Cholestasis Pattern in Elevated Transaminases

Definition and Calculation

The cholestasis pattern is defined by a value R ≤2, where R = (ALT/LSN)/(FA/LSN), indicating a predominance of alkaline phosphatase elevation over transaminases, according to the Journal of Hepatology 1
The value R is calculated by dividing the numerator (ALT expressed as multiples of the upper limit of normal (LSN)) by the denominator (alkaline phosphatase (FA) expressed as multiples of the LSN), as recommended by the Journal of Hepatology 1

A hepatocellular pattern is characterized by R ≥5, a cholestasis pattern by R ≤2, and a mixed pattern by R >2 and <5, as classified by the Journal of Hepatology 1

In the cholestasis pattern, elevations are characterized by alkaline phosphatase (FA) ≥2× LSN, particularly if there is a concomitant elevation of gamma-glutamyl transpeptidase (GGT) in the absence of bone disease, as indicated by the Journal of Hepatology 1
Transaminases (ALT/AST) are proportionally less elevated than FA, resulting in R ≤2, according to the Journal of Hepatology 1

It is crucial to confirm that the elevation of FA comes from the liver or biliary tract by measuring GGT, as recommended by Alimentary Pharmacology and Therapeutics 3
If GGT is normal, fractionation of FA isoenzymes should be performed to rule out a bone origin, as suggested by Alimentary Pharmacology and Therapeutics 3 and Praxis Medical Insights 4

In patients with chronic cholestatic liver disease, applying baseline values instead of LSN for monitoring FA is recommended, as advised by Alimentary Pharmacology and Therapeutics 3
FA >2× baseline should initiate increased monitoring, and FA >3× baseline or FA >2× baseline with bilirubin >2× LSN should trigger drug interruption, according to Alimentary Pharmacology and Therapeutics 3
Repeat tests in 7-10 days if cholestatic DILI is suspected, compared to 2-5 days for hepatocellular DILI, as recommended by Alimentary Pharmacology and Therapeutics 3

Elevations of FA with normal or minimally elevated AST/ALT suggest obstruction of the biliary tract (stones, stenosis, tumors), primary biliary cholangitis, drug-induced cholestasis, or infiltrative liver diseases, as indicated by Praxis Medical Insights 4