Interpreting the DILI R Value

Introduction to DILI R Value

The DILI R value is calculated as (ALT/ULN) ÷ (ALP/ULN) and classifies liver injury patterns: R ≥5 indicates hepatocellular injury, R <2 indicates cholestatic injury, and R between 2-5 indicates mixed injury 1, 2, 3

The formula for the R value is R = (ALT ÷ upper limit of normal for ALT) ÷ (alkaline phosphatase ÷ upper limit of normal for ALP) 1, 2, 3
Laboratory values obtained at the peak of the suspected drug-induced liver injury should be used to calculate the R value 1, 4
The upper limit of normal (ULN) varies among laboratories and may differ by sex and age groups 2

An R value of ≥5 indicates acute hepatocellular injury with predominant elevation of transaminases (ALT/AST), suggesting direct hepatocyte damage from the drug 1, 2, 3
An R value of <2 indicates cholestatic liver injury with predominant elevation of alkaline phosphatase, suggesting bile duct injury or impaired bile flow 1, 2, 3
An R value between 2-5 indicates mixed hepatocellular-cholestatic injury with both transaminase and alkaline phosphatase elevations, showing features of both hepatocyte and bile duct injury 1, 2, 3

For patients with underlying liver disease and baseline abnormal liver tests, the R value should be calculated using the patient's mean baseline values instead of the laboratory's ULN 1, 5, 4
The R value at the peak of suspected DILI should be compared to the patient's baseline R value 1, 5, 4
The utility of the R value in patients with cholestatic liver disease has not been systematically validated and needs to be established 1, 5, 4

Patients with hepatocellular pattern (R ≥5) are at higher risk of severe outcomes, including hepatic failure, and should have repeat testing within 2-5 days to monitor trajectory 1, 7, 8
Patients with cholestatic pattern (R <2) may be indistinguishable from progression of underlying cholestatic liver disease, and repeat testing should be done within 7-10 days 2, 7, 8
Patients with mixed pattern (R 2-5) should have follow-up timing individualized based on severity of elevation and clinical context 7

Patients with chronic liver disease who develop DILI have increased morbidity and mortality compared to those with healthy livers 5, 4, 6, 9
Acute DILI in patients with cholestatic liver diseases should be considered associated with worse outcomes until proven otherwise 5, 4, 6, 9
The R value alone does not establish causality—it only defines the pattern of liver injury 1, 2, 3