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 7 Council for International Organizations of Medical Sciences scale as an example with items required for causality assessment in a patient with herb induced liver injury by four Indian Ayurvedic herbs
Items for hepatocellular injuryPossible scorePsoralea corylifoliaAcacia catechuEclipta albaVetivexia zizaniodis
Time to onset from the beginning of the herb
5-90 d (rechallenge: 1-15 d)+2
< 5 d or > 90 d (rechallenge: > 15 d)+1+1+1+1+1
Alternative: Time to onset from cessation of the herb
≤ 15 d (except for slowly metabolized herbal chemicals: > 15 d)+1
Course of ALT after cessation of the herb
Percentage difference between ALT peak and N
Decrease ≥ 50% within 8 d+3+3+3+3+3
Decrease ≥ 50% within 30 d+2
No information or continued herbal use0
Decrease ≥ 50% after the 30th day0
Decrease < 50% after the 30th day or recurrent increase-2
Risk factors
Alcohol use (drinks/d: > 2 for women, > 3 for men)+1
No alcohol use (drinks/d: ≤ 2 for women, ≤ 3 for men)00000
Age ≥ 55 yr+1+1+1+1+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-1-1
Concomitant herb or drug known as hepatotoxin and with compatible or suggestive time to onset-2-2-2-2
Concomitant herb or drug with evidence for its role in this case (positive rechallenge or validated test)-3
Search for non herb causes
Group I (6 causes)
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+2+2+2+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+1
Reaction unknown0000
Response to readministration
Doubling of ALT with the herb alone, provided ALT below 5N before reexposure+3
Doubling of ALT with the herb(s) and drug(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 situations0
Total score for each individual herb used by the patient+7+5+5+5