R-Factor Calculator (Liver Injury Pattern)
R-Factor Calculator (Liver Injury Pattern)
Classify liver injury as hepatocellular, cholestatic or mixed from ALT and ALP relative to their upper limits of normal.
R-Factor (Liver Injury Pattern)
ALT ÷ ALP, normalisedALT 320 (ULN 33), ALP 145 (ULN 129)
Formula
- ALT, ALP
- U/L
- upper limits
- your reporting laboratory's own — the ratio is sensitive to both
- R ≥ 5
- hepatocellular
- R ≤ 2
- cholestatic
- 2 < R < 5
- mixed
Worked example
ALT 320 (ULN 33), ALP 145 (ULN 129)
ALT ratio = 320 ÷ 33 = 9.70
ALP ratio = 145 ÷ 129 = 1.12
R = 9.70 ÷ 1.12 = 8.63 → hepatocellular
Patterns and their differentials
| R | Pattern | Consider |
|---|---|---|
| ≥ 5 | Hepatocellular | Viral hepatitis, drugs, autoimmune hepatitis, ischaemia, Wilson disease |
| 2 – 5 | Mixed | Drug-induced liver injury, sepsis, infiltration |
| ≤ 2 | Cholestatic | Biliary obstruction, drug cholestasis, PBC, PSC, sepsis |
Why the pattern comes first
The first useful question about abnormal liver tests is not how high they are but which pattern they form. Hepatocellular and cholestatic injury have almost entirely separate differentials and lead down different investigative paths, and the R-factor formalises that split into a single number.
Normalising each enzyme to its own upper limit is what makes the comparison valid. ALT and ALP have very different reference ranges and are measured on different scales, so a raw ratio would be meaningless. Dividing each by its own ULN puts them on a common footing — which also means the result depends on the reference limits used, and those differ between laboratories.
The R-factor is central to drug-induced liver injury, where it is part of the formal case definition and determines which causality assessment applies. It should be calculated on the first set of abnormal results, because the pattern of many drug injuries evolves — a hepatocellular presentation can become cholestatic over subsequent weeks, and classifying on a late sample misrepresents the injury.
In a hepatocellular pattern the next step is Hy’s law: a patient with ALT above three times the upper limit together with a bilirubin above twice the upper limit, without significant cholestasis, has a substantially raised risk of acute liver failure and needs urgent assessment.
Frequently asked questions
How is the R-factor calculated?
Divide ALT by its upper limit of normal, divide ALP by its upper limit of normal, then divide the first result by the second. R of 5 or more is hepatocellular, 2 or less is cholestatic, and in between is mixed.
Which upper limits of normal should I use?
Your reporting laboratory’s own. The ratio is directly sensitive to both, so using generic values from a textbook can shift a borderline case across a threshold.
When should the R-factor be calculated?
On the first available set of abnormal liver tests. Many drug injuries change pattern over subsequent weeks, so a late calculation misclassifies the injury.
What is Hy's law?
In a hepatocellular pattern, an ALT above three times the upper limit of normal with a bilirubin above twice the upper limit and no significant cholestasis predicts a substantially increased risk of acute liver failure.
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References
- Aithal GP et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89(6):806–15.
- Chalasani NP et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878–98.