Table 3.
Roussel Uclaf Causality Assessment Method for drug-induced liver injury/herb-induced liver injury hepatocellular injury*
| Points | Case report | ||
| Time to onset from beginning of drug/herb | 5–90 days (re-challenge: 1–15 days) | 2 | |
| <5 or >90 days (re-challenge: >15 days) | 1 | X | |
| Time to onset from cessation of drug/herb | ≤15 days (except for slowly metabolised chemicals >15 days) | 1 | |
| Course of ALT after cessation of drug/herb (% difference between ALT peak and N) |
Decrease ≥50% within 8 days | 3 | |
| Decrease ≥50% within 30 days | 2 | X | |
| No information or continued drug use | 0 | ||
| Decrease ≥50% after the 30th day | 0 | ||
| Decrease <50% after the 30th day or recurrent increase | −2 | ||
| Risk factors | Alcohol use—presence | 1 | |
| Alcohol use—absence | 0 | X | |
| Age ≥55 years | 1 | X | |
| Age <55 years | 0 | ||
| Concomitant drug(s)/herb(s) | None or no information | 0 | |
| Concomitant drug/herb with incompatible time to onset | 0 | X | |
| 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 | −2 | ||
| Concomitant drug/herb with evidence for its role in this case (positive rechallenge or validated test) | −3 | ||
| Search for alternative causes† | All causes reasonably ruled out (group I and II) | 2 | X |
| Six causes of group I ruled out | 1 | ||
| 4–5 causes of group I ruled out | 0 | ||
| <4 causes of group I ruled out | −2 | ||
| Alternative cause highly probable | −3 | ||
| Previous hepatotoxicity of drug/herb | Reaction labelled in the product characteristics | 2 | |
| Reaction published but unlabelled | 1 | X | |
| Reaction unknown | 0 | ||
| Response to unintended re-exposure | Doubling of ALT with drug/herb alone, (if ALT <5N before re-exposure) | 3 | |
| Doubling of ALT with drug/herb already given at time of first reaction | 1 | ||
| Increase of ALT but <5N in the same conditions as for first administration | −2 | ||
| Other situations | 0 | ||
| Total | 7‡ |
*Adapted from Danan and Benichou.22
†Group I causes: HAV, HBV, HCV, biliary obstruction (imaging), alcoholism, acute recent hypotension.
Group II causes: complications of underlying disease (eg, sepsis), CMV, EBV, HSV.
‡≤0, excluded causality; 1 – 2, unlikely; 3 – 5, possible; 6 – 8, probable; ≥ 9, highly probable.
ALT, alanine transaminase; CMV, cytomegalovirus; EBV; Epstein Barr virus; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HSV, herpes simplex virus.