Key points are not available for this paper at this time.
A case report by Hishinuma et al.(1) provides a comprehensive clinicopathological account of vanishing bile duct syndrome (VBDS) following avacopan-containing therapy for microscopic polyangiitis (MPA), culminating in a fatal outcome despite appropriate interventions.The ADVOCATE trial, a pivotal randomized controlled trial, demonstrated that avacopan was generally well tolerated, with serious hepatic adverse events occurring in 5.4% of patients in the avacopan group and 3.7% in the prednisone group; no cases of VBDS were reported in this controlled setting (2).In contrast, recent real-world data have demonstrated a markedly higher incidence of avacopanassociated liver injury in Japanese cohorts than in Western populations.Recent reports show that the incidence of liver injury was 0% in Spain (3), 4.3% in the United States (4), 5.1% in Germany (5), and 16.7%-40.9%in Japan (6-8), indicating a notably higher frequency in Japanese cohorts.These findings suggest that population-specific factors, including age and genetics, may underlie this increased risk in Japan.Patient background has been increasingly recognized as a crucial factor in the risk of avacopan-induced liver injury.Recent Japanese cohort studies have demonstrated that an advanced age, low body mass index (BMI), and early onset of liver dysfunction after avacopan initiation are significantly associated with an increased risk of severe druginduced liver injury (DILI) (7, 8).In the present case, the patient was an 81-year-old man with a BMI of 20.3, features consistent with the identified risk factors (1).In addition, both current and previous studies indicate that DILI in Japan typically presents with certain characteristics such as advanced age, small body size, and myeloperoxidase-anti-
Hishida et al. (Wed,) studied this question.