Review article: drug-induced liver injury - its pathophysiology and evolving diagnostic tools

Background Drug-induced liver injury (DILI) is a significant cause of morbidity and mortality accounting for at least 13% of acute liver failure cases in the US. It is the leading cause of acute liver failure among patients referred for liver transplantation and the most common reason that drugs in development do not obtain FDA approval. The incidence of DILI has been reported to be one in 10 000 to one in 100 000 patients; however, the actual incidence is probably higher due in part to the difficulty of diagnosis. Aim To present a review of the current literature on DILI with a focus on its pathophysiology and evolving diagnostic modalities. Methods A PubMed literature search was conducted using the terms 'drug induced liver injury', 'pathophysiology', 'causality', 'diagnosis', 'toxicogenomics' and 'pharmacogenetics'. Results Drug-induced liver injury is an area of ongoing research. From the time it was first recognised, our understanding of the pathophysiology, its classification, diagnosis and reporting by established national networks continues to challenge and evolve. Metabonomics, pharmacogenetics, proteomics and transcriptomics are more recent areas of study that have been applied to further the understanding of DILI. Conclusions Despite recent advances in our understanding of drug-induced liver injury, many aspects of its pathophysiology and clinical impact remain unclear. In addition, genomic-based studies are evolving concepts, which undoubtedly continue to contribute to our understanding of the underlying mechanisms of drug-induced liver injury. Aliment Pharmacol Ther 2011; 34: 11-20