Causality assessment in drug-induced hepatotoxicity

Drugs are currently an important cause of liver disease, ranked as the most frequent reason for acute liver failure. Despite recent advances in knowledge of the mechanisms implicated in drug-induced hepatocellular damage and cholestasis, as well as the identification of several risk factors, the diagnosis of hepatotoxicity remains a difficult task because specific tests are not available. In a step-by-step approach, the incrimination of a drug in liver symptoms requires a high degree of suspicion on the part of the physician, temporal eligibility, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favour a toxic aetiology. Ultimately, the use of diagnostic algorithms may add consistency to the diagnostic process either by translating the suspicion into a quantitative score or by providing a framework that emphasises the features that merit attention in cases of suspected hepatic adverse reactions.