Drug-Induced Liver Injury

Abstract

Abstract Drug-induced liver injury (DILI) is the most common cause of early termination of clinical drug trials, and it accounts for more than 33% of cases of acute liver failure in clinical practice. DILI can occur through dose-dependent mechanisms, although the majority of cases (>90%) are dose-independent (i.e., idiosyncratic reactions). Important risk factors for the development of DILI are elderly age, polypharmacy, preexisting liver damage, and genetic predisposition. It is very difficult to identify objectively the offending drug as a cause of liver damage; thus current practice commonly relies on expert consensus to identify the offending agent. The most common presentation of the liver damage is an asymptomatic rise in liver enzymes without overt signs of liver failure, although occasional patients may have symptomatic jaundice with subsequent signs of liver failure. Commonly used health and dietary supplements have become the second most common cause of DILI. Classification of DILI into three categories—cholestatic, hepatocellular, or mixed patterns—based on the ratio of serum alanine aminotransferase to alkaline phosphatase levels (called the R ratio) helps narrow the causative agent of liver damage. The management of DILI is dependent on the severity of liver damage and based principally upon early discontinuation of the inciting agent along with supportive care. Transplant-free survival is poor (approximately 40%) in patients who develop acute liver failure. Specific cases may benefit from the use of antidotes if applicable. The most well-known antidote is N-acetylcysteine for acetaminophen toxicity, which accounts for a large number of cases of DILI. Recent studies have proven its usefulness even in cases of nonacetaminophen–associated cases of DILI.