Aiso Mitsuhiko, Takikawa Hajime, Tsuji Keiji, Kagawa Tatehiro, Watanabe Masaaki, Tanaka Atsushi, Sato Ken, Sakisaka Shotaro, Hiasa Yoichi, Takei Yoshiyuki, Ohira Hiromasa, Ayada Minoru, Hashimoto Etsuko, Kaneko Shuichi, Ueno Yoshiyuki, Ohmoto Kenji, Takaki Akinobu, Torimura Takuji, Matsuzaki Yasushi, Tajiri Kazuto, Yoneda Masashi, Ito Takayoshi, Kato Naoya, Ikejima Kenichi, Mochida Satoshi, Yasuda Hiroshi, Sakamoto Naoya
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
Hepatol Res. 2019 Jan;49(1):105-110. doi: 10.1111/hepr.13288.
In order to know the present status of drug-induced liver injury (DILI) in Japan, we present the data of prospectively collected DILI cases between 2010 and 2018 from 27 hospitals.
Drug-induced liver injury cases diagnosed by DILI experts from 27 hospitals all over Japan have been prospectively collected since 2010. Alanine aminotransferase level ≥150 U/L and/or alkaline phosphatase ≥2× upper limit of normal were inclusion criteria.
In total, data of 307 cases (125 male and 182 female individuals) aged between 17 and 86 years old were collected. The types of liver injury were as follows: 64% hepatocellular type, 20% mixed type, and 16% cholestatic type. A drug-induced lymphocyte stimulation test was carried out in 59% of cases, and was positive in 48% and semipositive in 3% of cases. Eosinophilia ≥6% was observed in 27% of cases. Fifty-three percent of DILI cases occurred within 30 days and 79% of DILI cases occurred within 90 days after starting drug administration. By the diagnostic scale of the Digestive Disease Week (DDW)-Japan 2004 workshop, 93.8% of cases were diagnosed as "highly probable", and 5.9% as "possible".
Japanese DILI patients are somewhat different from those of Europe and North America. The diagnostic scale of the DDW-Japan 2004 workshop has been used in Japan. However, there are many issues to improve the causality assessment of DILI that we must investigate in the future. It is critical to elucidate the mechanisms of drug metabolism and the pathophysiology of liver injury by various drugs to prevent DILI.
为了解日本药物性肝损伤（DILI）的现状，我们展示了2010年至2018年期间从27家医院前瞻性收集的DILI病例数据。
自2010年起，前瞻性收集了日本各地27家医院的DILI专家诊断的药物性肝损伤病例。纳入标准为丙氨酸转氨酶水平≥150 U/L和/或碱性磷酸酶≥正常上限的2倍。
共收集了307例病例（男性125例，女性182例）的数据，年龄在17至86岁之间。肝损伤类型如下：肝细胞型64%，混合型20%，胆汁淤积型16%。59%的病例进行了药物诱导淋巴细胞刺激试验，其中48%呈阳性，3%呈半阳性。27%的病例观察到嗜酸性粒细胞增多≥6%。53%的DILI病例在开始用药后30天内发生，79%的DILI病例在开始用药后90天内发生。根据2004年日本消化疾病周（DDW）研讨会的诊断标准，93.8%的病例被诊断为“高度可能”，5.9%为“可能”。
日本的DILI患者与欧洲和北美的患者有所不同。日本使用了2004年日本消化疾病周研讨会的诊断标准。然而，在DILI因果关系评估方面仍有许多问题需要改进，我们未来必须进行研究。阐明药物代谢机制和各种药物所致肝损伤的病理生理学对于预防DILI至关重要。
