Kampo medicine inducing drug-induced liver injury: A case report and systematic review.

Kampo medicine, comprising various conventional crude drug products, poses challenges in identifying adverse event causality. We present a case of severe liver injury following the administration of Saibokuto and attempted to identify the likely causative crude drug inducing liver injury through a systematic literature review. A 29-year-old woman developed severe liver injury approximately two months after Saibokuto administration, necessitating steroid pulse therapy for recovery. The literature search was conducted on February 15, 2023 in Japan. Using PubMed and the "Igaku Chuo Zasshi (ICHUSHI) database," two individuals independently selected studies published between January 1997 and February 15, 2023. The search focused on studies involving human subjects, published in either English or Japanese, and specifically investigated Kampo medicines categorized as over-the-counter or prescription drugs suspected as causative agents of drug-induced liver injury (DILI). Studies on health supplements, discontinued Kampo medicines, and autoimmune hepatitis, were excluded. As it is ethically impossible to rechallenge drugs that cause liver injury, this review primarily relied on case report literature. Through the review, 37 cases (men/women: 12/25, including present case) were analyzed, including 32 reports (36 cases) from 3,055 studies that met the inclusion criteria. Notably, 65.9% of cases were associated with Scutellariae radix, with onset occurring within 45 (1-730) days and recovery within 35 (7-184) days. Our case study and literature review underscore a prevalent association between liver injury and Kampo medicines containing Scutellariae radix. Vigilant liver function monitoring, particularly within the first 2 months of administration, is recommended, especially for formulations containing Scutellariae radix.