Drug-induced liver injury: a comprehensive review

Abstract

Drug-induced liver injury (DILI) remains a challenge in clinical practice and is still a diagnosis of exclusion. Although it has a low incidence amongst the general population, DILI accounts for most cases of acute liver failure with a fatality rate of up to 50%. While multiple mechanisms of DILI have been postulated, there is no clear causal relationship between drugs, risk factors and mechanisms of DILI. Current best practice relies on a combination of high clinical suspicion, thorough clinical history of risk factors and timeline, and extensive hepatological investigations as supported by the international Roussel Uclaf Causality Assessment Method criteria, the latter considered a key diagnostic algorithm for DILI. This review focuses on DILI classification, risk factors, clinical evaluation, future biomarkers and management, with the aim of facilitating physicians to correctly identify DILI early in presentation.

Keywords: DILI; RUCAM; acute hepatitis; acute liver failure; acute liver injury; drug-induced liver injury.

Figure 1.

Classification of DILI. *Medications known to cause hepatocellular, cholestatic or mixed pattern of liver injury. DILI, drug-induced liver injury.

Figure 2.

Clinical algorithm for suspected DILI. ALP, alkaline phosphatase; ALT, alanine transaminase; CMV, cytomegalovirus; DILI, drug-induced liver injury; EBV, Epstein-Barr virus; HAV, Hepatitis A virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HEV, Hepatitis E virus; HSV, herpes simplex virus; KCC, King College Criteria; LT, liver transplantation; MELD, Model For End-Stage Liver Disease; OTC, Over-the-counter; RUCAM, Roussel Uclaf Causality Assessment Method; ULN, upper limit of normal.