Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan

Mitsuhiko Aiso; Hajime Takikawa; Keiji Tsuji; Tatehiro Kagawa; Masaaki Watanabe; Atsushi Tanaka; Ken Sato; Shotaro Sakisaka; Yoichi Hiasa; Yoshiyuki Takei; Hiromasa Ohira; Minoru Ayada; Etsuko Hashimoto; Shuichi Kaneko; Yoshiyuki Ueno; Kenji Ohmoto; Akinobu Takaki; Takuji Torimura; Yasushi Matsuzaki; Kazuto Tajiri; Masashi Yoneda; Takayoshi Ito; Naoya Kato; Kenichi Ikejima; Satoshi Mochida; Hiroshi Yasuda; Naoya Sakamoto

doi:10.1111/hepr.13288

Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan

Hepatol Res. 2019 Jan;49(1):105-110. doi: 10.1111/hepr.13288.

Authors

Mitsuhiko Aiso¹, Hajime Takikawa¹, Keiji Tsuji², Tatehiro Kagawa³, Masaaki Watanabe⁴, Atsushi Tanaka¹, Ken Sato⁵, Shotaro Sakisaka⁶, Yoichi Hiasa⁷, Yoshiyuki Takei⁸, Hiromasa Ohira⁹, Minoru Ayada¹⁰, Etsuko Hashimoto¹¹, Shuichi Kaneko¹², Yoshiyuki Ueno¹³, Kenji Ohmoto¹⁴, Akinobu Takaki¹⁵, Takuji Torimura¹⁶, Yasushi Matsuzaki¹⁷, Kazuto Tajiri¹⁸, Masashi Yoneda¹⁹, Takayoshi Ito²⁰, Naoya Kato²¹, Kenichi Ikejima²², Satoshi Mochida²³, Hiroshi Yasuda²⁴, Naoya Sakamoto²⁵

Affiliations

¹ Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
² Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
³ Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
⁴ Department of Gastroenterology, Kitasato University Medical Center, Kitamoto, Japan.
⁵ Department of Gastroenterology and Hepatolpgy, Gunma University, Maebashi, Japan.
⁶ Department of Gastroenterology, Fukuoka University, Fukuoka, Japan.
⁷ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
⁸ Department of Gastroenterology, Mie University, Tsu, Japan.
⁹ Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan.
¹⁰ Department of Internal Medicine, Heiannomori Memorial Hospital, Hamamatsu, Japan.
¹¹ Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
¹² Department of Gastroenterology, Kanazawa University, Kanazawa, Japan.
¹³ Department of Gastroenterology, Yamagata University, Yamagata, Japan.
¹⁴ Department of Gastroenterology, Kurashiki Medical Center, Kurashiki, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
¹⁶ Division of Gastroenterology, Department of Medicine, Kurume University, Kurume, Japan.
¹⁷ Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.
¹⁸ Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
¹⁹ Department of Gastroenterology, Aichi Medical University, Nagakute, Japan.
²⁰ Department of Gastroenterology, Showa University Toyosu Hospital, Tokyo, Japan.
²¹ Department of Gastroenterology, Chiba University, Chiba, Japan.
²² Department of Gastroenterology, Juntendo University, Tokyo, Japan.
²³ Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan.
²⁴ Department of Gastroenterology, St. Marianna Medical University, Kawasaki, Japan.
²⁵ Department of Gastroenterology and Hepatology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.

PMID: 30565816
DOI: 10.1111/hepr.13288

Abstract

Aim: 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.

Methods: 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.

Results: 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".

Conclusions: 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.

Keywords: Chinese herbal medicine; causal drug; dietary supplement; drug-induced liver injury (DILI); drug-induced lymphocyte stimulation test (DLST).