Landscape of DILI-related adverse drug reaction in China Mainland

Jiabo Wang; Haibo Song; Feilin Ge; Peng Xiong; Jing Jing; Tingting He; Yuming Guo; Zhuo Shi; Chao Zhou; Zixin Han; Yanzhong Han; Ming Niu; Zhaofang Bai; Guangbin Luo; Chuanyong Shen; Xiaohe Xiao

doi:10.1016/j.apsb.2022.04.019

Landscape of DILI-related adverse drug reaction in China Mainland

Acta Pharm Sin B. 2022 Dec;12(12):4424-4431. doi: 10.1016/j.apsb.2022.04.019. Epub 2022 May 6.

Authors

Jiabo Wang^{1

2}, Haibo Song³, Feilin Ge^{1

4}, Peng Xiong¹, Jing Jing¹, Tingting He¹, Yuming Guo¹, Zhuo Shi¹, Chao Zhou¹, Zixin Han¹, Yanzhong Han¹, Ming Niu¹, Zhaofang Bai¹, Guangbin Luo⁵, Chuanyong Shen³, Xiaohe Xiao¹

Affiliations

¹ Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
² School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
³ National Center for ADR Monitoring, Beijing 100022, China.
⁴ Department of Chinese Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁵ School of Medicine, Case Western Reserve University, Cleveland, OH 44122, USA.

Abstract

Drug-induced liver injury (DILI) is a type of bizarre adverse drug reaction (ADR) damaging liver (L-ADR) which may lead to substantial hospitalizations and mortality. Due to the general low incidence, detection of L-ADR remains an unsolved public health challenge. Therefore, we used the data of 6.673 million of ADR reports from January 1st, 2012 to December 31st, 2016 in China National ADR Monitoring System to establish a new database of L-ADR reports for future investigation. Results showed that totally 114,357 ADR reports were retrieved by keywords searching of liver-related injuries from the original heterogeneous system. By cleaning and standardizing the data fields by the dictionary of synonyms and English translation, we resulted 94,593 ADR records reported to liver injury and then created a new database ready for computer mining. The reporting status of L-ADR showed a persistent 1.62-fold change over the past five years. The national population-adjusted reporting numbers of L-ADR manifested an upward trend with age increasing and more evident in men. The annual reporting rate of L-ADR in age group over 80 years old strikingly exceeded the annual DILI incidence rate in general population, despite known underreporting situation in spontaneous ADR reporting system. The percentage of herbal and traditional medicines (H/TM) L-ADR reports in the whole number was 4.5%, while 80.60% of the H/TM reports were new findings. There was great geographical disparity of reported agents, i.e. more cardiovascular and antineoplastic agents were reported in higher socio-demographic index (SDI) regions and more antimicrobials, especially antitubercular agents, were reported in lower SDI regions. In conclusion, this study presented a large-scale, unbiased, unified, and computer-minable L-ADR database for further investigation. Age-, sex- and SDI-related risks of L-ADR incidence warrant to emphasize the precise pharmacovigilance policies within China or other regions in the world.

Keywords: Adverse drug reactions; Database; Drug-induced liver injury; Geographical disparity; Pharmacoepidemiology; Pharmacovigilance; Socio-demographic index; Spontaneous reporting system.