Hepatic macrophages in drug-induced liver injury

Abstract

Drug-induced liver injury (DILI) is a major public health concern. Intrinsic DILI, for example, acetaminophen overdose accounts for half of acute liver failure in the United States. However, the most problematic type of DILI affecting drug development and health care is idiosyncratic DILI, which occurs unpredictably in a small population of patients taking the drug and the latency could be several weeks to months. Recent knowledge on the pathogenesis of DILI suggest that hepatic macrophages play a central role in the initiation, progression and restoration stages of DILI, which make hepatic macrophages attractive as therapeutic targets. Hepatic macrophages consist of liver resident macrophages (also known as Kupffer cells, KCs) and infiltrating monocyte-derived macrophages (MoMF). There is a growing appreciation that hepatic macrophage is very plastic, and assumes diverse phenotypes and functions in response to micro-environmental cues. In this review, we will summarize studies on the role of hepatic macrophages in both intrinsic DILI and idiosyncratic DILI, followed by discussing the prognostic and therapeutic potentials of targeting hepatic macrophages and the obstacles in studying hepatic macrophages.