Liver transaminase activities

Depressed liver transaminase activity after 60 days 10... 

Influence of CYP2D6 Genotypes on Liver Transaminase Activity... 

Table 10.9 Cytochrome P450 2D6 (C7P2 )(5)-rdated liver transaminase activity in Alzheimer s disease...

Oral human LDlq is equal to 221 mgkg Adverse acute reactions to bismuth include acute renal failure following ingestion of excessive concentrations. Bismuth can cause nausea, vomiting, and abdominal pain within hours of exposure. Muscle cramps and weakness, blurred vision, and hyperreflexia may be exhibited. Liver transaminase activities may be elevated. 

While considerable amounts of both GOT and GPT are found in cardiac muscle, skeletal muscle and kidney, differential diagnosis is aided by the fact that the liver shows a much higher total GPT activity. An important clinical application of measurements of transaminase activity is the detection and diagnosis of viral... 

Fenvalerate inhibits intercellular communication between fibroblast cells and enhances the development of hepatocyte foci in rat liver at nonhepatotoxic dose levels. Chemicals that possess these properties are likely to be tumor promoters (Flodstrom et al. 1988). Fenvalerate alone induced no hepatotoxic effects in rat liver, as judged by transaminase activities and histology. However, some rats that were partially hepatectomized and insulted with nitrosodiethylamine — a carcinogen and tumor initiator — had significantly elevated numbers of liver foci after administrations of fenvalerate. This response suggests that fenvalerate is a potential tumor promoter (Flodstrom et al. 1988). 

After 48 h, marked increase in blood glucose, depressed plasma insulin level, marked depletion of liver glycogen, significant increase in plasma creatinine phosphokinase and glutamic oxaloacetic transaminase activity (Giri etal. 1979)... 

Hepatic Effects. No studies were located regarding hepatic effects in humans after exposure to 3,3 -dichlorobenzidine. Information from animal studies on the liver effects of exposure to 3,3 -dichloro-benzidine suggests that exposme to sufficiently high levels of the compoimd could cause liver injury as indicated by modest elevation in serum transaminase activity, fatty liver (Stula et al. 1978), decrease in hepatic vitamin E, and lipid peroxidation (Iba 1987a Iba and Lang 1988 Iba and Thomas 1988). Some of these effects may contribute to the liver tumors induced. However, it is not known whether these liver injuries will occur in humans exposed to 3,3 -dichlorobenzidine at levels at which it occurs at hazardous... 

In a long-term inhalation study in rats, exposure to 1,4-dichlorobenzene at air concentrations of 490-499 ppm 5 hours per day, 5 days per week for 76 weeks resulted in an increase in absolute liver weight throughout the study in males and at weeks 27 and 112 in females (Riley et al. 1980). This effect was not accompanied by histological alterations or by increased serum transaminase activities. No hepatic effects were noted at 75 ppm. None of the adverse hepatic effects reported at lower concentrations of 1,4-dichlorobenzene for shorter durations (Hollingsworth et al. 1956), as described above, were identified in the 76-week study. Based on the NOAEL of 75 ppm for lack of hepatic effects, a chronic-duration MRL of 0.1 ppm was calculated as described in the footnote to Table 2-1 and in Appendix A (Hollingsworth et al. 1956). 

Transaminases are also found in other tissues, from which they leak from the cells into the blood when injury occurs. Measurement of serum enzyme activity (serum enzyme diagnosis see also p. 98) is an important method of recognizing and monitoring the course of such injuries. Transaminase activity in the blood is for instance important for diagnosing liver disease (e.g., hepatitis) and myocardial disease (cardiac infarction). 

In a 40-week study in which rats were administered 2-hexanone at 400 mg/kg/day, the levels of liver enzymes (alanine aminotransaminase and aspartate transaminase activities) measured at 4- week intervals were normal (Eben et al. 1979). 

Curcumin (9) is an arylheptanoid isolated from turmeric, the rhizome of Curcuma longa L. Turmeric has been used as a remedy for inflammatory in Asia for centuries. There are a number of reports supporting an anti-inflammatory effect of curcumin. Its hepatoprotective activity against inflammatory liver injury was also demonstrated in a recent study [105], where pretreatment with curcumin (50 mg/kg, p.o.) significantly inhibited the elevation of serum transaminase activities after intoxication with D-GalN and LPS in mice. The hepatoprotective effect is presumably... 

