Background In 2009, based on spontaneous reports of serious liver injury the US Food and Drug Administration announced Orlistat may be linked to an increased risk of hepatic events. However, no causal association has been established. The aim of this study was to investigate the association between Orlistat and the incidence of acute liver injury.

Methods This was a self-controlled case-series design using the United Kingdom General Practice Research Database (GPRD) and linked Hospital Episode statistics (HES). People were eligible if they had an incident occurrence of idiopathic acute liver injury with a diagnoses recorded (in GPRD or HES) and were exposed to Orlistat at any time in the observation period. If there was evidence of a known cause for liver disease, such as alcoholism, patients were excluded. Observation time for each patient was divided into strata determined by Orlistat exposure status (30 day strata) and current age. Within-person rate ratios (with 95% confidence intervals) for liver injury were estimated using conditional Poisson regression (Stata 12), comparing exposed with unexposed periods.

Results In the GPRD, between 1999 and 2010, 94,695 people had received at least one prescription for Orlistat, of whom 1,741 had an eligible diagnosis recorded. Of these, 408 people fulfilled eligibility criteria for a definite event (including abnormal liver function test results and a referral). We found a higher incidence of events in the first 30 days of exposure, (compared to unexposed) RR 2.27 (95% CI 1.12 to 4.59) and in the 90 day pre-exposure period RR 1.96 (95% CI 1.35 to 2.85). There was no difference in the incidence of events between 90 days prior and 0–90 days post prescribing, RR 0.78 (95% CI 0.42 to 1.42).

Conclusion This is the first study we are aware of to explore the risk of incident liver injury associated with Orlistat. We found an increased risk of liver events in the 90 days immediately prior to and post first Orlistat prescription, but no difference in risk between the pre and initial exposure periods. This suggests that Orlistat may be initiated during a period of time when adverse liver events are more likely due to poor underlying health, but does not suggest the risk increases with initiation of Orlistat.