Abnormal Liver Chemistries: ACG Systematic Evaluation and Parenchymal Disease Workup
Hepatocellular vs. cholestatic pattern differentiation, isolated hyperbilirubinemia workup, and algorithmic evaluation of elevated transaminases.
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Clinical Recommendations
Liver chemistries including ALT, AST, alkaline phosphatase (ALP), and bilirubin are markers of liver INJURY, not liver FUNCTION, and should be referred to as "liver chemistries" or "liver tests" — NOT "liver function tests."
ALT is a more specific marker of hepatic injury than AST; elevated AST without elevated ALT is suggestive of cardiac or skeletal muscle disease.
An elevated ALP of hepatic origin should be confirmed by a concomitant elevation of gamma-glutamyl transferase (GGT) or by ALP isoenzyme fractionation.
Total serum bilirubin should be fractionated into direct (conjugated) and indirect (unconjugated) fractions when evaluating isolated hyperbilirubinemia or when aminotransferases and ALP are near normal.
The R ratio — calculated as (ALT ÷ ALT ULN) ÷ (ALP ÷ ALP ULN) — classifies the pattern of liver injury: >5 = hepatocellular; 2–5 = mixed; <2 = cholestatic.
Laboratory measurements of ALT, AST, and ALP are highly reproducible; inter-laboratory differences in values are not clinically significant. However, the defined upper limit of normal (ULN) varies substantially between institutions and should be interpreted with awareness of local reference ranges.
Primary Literature
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Protocol summaries are for clinical reference only. Always consult primary guidelines for full recommendations.