Comparable reports have prompted a questionnaire investigation of 770 patients with type 2 diabetes at the start of acarbose therapy (62). Patients with one or more susceptibility factors for liver damage underwent ultrasonography and autoantibody assays. There was silent liver disease in 13% and 20 patients had a fatty liver without hepatic disease. In 15% of these patients there were slight reversible changes in transaminase activity after acarbose. 

In a 56-week study there was an association between the dose of acarbose in the range 50-300 mg tds and the development of abnormal liver function in 359 patients with type 1 (21%) and type 2 diabetes (38). The patients took the maximum tolerated dose, and 30% took doses of 100 mg or less. Of the patents who were randomized to acarbose (n = 240), 8% developed abnormal liver function tests (alanine transaminase activity more than three times the upper limit of normal) compared with 1% of those who took placebo (n — 119). The dose of acarbose was 200-300 mg tds in those who developed abnormal liver function. Liver function recovered promptly on withdrawal. 

A 73 year old Japanese woman, weight 33.5 kg, took nateglinide 270 mg/day and pioglitazone 15 mg/day for 6 months (105). Her HbAic concentration was 8.6% and fasting glucose 11.4 mmol/1. Metformin 250 mg bd was added and 3 weeks later she developed jaundice and fatigue. A few months before her liver function tests had been normal. Aspartate transaminase activity was 689 IU/1, alanine transaminase 772 IU/1, alkaline phosphatase 639 IU/1, and bilirubin 6.5 mg/dl. All oral therapy was withdrawn and insulin started. Her liver function improved over the next few weeks. 

The incidence of drug-induced liver injury with rosiglitazone has been calculated at 0.02% for alanine transaminase activity 10 times the upper end of the reference range and 0.001% for jaundice (120). The above case report is unusual because, although liver damage is rare, hepatic necrosis occurs more commonly than cholestatic hepatitis. 

Two patients developed significantly abnormal liver function tests after receiving pegvisomant for 12 weeks (2,3). Transaminase activities rose to more than 10-fold the upper limits of the reference ranges and returned to normal after withdrawal. One of the two was treated for autoimmune hepatitis (5). Monitoring of liver enzymes every 4-6 weeks is recommended for 6 months or if symptoms of hepatitis develop. 

Based on the low frequency of raised alanine transaminase activity and the lack of clinical evidence of hepato-toxicity, some clinicians have called for a change in the current practice of monitoring liver function tests. However, a 71-year-old woman taking atorvastatin had raised transaminase activity on two occasions and developed pruritus on rechallenge. Thus, clinicians should be aware of asymptomatic rises in liver function tests in patients taking atorvastatin who do not have known susceptibility factors for liver damage (15). 

Possible mechanisms of fenofibrate-induced liver injury include activation of peroxisome proliferation-activator receptors, a hypersensitivity reaction, and immune -mediated injury from cross-reactivity of the drug with autoantigens. The authors referred to six reported cases of hepatic fibrosis attributed to fenofibrate. Raised transaminase activities occur commonly with fenofibrate but are generally transient, reverse on withdrawal, and do not result in long-term injury. Fenofibrate should be withdrawn if higher than normal enzyme activities persist, and a liver biopsy should be considered if liver enzymes do not normalize after withdrawal. 

HMG CoA reductase inhibitors can be associated with small rises in alanine transaminase activity, but have not been definitely associated with severe morbidity involving altered hepatic function. The results of randomized trials do not suggest that statins in standard doses are hepato-toxic. In none of the large randomized studies in which standard doses were assessed (atorvastatin 10 mg/day, fluvastatin 40-80 mg/day, pravastatin 40 mg/day, simvastatin 20-40 mg/day) was there any clear excess risk of hepatitis or any other serious liver-related adverse events. Long-term large randomized trials have confirmed an excess of persistent rises in transaminases with atorvastatin 80 mg/day compared with lower doses or placebo, and similarly some excess with simvastatin 80 mg/day, but hepatitis and liver failure were not reported (4). 

In a comparison of atorvastatin with pravastatin, of 224 patients taking atorvastatin, two had clinically significant increases in alanine transaminase activity (32). They recovered during the next 4 months, one after withdrawal of atorvastatin and the other after a dosage reduction. Withdrawals due to adverse effects were similar in the two groups. One patient developed hepatitis while taking atorvastatin, but was able to tolerate simvastatin (33). The authors concluded that this adverse effect was not a class effect. Eosinophils in a liver-biopsy specimen pointed to an immunological mechanism. 

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