferase is ubiquitous and, together with asparate aminotransferase, is usually the most active member of this group. Isoenzymes of alanine aminotransferase have been found in both cytoplasm and mitochondria. The results of a survey of nematode alanine aminotransferases suggest that there is a greater overall capacity for the synthesis of alanine than for its catabolism, the opposite of the situation with the rat liver enzymes (17). 

The liver transaminases measured in the blood are aspartate aminotransferase (AST), which was formerly called serum glutamate-oxaloacetate transaminase (SCOT), and alanine aminotransferase (ALT), which was formerly called serum glutamate pyruvate transaminase (SGPT). Elevation of liver enzymes reflects damage of the liver plasma membrane. 

In postmenopausal women taking 40 mg black cohosh extract daily for 4 months, no changes in total hepatic blood flow, bilirubin, y-glutamyltransferase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, serum albumin, or prothrombin time and concentration were observed (Nasr and Nafeh 2009). No changes in liver enzyme levels were observed in other studies with women taking 40 mg black cohosh daily for 3 or 4 months, or in women given single doses up to 128 mg (Bai et al. 2007 Osmers et al. 2005 van Breemen et al. 2009). 

In men with positive prostate biopsies, oral administration of a standardized green tea extract containing 1.3 g green tea polyphenols (800 mg EGCG) daily for 12 to 214 days (mean of 34 days) was studied a decrease in liver enzyme levels, including aspartate aminotransferase, alkaline phosphatase, and amylase, was observed (McLarty et al. 2009). 

In rats orally administered 500 or 800 mg/kg of an ethanol extract of boldo or of the compound boldine daily for 90 days, increases in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and cholesterol were observed in the 800 mg/kg groups for both products after 30 or 60 days, but levels returned to normal after 90 days. A decrease in bilirubin was observed in the 800 mg/ kg groups for both products. No changes in liver enzymes or cholesterol levels were observed in the 500 mg/kg group (Almeida et al. 2000). 

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