Lesser celandine (pilewort) induced acute toxic liver injury: The first case report worldwide

Table 1 Score of the presented patient according to Council for International Organizations of Medical Sciences Scale

Items for hepatocellular injury	Score	Result of the presented case1
1 Time to onset from the beginning of the drug/herb
5-90 d (rechallenge: 1-15 d)	2	+
< 5 or > 90 d (rechallenge: > 15 d)	1	-
Alternative: Time to onset from cessation of the drug/herb
≤ 15 d (except for slowly metabolized chemicals: > 15 d)	1	-
2 Course of ALT after cessation of the drug/herb
Percentage difference between ALT peak and N
Decrease ≥ 50% within 8 d	3	+
Decrease ≥ 50% within 30 d	2	-
No information or continued drug/herb 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	+
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	“+” 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 ALT with the drug/herb alone, provided ALT below 5N before reexposure	3	-
Doubling of ALT with the drug(s) and herb(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		7

¹The score of the patient for each 7 item for hepatocellular injury was indicated as “+” in the correspondent cell. HBV: Hepatitis B virus; HCV: Hepatitis C virus.