Atorvastatin-Associated Liver Injury: Outcome After Statin Rechallenge.

Abstract

<h4>Background</h4>Statin-induced liver injury is frequent and usually not severe. The aim of the present study was to describe the safety of statin rechallenge after atorvastatin-induced liver injury because it is poorly documented.<h4>Methods</h4>Cases of liver injury involving atorvastatin were selected from the French pharmacovigilance database. Inclusion criteria were a documented atorvastatin or any other statin reintroduction and an available follow-up of at least 2 weeks to define negative rechallenge.<h4>Results</h4>Twenty-six cases of atorvastatin liver injury with further statin reintroduction met our criteria. Median time to onset (TTO) of the first episode was 27 days (IQR: 4-43), with a cholestatic pattern in 11 (42.3%) cases, cytolytic in nine (34.6%), and mixed in six (23.1%); severity ranked Grade 2 in 11 (42.3%). Atorvastatin rechallenge was positive in 12 of 16 patients with the same dose (11 of 13) or a reduced dose (1 of 3), and the TTO was shorter (median 11 days). Rechallenge with an alternative statin was performed in 10 patients, of whom two experienced recurrence with rosuvastatin and simvastatin. No recurrence was observed after rechallenge of rosuvastatin in five, pravastatin in two, and simvastatin in one.<h4>Conclusion</h4>Our study evidenced frequent recurrence of drug-induced liver injury after atorvastatin rechallenge, whereas subsequent administration of a hydrophilic statin was well tolerated. By combining our data and published cases, we suggest that rosuvastatin or pravastatin carries the lowest risk of recurrence. Study limitations include a focus solely on atorvastatin, a retrospective design, and potential underreporting to the pharmacovigilance system.