Drug induced liver injury

Drug induced liver injury (DILI) is a major public health problem which may occur secondary to use of prescription and nonprescription medications or herbal and dietary supplements (HDS). While drug cessation alone is curative in most cases, DILI is the leading causes of acute liver failure in many countries. Some drugs with intrinsic hepatotoxicity cause liver injury in a dose dependent manner in all individuals, but for other idiosyncratic drugs induction of liver injury is largely dose independent and affects only a small fraction of people. Several host genetic and clinical parameters affect an individual's risk for idiosyncratic drug induced liver injury. Practical risk scores are not yet available to preidentify those at risk. In the absence of diagnostic biomarkers, DILI remains a diagnosis of exclusion requiring care providers first to rule out other causes of liver injury. On-line tools, such as LiverTox and DILI RECAM are available to help clinicians assign causality to a specific drug in a case of DILI. HDS manufacturers promote the relative safety of their products, which are poorly regulated, over prescription medications despite a lack of such evidence with regard to liver injury. Indeed, in some countries, HDS are the leading cause of DILI. Cessation of a drug alone typically leads to resolution of any liver injury, but more severe cases may require treatment with N-acetylcysteine or glucocorticoids. Not all cases respond to treatment and DILI is a leading cause of acute liver failure leading to liver transplantation, frequently in response to acetaminophen overdose. Further research to develop both risk scores able to identify preemptively individuals at risk of DILI from specific drugs and early diagnostic biomarkers specific for DILI would greatly reduce DILI morbidity and mortality worldwide.