Limiting the Testing of AST
Objectives: Annually, millions of pairs of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) tests are ordered. These enzymes are highly correlated, and ALT is far more specific diagnostically than AST. To reduce AST testing, we suggest measuring AST only when ALT exceeds a predetermined limit.
Methods: We derived the proportions of elevated ASTs that would not be measured based on 15 months of paired inpatient and outpatient ALT and AST data.
Results: For inpatients, a 35 U/L ALT limit for initiating AST testing would reduce AST testing by 51%, missing only 3% and 7.5% of ASTs exceeding 50 U/L and 35 U/L, respectively. In outpatients, AST testing can be reduced by more than 65%, with fewer missed elevated ASTs (0.5% and 2% of the ASTs exceeding 50 U/L and 35 U/L, respectively).
Conclusions: Conservatively, $100 million could be saved annually in the US health care budget by selectively limiting AST testing in just the US outpatient environment.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes commonly ordered to ascertain hepatocyte integrity. ALT and AST are highly concentrated in the liver and catalyze the generation of pyruvic and oxalacetic acid, respectively. With hepatocellular injury, these enzymes are released into the plasma, leading to increases in their activity.
With acute liver damage, plasma AST activities are initially higher than ALT due to higher AST activities in the hepatocyte. Eventually, ALT activity exceeds AST, with its slower metabolism and longer half-life (47 hours vs 17 hours, respectively), meaning that most patients with liver disease would have an AST/ALT ratio (also called De Ritis ratio) of less than 1. Chronic alcohol intake, however, causes mitochondrial AST activity to be increased in plasma. Furthermore, patients who abuse alcohol can have decreased pyridoxal-5'-phosphate (vitamin B6), which decreases ALT activity. Overall, the AST/ALT ratio is increased in patients with alcoholic hepatitis, typically with a value greater than 1.5. As such, the De Ritis ratio putatively provides extra clinical information supporting the diagnosis of alcoholic hepatitis.
ALT is a more specific indicator of parenchymal liver disease than AST. ALT and AST are both present in high levels in the cytosol of the liver. AST is also present in the mitochondria of the liver and has significant activities in muscle, brain, pancreas, lung, kidney, erythrocytes, and leukocytes. ALT and AST are usually correlated, implying that a low ALT value would typically accompany a low AST value. Isolated AST elevations are generally due to nonhepatic sources (eg, arising from hemolyzed RBCs). In the past, AST has been used as an aid in diagnosing myocardial infarction and skeletal myopathy. For many years, troponin and creatine kinase, respectively, have been superior alternatives.
In many countries, these two tests are often ordered together. In a recent Centers for Disease Control and Prevention review of Medicare Part B–reimbursed laboratory testing, AST and ALT were the most frequently ordered hepatobiliary tests, with approximately 7,500 ALT and 7,500 AST tests ordered annually per 10,000 Medicare patients. In Canada and Europe, there is now pushback against AST testing. In 2007, the province of Ontario replaced AST with ALT on its requisition form. Four years later, annual AST testing in Ontario dropped from approximately 5 million to 2 million tests. In Sweden, AST is ordered less often than ALT. The ratio of ALT to AST tests ranges from six to 150. In Spanish emergency departments, a two-test screen consisting of ALT and alkaline phosphate (ALP) is used to work up hepatobiliary disease. This ALT/ALP combination was found to be adequate: ALT for identifying hepatocellular disease and ALP for liver tumors and biliary tract disease.
To reduce AST tests that are ordered in tandem with ALT, we propose measuring AST only when ALT exceeds a predetermined limit. In the steady state, hepatobiliary disease associated with an elevated ALT will usually be accompanied with an elevated AST. Conversely, in the absence of alcoholic liver disease, low ALT will usually be accompanied by low AST values. Through retrospective analysis of paired ALT and AST patient data, we determined the proportions of elevated AST that would not be measured based on the ALT limit.
