Table 6.
Updated Council for International Organizations of Medical Sciences scale for the cholestatic (± hepatocellular) type of injury with items required for causality assessment in herb induced liver injury cases
| Items for cholestatic (± hepatocellular) injury | Possible score | Patient’s score |
| Time to onset from the beginning of the herb | ||
| 5-90 d (rechallenge: 1-90 d) | +2 | |
| < 5 or > 90 d (rechallenge: > 90 d) | +1 | |
| Alternative: Time to onset from cessation of the herb | ||
| ≤ 30 d (except for slowly metabolized herbal chemicals: > 30 d) | +1 | |
| Course of ALP after cessation of the herb | ||
| Percentage difference between ALP peak and N | ||
| Decrease ≥ 50% within 180 d | +2 | |
| Decrease < 50% within 180 d | +1 | |
| No information, persistence, increase, or continued herbal use | 0 | |
| Risk factors | ||
| Alcohol use (drinks/d: > 2 for women, > 3 for men) and pregnancy | +1 | |
| No alcohol use (drinks/d: ≤ 2 for women, ≤ 3 for men) | 0 | |
| Age ≥ 55 yr | +1 | |
| Age < 55 yr | 0 | |
| Concomitant herbs(s) and drug(s) | ||
| None or no information | 0 | |
| Concomitant herb or drug with incompatible time to onset | 0 | |
| Concomitant herb or drug with compatible or suggestive time to onset | -1 | |
| Concomitant herb or drug known as hepatotoxin and with compatible or suggestive time to onset | -2 | |
| Concomitant herb or drug with evidence for its role in this case (positive rechallenge or validated test) | -3 | |
| Search for non drug causes | ||
| Group I (6 causes) | ||
| 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 IU/L) | ||
| Acute recent hypotension history (particularly if underlying heart disease) | ||
| Group II (6 causes) | ||
| Complications of underlying disease(s) | ||
| 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) | ||
| Evaluation of group I and II | ||
| All causes-groups I and II- reasonably ruled out | +2 | |
| 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 herb cause highly probable | -3 | |
| Previous information on hepatotoxicity of the herb | ||
| Reaction labelled in the product characteristics | +2 | |
| Reaction published but unlabelled | +1 | |
| Reaction unknown | 0 | |
| Response to readministration | ||
| Doubling of ALP with the herb alone, provided ALP below 5N before reexposure | +3 | |
| Doubling of ALP with the herb(s) and drug(s) already given at the time of first reaction | +1 | |
| Increase of ALP but less than N in the same conditions as for the first administration | -2 | |
| Other situations | 0 | |
| Total score for patient |
The compilation of individual items is adapted from the updated version of the Council for International Organizations of Medical Sciences (CIOMS) scale[62] and the original CIOMS scale[60]. The above items refer to the cholestatic (± hepatocellular) type of injury, whereas items for the hepatocellular type are presented in Table 5. Regarding risk factor of alcohol use, 1 drink commonly contains about 10 g ethanol[2,3,90]. Total score and resulting causality grading: ≤ 0, excluded; 1-2, unlikely; 3-5, possible; 6-8, probable; ≥ 9, highly probable. ALP: Alkaline phosphatase; N: upper limit of the normal range; HAV: Hepatitis A virus; IgM: Immunoglobulin M; HBsAg: Hepatitis B antigen; HBc: Hepatitis B core; HBV: Hepatitis B virus; HCV: Hepatitis C virus; CT: Computer tomography; MRC: Magnetic resonance cholangiography; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PCR: Polymerase chain reaction; CMV: Cytomegalovirus; EBV: Epstein Barr virus; HEV: Hepatitis E virus; HSV: Herpes simplex virus; IgG: Immunoglobulin G; VZV: Varicella zoster virus.