Drug-Induced Liver Injury: Highlights of the Recent Literature

Abstract

Drug-induced liver injury (DILI), herbal-induced liver injury, and herbal and dietary supplement (HDS)-induced liver injury are an important aspect of drug safety. Knowledge regarding responsible drugs, mechanisms, risk factors, and the diagnostic tools to detect liver injury have continued to grow in the past year. This review highlights what we considered the most significant publications from among more than 1800 articles relating to liver injury from medications, herbal products, and dietary supplements in 2017 and 2018. The US Drug-Induced Liver Injury Network (DILIN) prospective study highlighted several areas of ongoing study, including the potential utility of human leukocyte antigens and microRNAs as DILI risk factors and new data on racial differences, the role of alcohol consumption, factors associated with prognosis, and updates on the clinical signatures of autoimmune DILI, thiopurines, and HDS agents. Novel data were also generated from the Spanish and Latin American DILI registries as well as from Chinese and Korean case series. A few new agents causing DILI were added to the growing list in the past 2 years, including sodium-glucose co-transporter-2 inhibitors, as were new aspects of chemotherapy-associated liver injury. A number of cases reported previously described hepatotoxins confirmed via the Roussel Uclaf Causality Assessment Method (RUCAM; e.g., norethisterone, methylprednisolone, glatiramer acetate) and/or the DILIN method (e.g., celecoxib, dimethyl fumarate). Additionally, much work centered on elucidating the pathophysiology of DILI, including the importance of bile salt export pumps and immune-mediated mechanisms. Finally, it must be noted that, while hundreds of new studies described DILI in 2017-2018, the quality of such reports must always be addressed. Björnsson reminds us to remain very critical of the data when addressing the future utility of a study, which is why it is so important to adhere to a standardized method such as RUCAM when determining DILI causality. While drug-induced hepatotoxicity remains a diagnosis of exclusion, the diverse array of publications that appeared in 2017 and 2018 provided important advances in our understanding of DILI, paving the way for our improved ability to make a more definitive diagnosis and risk assessment.