Abnormal Test Values May Not Be Due to Liver Disease

The so-called liver chemistries may have extra-hepatic origin. For example patients with myopathies may have increased AST due to muscle injury, patients with celiac disease may have increased aminotransferases without liver disease, and patients with Paget's disease may have an increased bone alkaline phosphatase. Patients with Gilbert's Syndrome will have mild elevations in bilirubin due to an inherited gene mutation that causes reduced processing of bilirubin. Gilbert's is usually discovered by accident.

Some of the chemistries have physiologic variation. For example, alkaline phosphatase levels (from placenta) are typically elevated in pregnant women.

Mildly abnormal liver tests may occur in the setting of significant liver disease including hepatitis B, hepatitis C, and fatty liver disease. Early identification of these conditions can lead to treatment and prevention of advanced liver disease (cirrhosis, liver failure, and hepatocellular carcinoma). Hepatitis C is a curable viral infection while chronic hepatitis B can be managed successfully with oral therapy. Note: Thrombocytopenia may be the first clue of significant liver damage as up to 20% of patients with cirrhosis may have a normal ALT. Patients presenting with asymptomatic jaundice may have pancreatic cancer.

Liver Disease May Not Always Cause Abnormal Test Values

There may be fluctuations in disease activity. For example, aminotransferases in chronic hepatitis C usually fluctuate between normal and mildly elevated levels.

Some liver diseases may be subclinical. For example, patients with hemochromatosis may have normal liver tests until they present with cirrhosis.

The ranges of "normal" aminotransferase levels may be too high because normal laboratory ranges, currently used by local and reference laboratories, are typically determined in "healthy" reference populations, which may have included apparently well individuals with unrecognized liver disease such as undiagnosed viral hepatitis, alcohol abuse, herbal or medication consumption or fatty liver disease.

Liver tests by themselves are not meaningful! Abnormal liver tests must be interpreted in the context of clinical presentation.