R Factor for Liver Injury
Why Use
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 .
When to Use
Patients with suspected drug induced liver injury (DILI) with abnormal liver chemistries.
Formula
Pearls / Pitfalls
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.
Management
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.
Advice
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.
More Information
Interpretation: R Factor Injury type Recommended 1st line tests* >5 Hepatocellular Acute viral hepatitis serologies, HCV RNA and autoimmune hepatitis serologies, imaging studies (e.g. abdominal ultrasound) 2–5 Mixed Acute viral hepatitis serologies, HCV RNA and autoimmune hepatitis serologies, imaging studies (e.g. abdominal ultrasound) <2 Cholestatic Imaging studies (e.g. abdominal ultrasound) *From Chalasani 2014 .