ABSTRACT
Liver disease caused by drugs or toxins remains a challenge of modern hepatology. This is not
only because the pathogenesis and susceptibility factors for idiosyncratic toxic liver damage are
still poorlyunderstood, but also becauseof the lack of reliable andstandardizedmarkers for toxic
liver damage (1). The diagnosis of drug hepatotoxicity then relies upon circumstantial evidence
of exposure to a potential hepatotoxin as well as the exclusion of other causes of liver injury (2).
This complex process requires a systematic approach and the use of causality assessment
methods, in order to add consistency to the diagnostic process by translating the suspicion
into a quantitative score andbyproviding a frameworkwhich emphasizes the features thatmerit
attention in cases of suspected hepatic adverse reaction. A widely acceptable diagnostic
algorithm would allow unified criteria among clinicians, regulatory agencies, and pharma-
ceutical companies. This issue is critical because the consequences of hepatotoxicity may be
catastrophic, leading to acute liver failure and death. Rapid decisions (including warnings and
withdrawals), especially if based on high accuracy and completeness of data, may prevent
further severe cases. However, none of the available assessment methods has been validated as
yet due to the absence of an accepted “gold standard” for the diagnosis of hepatotoxicity, and
currently neither eliminates nor quantifies uncertainty and has only limited scientific value (3).
DIAGNOSIS IN THE CLINICAL SETTING
