Copyright ©2013 Baishideng Publishing Group Co.
World J Gastroenterol. May 21, 2013; 19(19): 2864-2882
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2864
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) injuryPossible scorePatient’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 use0
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 yr0
Concomitant herbs(s) and drug(s)
None or no information0
Concomitant herb or drug with incompatible time to onset0
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)
HBsAg, anti-HBc-IgM, HBV-DNA
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 out0
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 unknown0
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 situations0
Total score for patient