Abstract and Introduction
Abstract
Objectives: Annually, millions of pairs of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) tests are ordered. These enzymes are highly correlated, and ALT is far more specific diagnostically than AST. To reduce AST testing, we suggest measuring AST only when ALT exceeds a predetermined limit.
Methods: We derived the proportions of elevated ASTs that would not be measured based on 15 months of paired inpatient and outpatient ALT and AST data.
Results: For inpatients, a 35 U/L ALT limit for initiating AST testing would reduce AST testing by 51%, missing only 3% and 7.5% of ASTs exceeding 50 U/L and 35 U/L, respectively. In outpatients, AST testing can be reduced by more than 65%, with fewer missed elevated ASTs (0.5% and 2% of the ASTs exceeding 50 U/L and 35 U/L, respectively).
Conclusions: Conservatively, $100 million could be saved annually in the US health care budget by selectively limiting AST testing in just the US outpatient environment.
Introduction
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes commonly ordered to ascertain hepatocyte integrity. ALT and AST are highly concentrated in the liver and catalyze the generation of pyruvic and oxalacetic acid, respectively. With hepatocellular injury, these enzymes are released into the plasma, leading to increases in their activity.
With acute liver damage, plasma AST activities are initially higher than ALT due to higher AST activities in the hepatocyte. Eventually, ALT activity exceeds AST, with its slower metabolism and longer half-life (47 hours vs 17 hours, respectively), meaning that most patients with liver disease would have an AST/ALT ratio (also called De Ritis ratio) of less than 1. Chronic alcohol intake, however, causes mitochondrial AST activity to be increased in plasma. Furthermore, patients who abuse alcohol can have decreased pyridoxal-5'-phosphate (vitamin B6), which decreases ALT activity. Overall, the AST/ALT ratio is increased in patients with alcoholic hepatitis, typically with a value greater than 1.5. As such, the De Ritis ratio putatively provides extra clinical information supporting the diagnosis of alcoholic hepatitis.
ALT is a more specific indicator of parenchymal liver disease than AST. ALT and AST are both present in high levels in the cytosol of the liver. AST is also present in the mitochondria of the liver and has significant activities in muscle, brain, pancreas, lung, kidney, erythrocytes, and leukocytes. ALT and AST are usually correlated, implying that a low ALT value would typically accompany a low AST value. Isolated AST elevations are generally due to nonhepatic sources (eg, arising from hemolyzed RBCs). In the past, AST has been used as an aid in diagnosing myocardial infarction and skeletal myopathy. For many years, troponin and creatine kinase, respectively, have been superior alternatives.
In many countries, these two tests are often ordered together. In a recent Centers for Disease Control and Prevention review of Medicare Part B–reimbursed laboratory testing, AST and ALT were the most frequently ordered hepatobiliary tests, with approximately 7,500 ALT and 7,500 AST tests ordered annually per 10,000 Medicare patients. In Canada and Europe, there is now pushback against AST testing. In 2007, the province of Ontario replaced AST with ALT on its requisition form. Four years later, annual AST testing in Ontario dropped from approximately 5 million to 2 million tests. In Sweden, AST is ordered less often than ALT. The ratio of ALT to AST tests ranges from six to 150. In Spanish emergency departments, a two-test screen consisting of ALT and alkaline phosphate (ALP) is used to work up hepatobiliary disease. This ALT/ALP combination was found to be adequate: ALT for identifying hepatocellular disease and ALP for liver tumors and biliary tract disease.
To reduce AST tests that are ordered in tandem with ALT, we propose measuring AST only when ALT exceeds a predetermined limit. In the steady state, hepatobiliary disease associated with an elevated ALT will usually be accompanied with an elevated AST. Conversely, in the absence of alcoholic liver disease, low ALT will usually be accompanied by low AST values. Through retrospective analysis of paired ALT and AST patient data, we determined the proportions of elevated AST that would not be measured based on the ALT limit.
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