Herb-induced liver injury: An immunological perspective

The application of herbal medicines can be traced back thousands of years, particularly in East Asia and South Asia, and their global popularity has grown steadily over the past decades. Herb-induced liver injury (HILI) has become one of the most challenging drug safety problems globally. The use of the updated RUCAM is essential and is now viewed as the gold standard for assessing causality in cases of HILI and DILI. A growing body of recent epidemiological and clinical evidence shows that immune-mediated hepatotoxicity is a common etiology of herbal medicine-induced liver injury. The activation of various innate immune cells and inflammasomes under natural and inflammatory stress constitutes a key immunological mechanism driving the occurrence of HILI. The discovery of the close association between human leukocyte antigen (HLA) risk alleles and HILI indicates that T-cell mediated adaptive immunity is involved in the pathogenesis of this disease. In addition, the immunomodulatory function of hepatic immune cells modulates host susceptibility to HILI through the action fo co-stilulatory/co-inhibitory molecules and cytokines. The aim of this review is to summerize recent advances in innate and adaptive immunological mechanisms of HILI, and to clarify the mechanisms related to immune regulation in HILI. This review also provides perspectives on future research directions and application of omics approaches for the identification of immunological biomarkers and elucidation of underlying pathogenic mechanisms in HILI.