[Toxic liver disease due to drugs, herbs and dietary supplements: diagnostic approaches]

Toxic liver diseases caused by drugs, herbs and dietary supplements are often recognized late because their hepatotoxic potency is considered to be minimal or non-existent and specific laboratory parameters to definitively establish the diagnosis are lacking. As gold standard for the diagnosis, a positive (unintentional) re-exposure test is considered which is seldom available. A system for evaluation is therefore necessary which takes into account various parameters and defines the grades of causality. By means of a qualitative pre-test with a few questions a screening may be possible as to whether the causality is not probable or not evaluable. Subsequently, a quantitative assessment of the degree of the causality with a main test should be done; this corresponds to the slightly modified and well validated score of the CIOMS (Council for International Organizations of Medical Sciences). The evaluation is achieved using various criteria such as latency period, time between the end of the therapy and begin of the reaction, course of values for the enzyme activities of the liver after cessation of the therapy, risk factors such as age, alcohol consumption and comedication, exclusion of diseases of other organs including chronic liver disease, previous information about hepatotoxicity of the alleged substance and possible results of an unwanted re-exposure. The various answers to these questions are quantitatively assessed, the resulting scores added, and finally an assignment to one of the grades of causality is made. If, on the basis of the main test, there are still doubts about the correct diagnosis, a further test is required to consider the differential diagnosis of additional diseases and chronic liver diseases of other causes. This stepwise approach is essential since ad-hoc decisions regarding causality are not without problems, and other diseases as causes for increased liver values are easily overlooked and not treated adequately in time. By means of this procedure an improvement in the drug safety can be expected, which is fruitful for the patient and helpful to the physician in charge, the health institutions and the drug companies.