2%)]. Because there is no specific objective marker of Neratinib manufacturer drug-induced liver disease, an accurate diagnosis of hepatotoxicity has constantly been challenging. DILI must always be considered, however, when there is a temporal association between observed liver injury and the receipt

of a drug. The warning signal has been either an acute onset of clinical symptoms (e.g., rash, fever, abdominal pain, or jaundice) or, more commonly, biochemical dysfunction, which includes raised levels of ALT, AST, AP, gamma-glutamyl transpeptidase, and/or serum bilirubin.1, 19, 20 Although these abnormalities strongly suggest liver disease, they are in fact nonspecific indicators and, moreover, do not provide an etiological diagnosis. The use of expert opinion to identify DILI has long been regarded as the gold standard for diagnosing hepatotoxicity, especially when reports come

from well-recognized authorities rather than from an inexperienced occasional observer.2-5, 21, 22 However, because this approach is subjective and lacks defined criteria, a group of international experts convened a meeting under the auspices of the Council for International Organizations of Medical Scientists with the goal of introducing structure and uniformity to the causality process buy LY294002 through the development of highly defined diagnostic criteria for drug-induced liver disease. The meeting was supported by Roussel-Uclaf Pharmaceuticals,

and hence the instrument is called RUCAM. The strategy awards points for seven different domains.10 Other attempts have been made to develop causality instruments with the hope of simplifying the adjudication process,11, 23 but the value of 上海皓元医药股份有限公司 some has been questioned24; this has left RUCAM as the preferred causality instrument. Although used by some experts in the field and often referred to in discussing DILI causality, RUCAM has not been adopted in general clinical practice or, in fact, by most practicing hepatologists and gastroenterologists. The chief reason is that it is a time-consuming process with insufficient and sometimes confusing information on how to score some of the elements of its domains. Nevertheless, during the planning for DILIN, the decision was made to use and compare two approaches for establishing causality: a refined and highly structured expert opinion method and the RUCAM instrument. A direct comparison of the DILIN structured expert opinion and RUCAM revealed that the DILIN process was more likely than RUCAM to generate a score supportive of drug-induced liver disease. Using the DILIN system, reviewers scored 73% of cases (405/557) as definite or highly likely, whereas only 24% of the cases (132/557) were scored as highly probable in the corresponding RUCAM category (Table 6).