Transaminases liver function test

Hepatic Effects. Jaundice and abnormal liver function tests including increases in serum transaminase levels have been reported in individuals occupationally exposed to trichloroethylene by both dermal and inhalation exposure (Bauer and Rabens 1974 Phoon et al. 1984). 

FIGURE 21-1. Interpretation of liver function tests. (ALT, alanine transaminase AST, aspartate transaminase CT, computed tomography DDX, differential diagnosis GGT, y-glutamyl transpeptidase.)... 

Determination of the level of cytosolic enzymes such as aspartate transaminase, alanine transaminase, and lactate dehydrogenase is part of standard biochemical liver function tests to measure hepatocellular necrosis [2, 101]. Cytosolic enzymes are not subject to genetic variations inherent in microsomal enzyme production. Liver cytosolic enzymes metabolize several molecules, of which galactose and amino acids are typical examples, used for hepatic function tests. 

Hepatotoxicity Fever has occasionally occurred within the first 3 weeks of therapy, sometimes associated with eosinophilia or abnormalities in 1 liver function test or more. Jaundice with or without fever may occur, usually within the first 2 to 3 months of therapy. Incidence of elevated serum transaminase levels and impaired hepatic function ranges from 1% to 27%. 

Perform liver function tests on all patients during therapy with nicotinic acid. Monitor serum transaminase levels, including ALT and AST, before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (at approximately 6-month intervals). Discontinue the drug if the transaminase levels show evidence of progression, particularly if they rise to 3 times the upper limit of normal and are persistent or if they are associated with symptoms of nausea, fever, or malaise. Consider liver biopsy if elevations persist beyond discontinuation. 

Hepatotoxicity A few cases of reversible clinical hepatotoxicity have occurred in some patients, asymptomatic rises in serum alkaline phosphatase or serum transaminase levels have been observed. If anorexia, weight loss or pruritus develop in patients on allopurinol, evaluation of liver function should be part of their diagnostic workup. Perform periodic liver function tests during early stages of therapy. 

Hepatic complications Perform periodic liver function tests, such as bilirubins, alkaline phosphatase, or transaminases during therapy discontinue at the first sign of hepatic dysfunction or jaundice. 

Nausea vomiting diarrhea (clindamycin 3.4% to 30%) pseudomembranous colitis (clindamycin 0.01% to 10% 3 to 4 times more frequent with oral administration) neutropenia (sometimes transient) leukopenia agranulocytosis thrombocytopenic purpura skin rashes, urticaria, erythema multiforme anaphylaxis jaundice liver function test abnormalities (serum transaminase elevations). 

Transient abnormalities in liver function tests (eg, elevation in serum bilirubin, alkaline phosphatase, serum transaminases), and reduced biliary excretion of contrast media used for visualization of the gallbladder have also been observed. Drug/Food interactions Food interferes with the absorption of rifampin, possibly resulting in decreased peak plasma concentrations. Take on an empty stomach with a full glass of water. 

It may be prudent to consider liver function testing of patients being treated with nefazodone. Periodic serum transaminase testing has not been proven to prevent serious injury, but it is generally believed that early detection of drug-induced hepatic injury, along with immediate discontinuation of the medication enhances the likelihood for recovery. 

Transient mild elevations of liver function tests, particularly serum glutamic-pyruvic transaminase (SGPT) (typically presents and resolves within first 6 weeks of treatment)... 

CBZ can cause a mild, transient increase in serum transaminases and alkaline phosphatase levels. They usually do not exceed 1.5 times normal levels and subside with ongoing treatment. If liver function tests (LFTs) increase two to three times normal levels, hepatotoxicity may result. With prolonged CBZ therapy, a syndrome resembling a mild viral hepatitis may occur but usually improves after drug discontinuation. 

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. 

A 38-year-old woman was given insulin when glibenclamide and acarbose failed. Troglitazone 400 mg/day was added and increased to 800 mg/day 1 month later. After 2 months her liver function tests were normal, but she developed jaundice after 4 months. Total and direct bilirubin were 127 and 101 pmol/l and alanine transaminase was 34 pkat/l. After withdrawal of troglitazone her symptoms disappeared and her liver function tests normalized within several months. Metformin 1000 mg bd reduced her insulin requirement. Rosiglitazone 4 mg bd was added and her liver function tests remained normal for 10 months. 

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). 

A 65-year-old man with type Ha dyslipidemia who took flavored colestipol granules 2 scoops/day for 3 months developed asymptomatic hepatotoxicity (11). Several of his liver enzymes were raised to 10 times the upper limit of the reference range. One week after withdrawal of colestipol, his serum transaminases fell dramatically and 3 weeks later all his liver function tests were normal. 

Objective measures of disease. The clinical team will monitor the patient s response to treatment by CT scan or other objective measure of tumour size in any original sites of disease (i.e. primary tumour in the breast or sites of metastases). This is typically done every 6-8 weeks during treatment. Monitoring of liver function tests is appropriate as an improvement in Mrs CR s transaminase and GGT levels may indicate disease response conversely a worsening of these parameters may indicate unresponsiveness to treatment. 

There is no indication for routine liver function tests in patients taking tricyclic antidepressants raised transaminases and alkaline phosphatase within the limits of the reference ranges are not a cause for serious concern, unless they are accompanied by clinical signs or symptoms indicative of liver dysfunction. 

A 44-year-old woman developed weakness with abnormal liver function tests (aspartate transaminase 661 IU/1) about 6 months after starting to take venlafaxine 150 mg/day. Biopsy showed confluent necrosis in zone 3, with unaffected portal tracts. No other cause for the hepatitis could be found. The clinical and biochemical features resolved within 12 weeks of withdrawal of venlafaxine. 

Patients must be monitored carefnlly for signs of myopathy and hepatotoxicity. Elevations of transaminases as a possible pharmacodynamic effect of lipid-lowering therapy should be considered. Liver function tests (LFTs) shonld be monitored to identify possible hepatotoxicity. Statins shonld be withheld or changed if elevations in transaminases are persistently more than three times ULN or are accompanied by other signs of liver disease that might be iatrogenic. In addition, the patient mnst be adequately monitored in order to identify ... 

FIGURE 21-1. Interpretation of liver function tests. (ALT, alanine transaminase ... 

A 63-year-old man, who had taken amiloride and alfuzosin for 9 months for hypertension and benign prostatic hyperplasia, became jaundiced. His aspartate transaminase was 3013IU/1, alanine transaminase 2711 IU/1, alkaline phosphatase 500 IU/1, and total bilirubin 415 pmol/l. Viral causes, autoimmune hepatitis, and biliary obstruction were excluded. After withdrawal of alfuzosin, his liver function tests gradually returned to normal within 6 months. 

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