Why use it

Classifies DILI pattern to guide workup and management. Hepatocellular DILI has higher risk of acute liver failure (Hy Law). Part of RUCAM/CIOMS causality assessment. Helps determine which drugs are likely causative.

About

The R-factor (R-value) classifies the pattern of drug-induced liver injury (DILI) as hepatocellular, cholestatic, or mixed based on the ratio of ALT to ALP elevations (each expressed as multiples of their upper limit of normal). This classification is important for determining causality, prognosis, and management.

When to use

Suspected drug-induced liver injury
New liver enzyme elevation on medication
RUCAM causality assessment for DILI

Formula

R = (ALT / ALT ULN) / (ALP / ALP ULN) R > 5: Hepatocellular R 2-5: Mixed R < 2: Cholestatic

Pearls & pitfalls

R > 5 = hepatocellular pattern. R 2-5 = mixed. R < 2 = cholestatic pattern.
Hy's Law: hepatocellular DILI with bilirubin > 2× ULN (without obstruction) → ~10% risk of fatal ALF.
Use the FIRST set of abnormal labs (at onset of injury) for R-factor calculation.
Both ALT and ALP must be expressed as multiples of ULN (not raw values).
Common hepatocellular DILI drugs: acetaminophen, isoniazid, statins, NSAIDs.
Common cholestatic DILI drugs: amoxicillin-clavulanate, anabolic steroids, estrogens.

Next steps

R > 5 (hepatocellular): Higher risk of ALF — check INR, bilirubin (Hy's Law). R 2-5 (mixed): Intermediate pattern. R < 2 (cholestatic): Usually better prognosis; evaluate for biliary obstruction.

Evidence

Defined by the Council for International Organizations of Medical Sciences (CIOMS) in 1989. Integral to the RUCAM/CIOMS scale for DILI causality assessment. Widely used in hepatology and pharmacovigilance.

References

Danan G, Benichou C. Causality assessment of adverse reactions to drugs: a novel method based on the conclusions of international consensus meetings. J Clin Epidemiol. 1993;46(11):1323-1330. — link

R-Factor (Hepatotoxicity Pattern)

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