Aminotransferases

Liver chemistry tests are widely used to assess hepatic function. Common markers of hepatocellular damage are the aminotransferases, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). While AST is also found in other tissues, such as the heart, blood, and skeletal muscle, ALT is more specific for liver. The aminotransferases are released by hepatocytes with cell injury or death. The reference range is approximately 10 to 40 U/L for AST and 15 to 40 U/L for AST. The magnitude of the elevation of aminotransferases and the ratio of AST to ALT can help suggest the cause of liver disease. Mild elevation (<5 times the upper limit of normal) of the ALT or AST, with ALT > AST, is frequently found with chronic liver disease, including chronic viral hepatitis, fatty

Reduced Absorption

Malabsorption Malnutrition

Decreased Synthesis

Chronic liver disease Protein Catabolism

Infection

Hypothyroidism

Burns

Malignancy Chronic inflammation Increased Losses

Nephrotic syndrome Cirrhosis

Protein-losing enteropathies Hemorrhage

Dilutional

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Intravenous hydration

Table 15-5 Causes of Increased Alkaline Phosphatase Levels Table 15-6 Pattern of Liver Function Elevation

Bone Origin

Paget's disease

Osteomalacia

Rickets

Hyperparathyroidism

Metastatic disease

Liver Origin

Extrahepatic biliary obstruction

Pancreatic cancer

Biliary cancer

Common bile duct stone

Intrahepatic obstruction

Metastatic liver disease

Infiltrative diseases

Hepatitis

Primary biliary cirrhosis

Sclerosing cholangitis

Cirrhosis

Passive hepatic congestion

Other Causes

Drugs

Phenobarbital

Phenytoin

Chlorpropamide

Hyperthyroidism

Temporal arteritis

Test

Hepatocellular Disorders

Obstructive Disorders

Bilirubin

+

++

Aminotransferases

+++

+

Alkaline phosphatase

+

++

Y-Glutamyltransferase

+

++

Albumin

Decreased

Normal

liver, and medications. Probably the most common cause of persistently elevated unexplained aminotransferases is fatty infiltration of the liver. Less common causes of mildly elevated aminotransferases with ALT > AST include autoimmune hepatitis, hemochromatosis, alpha-1 antitrypsin disease, Wilson's disease, metastatic disease, and cholestatic liver disease. Mild aminotransferase elevations with AST > ALT are more suggestive of alcohol-related liver disease, but can also occur with cirrhosis and fatty liver. With alcoholic hepatitis, AST levels typically are approximately twice ALT levels, but the AST levels rarely are greater than 300 U/L. Marked elevations (greater than 15 times upper limit of normal) of AST and ALT suggest significant necrosis, such as seen in acute viral or drug-induced hepatitis, in ischemic hepatitis, or as can occur with acute biliary obstruction (Green and Flamm, 2002). However, the magnitude of elevation of the amino-transferases does not necessarily correlate with the severity of underlying liver disease or the prognosis. In fact, normal or minimally elevated aminotransferases may be seen in patients with end-stage liver disease. When AST is elevated without elevation of ALT, one should consider extrahepatic causes, particularly myocardial or skeletal muscle sources. When AST and ALT are elevated approximately the same, a hepatic origin is most likely. Table 15-6 compares the differences in liver function tests between hepatocellular and obstructive disorders.

Lactate dehydrogenase (LDH) is elevated in liver disease but is nonspecific; it is also found in skeletal muscle, cardiac muscle, blood, and some pulmonary disorders. Measurement of LDH rarely adds useful information to the evaluation of liver disease. GGT is a microsomal enzyme that is inducible by alcohol and certain drugs, including warfarin and some anticonvulsants. Although not specific for alcohol abuse, GGT is the most sensitive liver enzyme for alcohol abuse.

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