Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

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 different Indian Ayurvedic herbs

Items for hepatocellular injury	Possible score	Psoralea corylifolia	Acacia catechu	Eclipta alba	Vetivexia zizaniodis
1 Time to onset from the beginning of the herb 5-90 d (rechallenge: 1-15 d)	2
< 5 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
2 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 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/d: > 2 for women, > 3 for men)	1
Alcohol use (drinks/d: ≤ 2 for women, ≤ 3 for men)	0	0	0	0	0
Age ≥ 55 yr	1	1	1	1	1
Age < 55 yr	0
4 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	-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
5 Search for non herb 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)		-	-	-	-
Acute recent hypotension history (particularly if underlying heart disease)		-	-	-	-
Group II (6 causes)
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)		-	-	-	-
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 out	0
Less than 4 causes of group I ruled out	-2
Non herb cause highly probable	-3
6 Previous information on hepatotoxicity of the herb
Reaction labelled in the product characteristics	2
Reaction published but unlabelled	1	1
Reaction unknown	0		0	0	0
7 Response to unintentional 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 situations	0
Total score for each individual herb used by the patient		7	5	5	5

The data of the patient with severe hepatotoxicity by four different Indian Ayurvedic herbs are derived from a published report[30], using the CIOMS scale for the hepatocellular type of liver injury (Table 1). The symbol of - signifies that this particular item has been evaluated and no abnormality was found. For the four herbs, the total score was either +7 (probable causality) or +5 (possible causality). Abbreviations see legend to Table 1.