Mapping the incidence of drug-induced liver injury worldwide: a systematic review and meta-analysis

Abstract Background: Drug-induced liver injury (DILI), an increasing etiology of liver dysfunction in hepatology, its incidence has been variably reported worldwide. To better understand the disease burden hence make appropriate preventive and treatment strategies, we conducted this meta-analysis from global perspective.Methods: PubMed, EMBASE, Web of Science and Cochrane Library were searched for studies on the incidence of DILI published from inception to Aug 1, 2021. According to the predefined criteria, only population-based studies were included. Incidence was calculated as cases per 100,000 person-years with its confidence interval (CI) using random effects model. Results: A total of 31 studies were included. The overall incidence of DILI was 4.94 (95%CI: 4.05-5.83) per 100,000 person-years. Time-based cumulative meta-analysis suggested that the incidence of DILI had increased over time since 2010. It varied by regions: Asia had the highest incidence, at 17.82 (95%CI: 6.26-29.38) per 100,000 person-years, while America had the lowest, at 1.72 (95%CI: 0.48-2.95) per 100,000 person-years. All studies had a consistent result of higher incidence of DILI in elders; but comparable incidence between male and female (3.42 vs 4.64 per 100,000 person-years). As for the specific implicated drug(s), the incidence of statins induced liver injury was 11.30 (95%CI: 6.48-19.69) per 100,000 person-years, while the incidence among patients using antifungal drugs, antidepressants, paracetamol, antidiabetic, anti-tuberculosis, nonsteroidal anti-inflammatory drugs, anti-thyroid drugs and iron chelator ranged from 0.16 to 180.97 per 100,000 person-years. Conclusions: The incidence of DILI has been increasing since 2010 worldwide, with the highest incidence in Asia. Understanding the epidemiological characteristics of DILI aids in making specific strategies to deal with the emerging health problems.