Table 2.

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

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

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

Total score and resulting causality grading: ≤0, excluded; 1–2, unlikely; 3–5, possible; 6–8, probable; and ≥ 9, highly probable