Elevated alanine aminotransferase

The nurse immediately reportsany elevated alanine aminotransferase (ALT) level to the primary health care provider. The primary health care provider may want to continue monitoring the ALT level or discontinue use of the drug because of the danger of hepatotoxidty. However, abrupt discontinuation may cause a decline in cognitive functioning. 

May present with high fever with significant leukocytosis with left shift, anemia, elevated alanine aminotransferase, and dull abdominal pain on palpation... 

The most common adverse effects of lamivudine seen at doses used to treat HBV are mild they include headache, malaise, fatigue, fever, insomnia, diarrhea, and upper respiratory infections. Elevated alanine aminotransferase (ALT), serum lipase, and creatine kinase may also occur. The safety and efficacy of lamivudine in patients with decompensated liver disease have not been established. Dosage adjustment is required in individuals with renal impairment. Coadministration of trimethoprim-sulfamethoxazole decreases the renal clearance of lamivudine. 

A study, undertaken to confirm the involvement of the cytochrome P450 isoenzyme CYT2D6 in the metabolism of trazodone, found that when 11 depressed patients were given trazodone 150 to 300 mg at bedtime for 18 weeks, and then with thioridazine 20 mg twice daily for one week, the plasma levels of the trazodone and its active metabolite, /w-chlorophenyl-piperazine, rose by 36% and 54%, respectively. No adverse reactions were described. In contrast, a case of fatal hepatic necrosis with cholestasis has been attributed to the concurrent use of trazodone and phenothiazines. A 72-year-old woman taking trifluoperazine, trazodone and lithium carbonate developed an elevated alanine aminotransferase level. Trifluoperazine was replaced with thioridazine, but 9 weeks later she became jaundiced and developed hepatic encephalopathy, and died 6 weeks after the onset of jaundice. The authors consider that the combination of the phenothiazines and trazodone were the cause of her hepatic necrosis both phenothiazines and trazodone have been reported to individually cause hepatic adverse effects. ... 

The hallmark of acnte HBV infection is elevated alanine aminotransferase (ALT) levels. As a matter of fact, ALT levels are routinely screened during our annual physical exams where an elevated ALT level is a sign of a concern with regard to the... 

In clinical trials, patients were identified based on the molecular analysis using the same diagnostic kit from Abbott employed to detect ALK fusions. Crizotinib was administrated orally at the standard dose of 250 mg twice daily in a 28-day cycles. Based on a cohort of 50 advanced NSCLC patients with ROS 1 rearrangement, the ORR was 72%. The safety profile of crizotinib in these new patient populations was similar to that observed in patients harboring ALK-fusion mutations. For example, the most common treatment-related adverse effects (grade 3) were hypophosphatemia, neutropenia, and an elevated alanine aminotransferase level. There were no treatment-related grade 4 or 5 adverse events in the ROSl patients." ... 

Over a 9-year review period, 109 children had an adverse reaction to TMP-SMX. Of which, 40 required hospitalisation, with common adverse events in the hospitalised group including, rash, fever, mental status change, mucous membrane involvement, vomiting, diarrhoea, cytopenia and elevated alanine aminotransferase [144 ]. 

When administering tacrine, the nurse must monitor the patient for liver damage. This is best accomplished by monitoring alanine aminotransferase (AIT) levels. ALT is an enzyme found predominately in the liver. Disease or injury to the liver causes a release of tiiis enzyme into the bloodstream, resulting in elevated ALT levels, hi patients taking tacrine, ALT levels should be obtained weekly from at least week 4 to week 16 after die initiation of tiierapy. After week 16, transaminase levels are monitored every 3 months. 

HCV infection is rarefy diagnosed in the acute phase, as most acutely infected individuals are asymptomatic. Between 50% and 90% of patients develop chronic infection, however, and this warrants early therapy. After occupational exposure with a known date, treatment should not be started before the acute episode characterized by alanine aminotransferase elevation, but it should always be started within 24 weeks after the onset of symptoms. The optimal treatment schedule for acute hepatitis C is controversial. Pegylated IFN-a monotherapy at the standard dose for 24 weeks yielded SVR rates close to 100% in symptomatic patients referred to tertiary care centers (De Rosa et al. 2006 Jaeckel et al. 2001 Santantonio et al. 2005 Wiegand et al. 2006). Shorter therapy may be envisaged (Calleri et al. 2007). Combination with ribavirin is recommended if a first course of pegylated IFN-a monotherapy fails to eradicate the infection. Viral elimination appears to be independent of the HCV genotype and the HCV RNA level (Calleri et al. 2007 De Rosa et al. 2006 Jaeckel et al. 2001). 

Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, y-glutamyl transferase, and bilirubin may be elevated in patients with hepatobiliary disease. 

Hepatocellular damage manifests as elevated serum aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]. The degree of transaminase elevation does not correlate with the remaining functional metabolic capacity of the liver. An AST level two-fold higher than ALT is indicative of alcoholic liver damage. 

