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      Calc Function

    • Calcs that help predict probability of a diseaseDiagnosis
    • Subcategory of 'Diagnosis' designed to be very sensitiveRule Out
    • Disease is diagnosed: prognosticate to guide treatmentPrognosis
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    Chief Complaint


    Organ System


    Patent Pending

    R Factor for Liver Injury

    Differentiates cholestatic from hepatocellular liver injury, recommended by ACG guidelines.


    Use the first lab values (ALT and ALP) indicating acute liver injury to calculate the R factor.

    When to Use
    Why Use

    Patients with suspected drug induced liver injury (DILI) with abnormal liver chemistries.

    • The pattern of acute liver injury (and therefore the R Factor) can vary throughout the clinical course of the illness.
    • Identifying the pattern of liver injury can guide diagnostic approach to DILI, including appropriate further diagnostic testing necessary to rule out other causes of liver injury.
    • Calculating the R Factor is the first step in calculating the Roussel Uclaf Causality Assessment Method (RUCAM) when determining if liver injury is related to a specific drug.
    • Because the pattern of liver injury can evolve over time, the time point at which liver chemistries are used to calculate the R Factor can alter the final result. It is recommended that the initial liver chemistries suggesting liver injury be used, but ultimately left to the clinician to decide what set of liver chemistries to use when making an assessment.
    • The use of upper limit of normal (ULN) in the equation creates some room for variability. The ULN varies among different laboratories. This calculator uses 40 as the ULN of ALT and 120 as the ULN of ALP.
    • While not validated, the R Factor is widely used and has been incorporated into guideline recommendations for assessing liver injury.
    • Allows clinicians to collectively identify and describe the pattern of liver injury in an objective manner.
    • Allows clinicians suspecting a diagnosis of DILI to formulate an organized diagnostic strategy to rule out other causes of acute liver injury and to narrow the list of possible culprit drugs based on the pattern of liver injury.
    • Recommended by ACG guidelines.


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    R Factor >5 suggests hepatocellular pattern of liver injury.

    • Acute viral hepatitis, ischemic liver injury, Budd-Chiari syndrome, autoimmune hepatitis, and Wilson’s disease (in younger patients) should be ruled out as causes.
    • Commonly used drugs that can cause this pattern of liver injury include: isoniazid, macrolides, nitrofurantoin, minocycline, anti-epileptics, NSAIDs, green tea extract, and inhaled anesthetics.

    R Factor <2 suggests cholestatic pattern of liver injury.

    • Pancreatic malignancy, cholangiocarcinoma, primary malignancy of the gallbladder, choledocholithiasis, sepsis, TPN, heart failure, PSC, and PBC should be ruled out as causes.
    • Commonly used drugs that can cause this pattern of liver injury include: amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, azathioprine, and anabolic steroids.

    R Factor between 2 and 5 suggests a mixed pattern of liver injury.


    Recommendations for workup based on R Factor, adapted from Chalasani 2014.

    Critical Actions

    Though the R Factor does not incorporate coagulopathy (INR) and mental status, these two factors should always be immediately assessed in all cases of acute liver injury to rule out acute liver failure.

    Content Contributors
    • Zaid Tafesh, MD
    About the Creator
    Dr. Christian Bénichou
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    Content Contributors
    • Zaid Tafesh, MD