On a typical hepatic panel, which pattern best distinguishes cholestasis from hepatocellular injury?

• A. Elevated ALT and AST with disproportionately high ALP elevation.
• B. Isolated ALT elevation with normal ALP.
• C. Very high bilirubin with low ALP.
• D. ALP and GGT markedly elevated with only modest ALT/AST elevations.

Answer: (D)

When the liver panel helps distinguish cholestasis from hepatocellular injury, focus on which enzymes rise and why. In cholestasis, bile flow is blocked, so the cells lining the bile ducts (and the biliary tree) respond by producing a lot of alkaline phosphatase; gamma-glutamyl transferase (GGT) also tends to rise with bile duct–related issues. The hepatocytes themselves aren’t damaged to the same extent, so the transaminases (ALT and AST) are only modestly elevated unless there’s concurrent hepatocyte injury. In hepatocellular injury, the primary signal comes from leakage of cytosolic enzymes ALT and AST from damaged hepatocytes, so these transaminases rise markedly while ALP and GGT are only moderately elevated.

Therefore a pattern with alkaline phosphatase and GGT markedly elevated and only modest elevations in ALT/AST is the classic signature of cholestasis, helping to distinguish it from hepatocellular injury.