Toxicities are GI (stomatitis, diarrhea, nausea, vomiting), hematologic (thrombocytopenia, leukopenia), pulmonary (fibrosis, pneumonitis), and hepatic (elevated enzymes, rare cirrhosis). Concomitant folic acid may reduce some adverse effects without loss of efficacy. Liver injury tests (aspartate aminotransferase or alanine aminotransferase) should be monitored periodically, but a liver biopsy is recommended during therapy only in patients with persistently elevated hepatic enzymes. MTX is teratogenic, and patients should use contraception and discontinue the drug if conception is planned. 

Constipation occurs in fewer than 10% of patients taking statins. Other adverse effects include elevated serum aminotransferase levels (primarily alanine aminotransferase), elevated creatine kinase levels, myopathy, and rarely rhabdomyolysis. 

Use of zileuton is limited due to the potential for elevated hepatic enzymes (especially in the first 3 months of therapy), and inhibition of the metabolism of some drugs metabolized by CYP3A4 (e.g., theophylline, warfarin). Serum alanine aminotransferase should be monitored before treatment and then periodically thereafter. 

Primates offer all of the possible dosing routes available in humans, but body size often limits dosing volumes. If volumes for subcutaneous or intramuscular injections exceed those suggested above, enzyme elevations [particularly alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] are frequently observed (unpublished results). Continuous infusion techniques in alert animals are available in some laboratories either through use of programmable backpack pumps or jacket-and-tether systems (Perkin and Stejskal, 1994). 

Hepatic Effects. Enlarged liver and elevated serum levels of hepatic enzymes indicative of liver injury (lactate dehydrogenase, 2 times above normal aspartate aminotransferase, 21 times above normal alanine aminotransferase, 100 times above normal) were observed in an individual following chronic daily exposure to vapors and spills of phenol (Merliss 1972). The symptoms lessened when the... 

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... 

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... 

Serum chemistry markers play an important role in hepatotoxicity evaluation in human and animal safety studies. The classic markers of hepatotoxicity are alanine aminotransferase (ALT), aspartate aminotrasnferase (AST) and alkaline phosphatase (ALP) [124—127]. Drug-induced hepatotoxicity can be difficult to assess in some circumstances. Hepatotoxic responses can be intrinsic (predictable, dose-related) or idiosyncratic (unpredictable, non-dose-related). ALT, AST and ALP are generally not useful for predicting idiosyncratic responses. The administration of some drugs, such as isoniazid, can lead to a high incidence of ALT elevation, but are tolerated by most patients without severe hepatotoxicity. Adverse drug reactions can be masked... 

Hepatic Effects. Liver injury, characterized by an elevated serum enzyme (alanine aminotransferase level), was described in case reports of three humans after dermal application of carbon tetrachloride (Perez et al. 1987). In the absence of quantitative estimates of the amount of carbon tetrachloride applied or absorbed, NOAEL and LOAEL values cannot be determined. 

Hepatotoxicity. Duloxetine is rarely associated with increases in serum transaminase levels, typically in the first 2 months of treatment. In controlled trials in major depressive disorder, elevations of alanine aminotransferase (ALT) to greater than three times the upper limit of normal occurred in 0.9% (8 of 930) of the duloxetine-treated patients and in 0.3% (2 of 652) of the placebo-treated patients. Current product labeling contains a caution regarding the use of duloxetine in patients with significant alcohol use or chronic liver disease. Postmarketing reports have indicated that increases in transaminases have occurred in some patients with chronic liver disease (Cymbalta 2005). 

Some cases of hepatotoxicity have been reported to be associated with exposure to coumarin. One possible case was reported by Beinssen (1994) and six by Loprinzi et al. (1997). Marshall et al. (1994) reported one case in which elevated serum aminotransferase levels were measured in a patient given 5 g coumarin per day. In two lymphoedema patients given 90 mg coumarin per day for five months, Koch et al. (1997) reported elevated serum alanine aminotransferase activity. Faurschou (1982) reported a case of toxic hepatitis in a patient given coumarin daily for eight weeks, which was characterized by hepatomegaly and elevated serum enzyme levels. All signs of liver toxicity returned to normal on cessation of treatment. 

A single oral dose (> 400 mg/kg bw) of 1,2-dichloroethane to B6C3Fj mice induced an elevation of alanine aminotransferase activity and an increase in relative liver weight, and some mortality occurred. The lowest intraperitoneal dose inducing an elevation of these enzy mes was 500 mg/kg bw intraperitoneal doses of up to 600 mg/kg bw did not kill any of the animals ( = 5). Inhalation exposure to 500 ppm [2000 mg/m ] for 4 h was hepatotoxic to some of the mice, while at 150 ppm [600 mg/m- ] no toxicity was observ ed. Relative kidney weight was elevated after 300 mg/kg bw orally, 400 mg/kg bw intraperitoneally and after a 4-h exposure to 500 ppm 1,2-dichloroethane (Storer et al., 1984). 

---