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

Table 2 Council for International Organizations of Medical Sciences scale for the cholestatic or mixed type of injury and cholestatic or mixed type of injury in drug induced liver injury and herb induced liver injury cases

Items for cholestatic or mixed injury	Score	Result
1 Time to onset from the beginning of the drug/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 drug/herb
≤ 30 d (except for slowly metabolized chemicals: > 30 d)	1	-
2 Course of ALP after cessation of the drug/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 drug/herb use	0	-
3 Risk factors
Alcohol use (drinks/d: > 2 for women, > 3 for men) or pregnancy	1	-
Alcohol use (drinks/d: ≤ 2 for women, ≤ 3 for men)	0	-
Age ≥ 55 yr	1	-
Age < 55 yr	0	-
4 Concomitant drug(s) or herbs(s)
None or no information	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 as 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	Tick if negative	-
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 titer 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 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 ALP with the drug/herb alone, provided ALP below 5N before reexposure	3	-
Doubling of ALP with the drug(s) and herb(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 CIOMS scale presented in this table is designed specifically for the cholestatic or mixed type of liver injury rather than for the hepatocellular type, which differs in a few items and is presented separately in Table 1. Additional details and abbreviations are provided in the legend of Table 1. Abbreviation: ALP, Alkaline phosphatase. Total score with resulting causality grading: ≤ 0, excluded; 1-2, unlikely; 3-5, possible; 6-8, probable; ≥ 9, highly probable.