Table 1.
Council for International Organizations of Medical Sciences scale (CIOMS) for hepatocellular type of injury7
| Items of hepatocellular injury | Score | Result |
|---|---|---|
| 1. Time to onset from the beginning of the drug/herb | ||
| 5–90 days (rechallenge: 1–15 days) | 2 | 2 |
| <5 or >90 days (rechallenge: >15 days | 1 | |
| 2. Course of ALT after cessation of the drug/herb | ||
| Decrease ≥50% within 8 days | 3 | 3 |
| Decrease ≥50% within 30 days | 2 | |
| No information or continued drug/herb use | 0 | |
| Decrease ≥50% after the 30th day | 0 | |
| Decrease <50% after the 30th day or recurrent increase | −2 | |
| 3. Risk factors | ||
| Alcohol use (drinks/day: >2 for women, >3 for men | 1 | 0 |
| Alcohol use (drinks/day: ≤2 for women, ≤3 for men) | 0 | |
| Age ≥55 years | 1 | |
| Age <55 years | 0 | |
| 4. Concomitant drug(s) or herbs(s) | ||
| None or no information | 0 | 0 |
| Concomitant drug or herb with incompatible time to onset | 0 | |
| Concomitant drug or herb with compatible or suggestive time to onset | −1 | |
| Concomitant drug or herb known to be a hepatotoxin and with compatible or suggestive time to onset | −2 | |
| Concomitant drug or herb with evidence for its role in this case (positive rechallenge or validated test) | −3 | |
| 5. Search for non-drug/herb causes | ||
| Group I (6 causes) (tick if negative) | – | 2 |
| Anti-HAV-IgM | – | |
| HBsAg, anti-HBc-IgM, HBV-DNA | – | |
| Anti-HCV, HCV-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 (6 causes) | – | 2 |
| Complications of underlying disease(s) such as sepsis, autoimmune hepatitis, chronic hepatitis B or C, primary biliary cirrhosis or sclerosing cholangitis, genetic liver diseases | – | |
| Infection suggested by PCR and titre change for CMV (anti-CMV-IgM, anti-CMV-IgG) | – | |
| EBV (anti-EBV-IgM, anti-EBV-IgG) | – | |
| HEV (anti-HEV-IgM, anti-HEV-IgG) | – | |
| HSV (anti-HSV-IgM, anti-HSV-IgG) | – | |
| VZV (anti-VZV-IgM, anti-VZV-IgG) | – | |
| All causes groups I and II—reasonably ruled out | 2 | 0 |
| The 6 causes of group I ruled out | 1 | |
| 5 or 4 causes of group I ruled out | 0 | |
| Less than 4 causes of group I ruled out | −2 | |
| Non-drug or herb cause highly probable | −3 | |
| 6. Previous information on hepatotoxicity of the drug/herb | ||
| Reaction labelled in the product characteristics | 2 | |
| Reaction published but unlabelled | 1 | |
| Reaction unknown | 0 | |
| 7. Response to unintentional readministration | ||
| Doubling of ALT with the drug/herb alone, provided ALT below 5N before re-exposure | 3 | |
| Doubling of ALT with the drug(s) and 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 score | 9 | |
Total score and resulting causality grading: ≤0: excluded; 1–2: unlikely; 3–5: possible; 6–8: probable; ≥9: highly probable.
ALT, alanine aminotransferase; AST, Aspartate aminotransferase; CIOMS, Council for International Organizations of Medical Sciences; CMV, cytomegalovirus; 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, MR cholangiography; N, Upper limit of the normal range; VZV, varicella zoster virus.