Hepatology
R Factor (Liver Injury Pattern)
Hepatocellular vs cholestatic injury.
Education and reference only. Not a substitute for clinical judgement, local policy or product labelling. Always verify before clinical use. Values are calculated in your browser and never stored.
Background
The R factor classifies the pattern of liver injury when liver enzymes are abnormal, particularly in suspected drug-induced liver injury (DILI). It compares the relative rise in alanine aminotransferase (ALT), a marker of hepatocyte damage, against alkaline phosphatase (ALP), a marker of cholestasis. R is calculated as (ALT ÷ ALT upper limit of normal) divided by (ALP ÷ ALP upper limit of normal), using the local laboratory's reference limits. The result separates injury into hepatocellular, mixed and cholestatic patterns.
Interpreting the result
An R value of 5 or more indicates a hepatocellular pattern, where the dominant disturbance is hepatocyte injury. A value of 2 or less indicates a cholestatic pattern, dominated by impaired bile flow. Values between 2 and 5 represent a mixed pattern. The pattern narrows the differential diagnosis and directs further investigation, but it describes the type of injury rather than its severity.
Worked example
A patient has ALT 300 U/L (ULN 40) and ALP 150 U/L (ULN 120). R = (300/40) ÷ (150/120) = 7.5 ÷ 1.25 = 6. An R of 6 indicates a hepatocellular pattern of injury.
Critical actions
R = (ALT/ALT-ULN) ÷ (ALP/ALP-ULN). Use your lab's upper limits of normal. It classifies pattern, not severity.
Pearls / pitfalls
- Use the value taken at the onset of injury — R can shift over time as enzymes evolve, so serial values may reclassify the pattern.
- Always use your own laboratory's upper limits of normal, as reference ranges differ between assays.
- R describes the pattern, not the severity; severity and prognosis are judged separately (for example by bilirubin and synthetic function).
- A cholestatic or mixed R does not exclude a drug cause; many drugs can produce any of the three patterns.
Evidence & validation
The R-based classification was formalised in international consensus on case definition and phenotype standardisation in DILI (Aithal et al.) and is widely used in hepatology and pharmacovigilance to characterise liver injury.
Frequently asked questions
What does the R factor tell me?
It tells you whether liver injury is predominantly hepatocellular, cholestatic or mixed, based on the relative elevation of ALT versus ALP. This helps direct the differential diagnosis and further work-up.
What R value means hepatocellular injury?
An R of 5 or more indicates a hepatocellular pattern. An R of 2 or less is cholestatic, and values between 2 and 5 are mixed.
Which upper limits of normal should I use?
Use the upper limits of normal from the laboratory that ran the tests, because reference ranges vary between assays and laboratories. Using a generic value can misclassify the pattern.
Does a high R factor mean the injury is severe?
No. The R factor classifies the type of injury, not how severe or dangerous it is. Severity is assessed separately, for example using bilirubin and markers of liver synthetic function.
References
- Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89(6):806–815.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019.
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