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Table 2 Updated RUCAM for the nevirapine-induced hepatocellular injury with the total scores for each patient

From: Clinical and genetic factors associated with increased risk of severe liver toxicity in a monocentric cohort of HIV positive patients receiving nevirapine-based antiretroviral therapy

RUCAM items Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8
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 + 2 + 2 + 2 + 2 + 2 + 2 + 2
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)
+ 2 + 2 + 2 + 2 + 2 + 3 + 2 0
3. Risk factors
• Alcohol use (current drinks/d: > 2 for women, > 3 for men) (+ 1)
• Alcohol use (current drinks/d: ≤2 for women, ≤3 for men) (0)
• Age ≥ 55 years (+ 1)
• Age < 55 years (0)
0 0 + 1 0 + 1 + 0 0 0
4. Concomitant drug(s)
• None or no information (0)
• Concomitant drug/herb with incompatible time to onset (0)
• Concomitant drug/herb with compatible or suggestive time to onset (1)
• Concomitant drug/herb known as hepatotoxin and with compatible or suggestive time to onset delete marking right side above (− 2)
• Concomitant drug/herb with evidence for its role in this case (positive rechallenge or validated test) (− 3)
0 0 − 2 0 0 0 0 0
5. Search for alternative causes Tick if negative Tick if not done
Group I (7 causes)
• HAV: Anti-HAV-IgM
• Hepatobiliary sonography / colour Doppler
• HCV: Anti-HCV, HCV-RNA
• HEV: Anti-HEV-IgM, anti-HEV-IgG, HEV-RNA
• Hepatobiliary sonography/colour 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 liverdiseases
• 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)
• The 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)
0 0 0 0 −2 + 1 0 0
6. Previous hepatotoxicity of the drug
• Reaction labelled in the product characteristics (+ 2)
• Reaction published but unlabelled (+ 1)
• Reaction unknown (0)
+ 2 + 2 + 2 + 2 + 2 + 2 + 2 + 2
7. Response to unintentional reexposure
• Doubling of ALT with the drug/herb alone, provided ALT below 5 N before reexposure (+3)
• Doubling of ALT with the drug(s)/herb(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)
0 0 0 0 0 0 0 0
Total + 6 + 6 + 5 + 6 + 5 + 8 + 6 + 4
  1. Abbreviations: pt. Patient, ALT Alanine aminotransferase, AST Aspartate aminotransferase, CMV Cytomegalovirus, CT Computer tomography, EBV Epstein Barr virus, HAV Hepatitis A virus, HBc Hepatitis B core, HBsAg Hepatitis B antigen, HBV Hepatitis B virus, HCV Hepatitis C virus, HEV Hepatitis E virus, HSV Herpes simplex virus, MRC Magnetic resonance cholangiography, N upper limit of the normal range, RUCAM Roussel Uclaf Causality Assessment Method, VZV Varicella zoster virus
  2. Total score and resulting causality grading: ≤0, excluded; 1–2, unlikely; 3–5, possible; 6–8, probable; and ≥ 9, highly probable