The Incidence of Drug- and Herbal and Dietary Supplement-Induced Liver Injury: Preliminary Findings from Gastroenterologist-Based Surveillance in the Population of the State of Delaware.

Background And Aim: The population-based incidence rate of drug-induced liver injury (DILI) in the USA is not known. The Drug-Induced Liver Injury Network (DILIN) accrues cases of hepatotoxicity due to medications and herbal and dietary supplements (HDS) from limited geographical areas. The current analysis was an ancillary study of DILIN aimed at determining the annual incidence of DILI in the USA on a population basis, through surveillance in the state of Delaware.

Methods: At the outset of the study, there were 41 gastroenterologists in the state of Delaware and all agreed to participate in surveillance for DILI, which comprised active reporting of suspected cases to the DILIN. The gastroenterologists underwent training in the diagnosis of DILI and were provided with DILIN inclusion criteria. Only cases that met the DILIN laboratory inclusion criteria in 2014 were included in the incidence calculation, and these patients were invited to participate in the DILIN Prospective Study. The number of suspected cases that met inclusion criteria served as the numerator and the 2014 Delaware adult population as the denominator.

Results: During 2014, 23 patients were identified by the surveillance network, 20 of whom met DILIN laboratory inclusion criteria, leading to an incidence of 2.7 cases of DILI per 100,000 adult residents [95% confidence interval (CI) 1.5-3.9 per 100,000]. Fourteen subjects agreed to participate in the DILIN; six declined. Among enrolled cases, the mean age was 51 years, 57% were women, and 71% were white. Eight cases were attributed to antibiotics (36%) and other drugs (21%) and six to HDS (43%). The pattern of injury was hepatocellular in all HDS cases, but only 50% of conventional drug cases (p = 0.05), which more commonly presented with eosinophilia (p = 0.47) and higher alkaline phosphatase levels (p = 0.05). Half of patients were jaundiced, none developed liver failure, and all recovered without the need for transplantation.

Conclusion: Prospective, gastroenterologist-based surveillance for suspected DILI in Delaware yielded an incidence of 2.7 cases per 100,000 adults in 2014; this is the first prospective estimate of DILI for the USA. Because surveillance was limited to subspecialists, the actual incidence of DILI is likely to be higher. These findings provide a benchmark statistic for the epidemiology of DILI in the United States, to be refined with expansion of the surveillance period.