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

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 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)

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)

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)

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 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)

Total