HEPATOLOGY 2010 A diagnosis of hepatotoxicity must be considered when liver injury is identified in a person taking a prescription drug, herbal, or over-the-counter product, even Abiraterone clinical trial if there is already preexisting liver disease.1-5 Because there is currently no specific marker of drug-induced liver injury (DILI), the diagnosis rests on excluding other conditions that can mimic such injury. The diagnosis is especially difficult when affected persons are taking multiple products, any one of which might be responsible, and because of possible synergism between drugs.1, 6-8 In the traditional diagnostic approach to suspected DILI, which involves

clinical, biochemical, and histological evaluation, www.selleckchem.com/products/Imatinib-Mesylate.html attempts are made to establish the latency between the start of the drug and the onset of injury, its clinical signature, the exclusion of alternate etiologies, evidence of improvement of the liver injury upon drug withdrawal (dechallenge), and the effect of deliberate or inadvertent rechallenge. When performed by an experienced clinician, the assessment is considered by expert opinion. However, even for experts, the diagnosis of DILI can be problematic because of the inherently subjective nature of this approach. Efforts have therefore turned toward developing more objective diagnostic strategies through the creation of specific instruments such as the Roussel-Uclaf Causality Assessment

Method (RUCAM), the Maria and Victorino method, and the Naranjo scale, the last designed to assess all forms of adverse drug reactions.9-13 In a head-to-head comparison of these instruments, RUCAM has been found to perform best for diagnosing hepatotoxicity, but it is cumbersome and therefore is rarely used in clinical

practice. The Drug-Induced Liver Injury Network (DILIN) is a multicenter study whose primary aims are to identify and collect information on bona fide cases of drug-induced liver disease and to obtain serum, DNA, and liver tissue to allow for mechanistic investigation. When the study was being planned, the decision was made to assess causality with both expert opinion and RUCAM. A highly structured expert opinion method was developed that was specifically designed to include standardized terminology and specific methodology, and it is hereafter called find more structured expert opinion. It was hypothesized that this approach may have certain advantages in comparison with RUCAM. This report describes how the expert opinion approach was developed and refined and compares its effectiveness to that of RUCAM.14 ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; CRF, case report form; DCC, data coordinating center; DILI, drug-induced liver injury; DILIN, Drug-Induced Liver Injury Network; INR, international normalized ratio; MAD, maximum absolute difference; RUCAM, Roussel-Uclaf Causality Assessment Method; ULN, upper limit of normal.