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Am Fam Physician. 2003;67(5):1092-1094

The widespread frequency of serum blood chemistry analyses in medicine requires an appropriate guideline for evaluating abnormal test results. Guidelines have been developed by the Clinical Practice Committee of the American Gastroenterological Association to interpret results and follow patients with abnormal liver chemistry test results.

Because normal values for serum biochemical tests are defined by the mean of the distribution plus or minus two standard deviations among a healthy population, 2.5 percent of healthy persons will have abnormal test elevations. In addition, because a normal value does not exclude the possibility of hepatic disease, test results must be interpreted in the context of the individual patient, and a detailed history, physical examination, and medication review are required. Important factors in this evaluation include risk factors for liver disease, medications associated with liver chemistry abnormalities, comorbid conditions, alcohol consumption, and other evidence of liver disease. This information base may appropriately direct the examination toward establishing specific diagnoses. When no clues exist or a diagnosis cannot be confirmed, an algorithm for evaluation of liver test abnormalities can be useful.

Elevated serum aminotransferase levels indicate the need to test for common hepatic diseases with noninvasive testing. If these results are negative, further testing should be based on the clinical situation. Clinical follow-up and serial serum liver chemistry testing is important. If aminotransferase elevations are persistent or marked, or if there is evidence of liver disease, a more complete diagnostic effort is required, which may include radiologic testing and liver biopsy.

Hyperbilirubinemia can be caused by hepatocellular, cholestatic, or metabolic diseases and requires further evaluation. Initial evaluation should identify whether hyperbilirubinemia is conjugated (direct) or unconjugated (indirect). Mild indirect hyperbilirubinemia in an asymptomatic patient may indicate

Gilbert's syndrome, hemolysis, or a medication adverse effect. Conjugated hyperbilirubinemia in the presence of an elevated alkaline phosphatase level warrants evaluation for biliary obstruction with ultrasonography.

An elevated serum alkaline phosphatase level in the presence of normal aminotransferase levels warrants testing of γ-glutamyl-transferase or 5-nucleotidase testing. If these results are negative, some other etiology should be sought for the elevated serum alkaline phosphatase level outside of the hepatobiliary tract. If these results are positive, further testing is necessary to look for biliary obstruction, medication adverse effects, or primary biliary cirrhosis.

The authors conclude that mild liver abnormalities found in patients who appear to be healthy can be followed up closely if initial testing for common liver disease is negative. Further evaluation is essential in patients who have significant symptoms, chronic or serious liver disease, and marked laboratory abnormalities.

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