Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink

OBJECTIVE To measure the association between orlistat and acute liver injury. DESIGN Self controlled case series study. SETTING Population based primary care setting, United Kingdom. PARTICIPANTS 94,695 patients receiving orlistat and registered in the UK Clinical Practice Research Datalink and linked with Hospital Episode Statistics data between 1999 and 2011. MAIN OUTCOME MEASURE Relative incidence of acute liver injury comparing periods when patients were receiving orlistat with periods of non-usage. RESULTS Among 94,695 patients who received orlistat, 988 cases of acute liver injury were identified, with 335 confirmed as definite cases and 653 as probable cases. For all cases an increased incidence of liver injury was detected during the 90 day period before orlistat was first started, with an incidence rate ratio of 1.50 (95% confidence interval 1.10 to 2.06). The incidence remained raised during the first 30 days of treatment (2.21, 1.43 to 3.42), before returning to baseline levels with prolonged treatment. When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of liver injury was not increased (1.02, 0.67 to 1.56). An analysis restricted to definite cases showed no evidence of an increased risk of liver injury during treatment. CONCLUSION The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug.