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When and how to evaluate mildly elevated liver enzymes in apparently healthy patients

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ABSTRACTBecause 1% to 9% of people without symptoms have elevated liver enzymes, extensive evaluation of all abnormal test results would expose many patients to undue risks and expenses. On the other hand, failure to evaluate minor liver enzyme elevations could mean missing the early diagnosis of potentially treatable disorders. This review discusses likely causes of elevated aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase levels and provides algorithms for evaluating high liver enzyme values in apparently healthy patients in the primary care setting.

KEY POINTS

  • Nonalcoholic fatty liver disease is the most common cause of asymptomatic elevated aminotransferase levels.
  • Suspect alcoholic liver disease when the aminotransferases are elevated and the aspartate aminotransferase level is two to three times higher than the alanine aminotransferase level, especially when gamma-glutamyl transferase levels are elevated.
  • If medications or alcohol is a suspected cause of elevated aminotransferase levels, remeasure the levels after 6 to 8 weeks of abstinence.


 

References

In seemingly healthy patients, abnormal liver enzyme levels challenge even the most experienced clinicians in deciding what further evaluation to pursue, if any. Automated laboratory testing has made serum liver enzyme levels very easy to obtain, leading to an increase in testing and also in the number of incidental abnormal findings. An estimated 1% to 9% of people who have no symptoms have high liver enzyme levels when screened with standard biochemistry panels.1,2 A US survey2 showed elevated alanine aminotransferase (ALT) in 8.9% of surveyed people from 1999 to 2002, an increase from previous reports.

An extensive evaluation can be costly, anxiety-provoking, and risky, especially if it leads to unnecessary invasive procedures such as liver biopsy or endoscopic retrograde cholangiopancreatography (ERCP). Not all people with a single, isolated, mildly elevated liver enzyme value have underlying liver disease, nor do they require an extensive evaluation. Factors to consider when deciding whether to evaluate include:

  • The patient’s overall health, including chronic illness
  • The duration and pattern of enzyme elevation
  • Patient characteristics such as age, a personal or family history of liver, lung, or neurologic disease, risk factors for viral hepatitis, amount of alcohol consumption, use of prescribed or over-the-counter drugs or dietary supplements
  • The costs and risks associated with additional evaluation.

This article reviews the most likely causes of elevated aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase (GGT) levels. It also provides an algorithm for evaluating mildly abnormal liver enzyme values in apparently healthy people. Patients with signs of hepatic decompensation need a more concise and urgent evaluation.

PATTERNS OF LIVER ENZYME ELEVATION

“Liver function test” is commonly used to describe liver enzyme measurements, but the term should be reserved for tests of the functional hepatic reserve—traditionally, the albumin level and the prothrombin time.3

On the other hand, elevated serum liver enzymes (aminotransferases, alkaline phosphatase, and GGT) can reflect abnormalities in liver cells or in the bile duct. For example, predominant elevation of aminotransferases typically indicates hepatocellular injury, whereas elevated alkaline phosphatase and GGT indicates cholestatic injury. Elevated alkaline phosphatase and aminotransferases can indicate a mixed pattern of injury.

High AST, ALT suggest liver cell damage

Both aspartate aminotransferase (AST) and ALT are normally present in serum at low levels, usually less than 30 to 40 U/L. Although the actual values may differ from laboratory to laboratory, normal serum levels are usually less than 40 U/L for AST and less than 50 U/L for ALT. On the other hand, some experts have suggested lowering the upper limit of normal because of the increasing rate of obesity and associated nonalcoholic fatty liver disease, which may not be detected using the traditional, higher normal values. Acceptance is growing for using ALT levels less than 40 U/L in men and less than 31 U/L in women, and AST levels less than 37 U/L in men and less than 31 U/L in women, as normal thresholds.

Although ALT is present in several organs and in muscle, the highest levels are in the liver, which makes this enzyme a more specific indicator of liver injury. Both AST and ALT are released into the blood in greater amounts when hepatocytes are damaged.

Alkaline phosphatase suggests cholestasis

Alkaline phosphatase comes mostly from the liver and bone. In general, normal serum alkaline phosphatase levels in adults range between 20 and 120 U/L. When bone disease is excluded, an elevation suggests biliary obstruction, injury to the bile duct epithelium, or cholestasis. Additionally, there are rare cases of benign familial elevation of serum alkaline phosphatase, mainly of intestinal origin.

GGT is not specific

GGT is present in hepatocytes and biliary epithelial cells. The normal range is 0 U/L to 50 U/L in men, and 0 U/L to 35 U/L in women. GGT elevation is the most sensitive marker of hepatobiliary disease. However, its routine clinical use is not recommended, as it cannot by itself indicate a specific cause of liver disease, although measuring the GGT level can help determine a hepatic origin for an isolated elevation of alkaline phosphatase.

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