Drug-Induced Liver Injury: Pattern Recognition and Future Directions

Abstract

Drug-induced liver injury (DILI) remains a significant clinical challenge and is the leading cause of acute liver failure in most countries. An aging population that uses more medications, a constant influx of newly developed drugs and a growing risk from unfamiliar herbal and dietary supplements will make DILI an increasing part of clinical practice. Currently, the most effective strategy for disease management is rapid identification, withholding the inciting agents, supportive care and having a firm understanding of the expected natural history. There are resources available to aid the clinician, including a new online "textbook" as well as causality assessment tools, but a heightened awareness of risk and the disease's varying phenotypes and good history-taking remain cornerstones to diagnosis. Looking ahead, growing registries of cases, pharmacoepidemiology studies and translational research into the mechanisms of injury may produce better diagnostic tools, markers for risk and disease, and prevention and therapeutics.

Keywords: Diagnosis; Drug induced liver injury; Epidemiology; Hepatotoxicity; Herbal and dietary supplements.

Fig. 1

A native hepatectomy specimen from a 27-year-old male with vanishing bile duct syndrome due to allopurinol. This patient required liver transplantation 10 months after clinical presentation. A histologic section of the liver demonstrates a paucity of interlobular bile ducts. Two portal tracts shown here are devoid of interlobular bile ducts. Overall, approximately two-thirds of the small portal tracts showed bile duct loss (H&E stain, ×200). P, portal tract.

Fig. 2

A liver biopsy from a 69-year-old male patient with a cholestatic pattern of liver injury following administration of trimethoprim-sulfamethoxazole. The hepatic lobules showed predominantly centrizonal hepatocanalicular cholestasis and marked swelling of the perivenular hepatocytes. In this case, there was no evidence of ongoing significant biliary epithelial injury in the portal tracts (inset). The antibiotic had been held for several weeks. A biopsy was conducted for persistent jaundice and pruritus. Eventually, the patient had a full recovery (H&E stain, ×200). C, central vein.

Fig. 3

A liver biopsy from a 55-year-old female who developed a submassive hepatocyte necrosis and dropout 2 to 3 months after starting rosuvastatin. This photomicrograph shows large areas of hepatocyte dropout with multiple aggregates of reactive ceroid-laden macrophages (arrows). No viable hepatocytes are present in this picture (H&E stain, ×200). C, central vein; P, portal tract.