Herbal hepatotoxicity: Challenges and pitfalls of causality assessment methods

Table 4 Details of the various causality assessment methods for herb induced liver injury

Assessed items with specific scores	CIOMS	MV	Naranjo	KL	Ad hoc	DILIN	WHO	Expert opinion
Time frame of latency period (score)	+	+	0	0	0	0	0	0
Time frame of challenge (score)	+	+	0	0	0	0	0	0
Time frame of dechallenge (score)	+	+	0	0	0	0	0	0
Recurrent ALT or ALP increase (score)	+	0	0	0	0	0	0	0
Definition of risk factors (score)	+	0	0	0	0	0	0	0
Verified alternative diagnoses (score)	+	+	0	0	0	0	0	0
Assessed HAV, HBV, HCV (score)	+	+	0	0	0	0	0	0
Assessed CMV, EBV, HSV, VZV (score)	+	+	0	0	0	0	0	0
Liver and biliary tract imaging (score)	+	0	0	0	0	0	0	0
Liver vessel Doppler sonography (score)	+	0	0	0	0	0	0	0
Assessed preexisting diseases (score)	+	0	0	0	0	0	0	0
Evaluated cardiac hepatopathy (score)	+	0	0	0	0	0	0	0
Excluded alternative diagnoses (score)	+	+	+	0	0	0	0	0
Comedication (score)	+	0	+	0	0	0	0	0
Prior known herbal hepatotoxicity (score)	+	+	+	0	0	0	0	0
Searched unintended reexposure (score)	+	+	+	0	0	0	0	0
Defined unintended reexposure (score)	+	+	0	0	0	0	0	0
Unintended reexposure (score)	+	+	0	0	0	0	0	0
Laboratory hepatotoxicity criteria	+	+	0	0	0	+	0	+
Laboratory hepatotoxicity pattern	+	+	0	0	0	+	0	+
Liver specific method	+	+	0	0	0	+	0	+
Structured, liver related method	+	+	0	0	0	+	0	0
Quantitative, liver related method	+	+	0	0	0	0	0	0
Validated method for hepatotoxicity	+	+	0	0	0	0	0	0

Items lacking specific scores were not considered, with the exception of the last six features. The data of the Drug Induced Liver Injury Network method are derived from the report of Rockey et al[102], references for the other methods are found in the text. Latency period indicates time from herb start to symptoms, alternatively to abnormal liver tests. The symbol + shows that this item is present and the symbol 0 indicates lack of this item. ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; HAV: Hepatitis A virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; CMV: Cytomegalovirus; EBV: Epstein Barr virus; HSV: Herpes simplex virus; VZV: Varicella zoster virus; CIOMS: Council for International Organizations of Medical Sciences scale; MV: Maria and Victorino scale; KL: Karch and Lasagna method; DILIN: Drug-Induced Liver Injury Network method; WHO: World Health Organization method.