Table. 1.

RUCAM for the hepatocellular injury of DILI

Item for hepatocellular injury Score Result (azithromycin) Result (tranexamic acid) Result (N-acetyl-cysteine) Result (dihydro-codeine)
1. Time to onset from the beginning of the drug
• 5–90 Days (rechallenge, 1–15 days) +2
• <5 or >90 Days (rechallenge, >15 days) +1
Alternative: time to onset from cessation of the drug
• ≤15 days (except for slowly metabolized chemicals: >15 days) +1
2. Course of ALT after cessation of the drug
Percentage difference between ALT peak and N
• Decrease ≥50% within 8 days +3
• Decrease ≥50% within 30 days +2
• No information or continued drug use 0
• Decrease ≥50% after the 30th day 0
• Decrease <50% after the 30th day or recurrent increase –2
3. Risk factor
• Alcohol use (current drinks/day: >2 for women, >3 for men) +1
• Alcohol use (current drinks/day: ≤2 for women, ≤3 for men) 0
• Age ≥55 years +1
• Age <55 years 0
4. Concomitant drug(s)
• None or no information 0
• Concomitant drug with incompatible time to onset 0
• Concomitant drug with compatible or suggestive time to onset –1
• Concomitant drug known as hepatotoxin and with compatible or suggestive time to onset delete marking right side above –2
• Concomitant drug with evidence for its role in this case (positive rechallenge or validated test) –3
5. Search for alternative causes Tick if negative Tick if not done
Group I (7 causes)
• HAV: anti-HAV-IgM
• Hepatobiliary sonography/color Doppler
• HCV: anti-HCV, HCV-RNA
• HEV: anti-HEV-IgM, anti-HEV-IgG, HEV-RNA
• Hepatobiliary sonography/color Doppler sonography of liver vessels/endosonography/CT/MRC
• Alcoholism (AST/ALT ≥2)
• Acute recent hypotension history (particularly if underlying heart disease)
Group II (5 causes)
• Complications of underlying disease(s) such as sepsis, metastatic malignancy, autoimmune hepatitis, chronic hepatitis B or C, primary biliary cholangitis or sclerosing cholangitis, genetic liver diseases
• Infection suggested by PCR and titer change for
• CMV (anti-CMV-IgM, anti-CMV-IgG)
• EBV (anti-EBV-IgM, anti-EBV-IgG)
• HSV (anti-HSV-IgM, anti-HSV-IgG)
• VZV (anti-VZV-IgM, anti-VZV-IgG)
Evaluation of groups I and II
• All causes-groups I and II—reasonably ruled out +2
• 7 causes of group I ruled out +1
• 6 or 5 causes of group I ruled out 0
• Less than 5 causes of group I ruled out –2
• Alternative cause highly probable –3
6. Previous hepatotoxicity of the drug
• Reaction labelled in the product characteristics +2
• Reaction published but unlabelled +1
• Reaction unknown 0
7. Response to unintentional re-exposure
• Doubling of ALT with the drug alone, provided ALT below 5N before re-exposure +3
• Doubling of ALT with the drug(s) already given at the time of first reaction +1
• Increase of ALT but less than N in the same conditions as for the first administration –2
• Other situations 0
Total score for the case 7 4 4

RUCAM, Roussel Uclaf Causality Assessment Method; DILI, drug-induced liver injury; ALT, alanine aminotransferase; N, upper limit of the normal range; HAV, hepatitis A virus; IgM, immunoglobulin M; HCV, hepatitis C virus; HEV, hepatitis E virus; CT, computer tomography; MRC, magnetic resonance cholangiography; AST, aspartate aminotransferase; PCR, polymerase chain reaction; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HSV, herpes simplex virus; VZV, varicella zoster virus.

Korean J Transplant 2020;34:279~285 https://doi.org/10.4285/kjt.20.0017
© Korean Journal of Transplantation