The liver, which is located in the right upper abdominal cavity, is an actor that truly plays many roles in the stage of life. Just a partial list of the liver’s many functions includes the formation of plasma proteins, the breakdown of medications and harmful substances, conversion of glucose into the starch glycogen for future energy use, production of bile for use in fat digestion and removal of waste products, and the production of cholesterol.

Commonly measured liver enzymes include ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma glutamyl transpeptidase), and alkaline phosphatase. ALT and AST are referred to as the transaminases.

While ALT is found mainly in the liver, AST can also be found in heart and skeletal muscle, the kidney, red blood cells, and other locations.

Causes and Diagnosis

The most common cause of transaminase elevation is nonalcoholic fatty liver disease (NAFLD), which affects about 30% of adults in the United States. Risk factors for NAFLD include obesity, diabetes, elevated lipids, and the metabolic syndrome.

NAFLD spans a range from steatosis (fatty liver), which is more commonly seen and which is more benign, to nonalcoholic steatohepatitis (also called NASH), which is more serious and is characterized by liver inflammation and fibrosis. Liver imaging cannot reliably identify NASH, which is diagnosed with a liver biopsy.

Many types of medications can cause elevated liver enzymes, such as statins, NSAIDs, acetaminophen, and seizure medications, as can herbal supplements, chemicals, pesticides, and metals.

Hepatitis viruses A, B, C, D, and E all affect the liver, and types B, C, and D can cause chronic infection. Other viruses can also elevate the liver enzymes, such as Epstein-Barr virus, which causes mononucleosis.

A number of other conditions can also affect the liver, including hemochromatosis, an inherited disorder that results in iron overload in the liver and other organs.

Transaminase elevations can also be due to conditions external to the liver, such as inflammatory bowel disease, celiac disease (caused by an allergy to gluten in the diet), muscle disease, strenuous exercise, and thyroid disease.

Elevated GGT levels have been found to be associated with increased mortality, not only from liver disease, but also from cardiac disease, diabetes, and cancer. For that reason, even an isolated GGT elevation can be concerning in someone who is not felt to have liver disease.

An important cause of GGT elevation is alcohol ingestion. Alcoholic liver disease is a common cause of elevated liver enzymes. In addition to GGT, alcohol can also elevate the transaminases, often AST to a larger extent than ALT. In the face of abnormal liver enzymes, an AST/ ALT ratio over two (AST more than twice as high as ALT) is suggestive of alcoholic liver disease, although lower ratios do not rule it out.

Common causes of alkaline phosphatase elevation include liver and gallbladder disease, pregnancy, bone disease, normal bone growth as occurs during childhood and adolescence, and healing bone fractures. Alkaline phosphatase elevation is expected during pregnancy and is not a reason for concern nor a reason to rate a case. Elevations of both alkaline phosphatase and GGT suggest a liver source.

The evaluation of abnormal liver enzymes is individualized based upon the doctor’s suspicion of serious disease, and might range from observation with periodic retesting to more intensive investigation that might include further blood testing, liver imaging (such as sonogram, CT scan, or MRI), and perhaps even liver biopsy.

Underwriting Liver Enzyme Abnormalities: Case Studies

Applicant 1 has on insurance testing an ALT of 85, GGT of 125 and the rest of the liver tests are normal. Hepatitis B and C serologies and a CDT (screening for excess alcohol intake) are all negative. The medical history is unremarkable and no prior lab test testing is available. This would be Standard Plus using credits from the negative testing.

Applicant 2 has on insurance testing an alkaline phosphatase of 250, GGT of 200, and an ALT of 300. The last physical examination occurred one year prior to application, at which time the liver enzymes were normal. This is a decline.

Applicant 3 has on insurance testing an ALT of 125, GGT of 150 and the rest of the liver tests are normal. Hepatitis B and C serologies are negative and a CDT cannot be run. This case would be Table 2.

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