Structured causality assessment of hepatotoxicity by drugs and dietary supplements (DDS) is a major clinical challenge, since temporal associations as the sole criteria for a valid evaluation are not acceptable. Initially, a clear intuition for an ad hoc evaluation is necessary, but only provisional, and must be followed by a diagnostic algorithm using a pretest, main test and post test. The evaluation is based on a variety of items such as latency period, course of alanine aminotransferase and alkaline phosphatase after DDS discontinuation, risk factors, co-medication, previous information on hepatotoxicity of the DDS, response to rechallenge, and exclusion of other diseases. It is essential that practising and hospital physicians as well as other key health professionals, such as pharmacists, gather all information required for a sound causality assessment, obviating major discussions by expert panels, manufacturers and health agencies in face of scanty and fragmentary data. Because pharmacogenetic alterations may trigger metabolic hepatotoxicity by a few DDS, levels in plasma and urine should be measured and may be helpful for diagnosis. Concomitant genotyping of cytochrome P450 and other enzymes may also be useful in future to minimize the risk of unwanted side-effects, including toxic liver disease elicited by DDS. Hepatotoxicity is a rare, unpredictable and inherent risk associated with the use of various drugs and dietary supplements (DDS) at recommended doses [1][2][3][4][5][6][7][8][9], and several excellent reviews have covered the broad spectrum of DDS hepatotoxicity [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Potentially hepatotoxic drugs include prescribed and over-the-counter medications, which are intensively studied before marketing both experimentally and in several thousands of healthy persons and patients regarding unwanted sideeffects, including hepatotoxicity [24,25]. Nevertheless, rare toxic liver injury cannot be excluded with certainty, as after marketing hepatotoxic reactions occur, for example, in 1:10 000 patients treated for specific diseases [11,18]. Moreover, there is little if any legal regulation of dietary supplements, which comprise a basket of herbs and teas as botanical supplements and weight loss supplements containing herbs and various substances [26][27][28][29][30][31][32]. In face of > 1100 potentially hepatotoxic drugs [17] and the emerging consumption of dietary supplements [13,26], DDS hepatotoxicity has a major impact not only on morbidity, including hospitalization, disability and liver transplantation, but also on mortality, liability and litigation.Early recognition and comprehensive documentation of DDS hepatotoxicity is mandatory at all stages of the disease, but current procedures for efficient, transparent and impartial causality assessment in suspected DDS hepatotoxicity are inadequate. At present, practising and hospital physicians, expert groups, manufacturers and healthcare agencies each use their own individual causality approach, open to dis...
