A retrospective case-controlled cohort study of inpatient drug induced liver injury: the RIDDLE study.

Background: Identification of risk factors for drug-induced liver injury (DILI) has been hindered by the unpredictable incidence and idiosyncratic nature of DILI. The aim of this study was to identify characteristic host risk factors for DILI.

Methods: A retrospective cohort study was performed examining all patients admitted with a diagnosis of DILI over a 5.5-year period. Cases were compared to a control group non-exposed to DILI using propensity score-derived inverse probability weights. Patients with DILI due to alcohol or paracetamol were excluded from analysis.

Results: Seventy-two cases of DILI admitted to hospital were identified. Antimicrobials caused 56.9% of cases, with amoxicillin-clavulanate the single most common agent, responsible for 13.9% of cases. DILI cohort median age (50.2±36 years) was significantly younger than controls (65.0±38 years) (P<0.001). Pre-existing chronic liver disease (OR, 3.44; 95% CI, 1.38-8.59; P=0.008), length of stay (P<0.001) and in-hospital death (P=0.009) were more likely to be associated with DILI cases. There was no correlation with sex (OR male, 0.92; 95% CI, 0.50-1.67; P=0.78), presence of comorbid autoimmune disease (OR, 1.44; 95% CI, 0.68-3.05; P=0.35), past drug allergies (OR, 1.71; 95% CI, 0.92-3.16; P=0.09), or atopy (OR, 0.87; 95% CI, 0.42-1.82; P=0.72).

Conclusions: Younger age and presence of chronic liver disease were associated with an admission with DILI; however, it remains difficult to predict the population at risk of DILI on clinical grounds and putative risk factors such as female gender, and history of other drug allergies and autoimmunity, were not demonstrated in this study.