Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketing

Background & Aims

Limited data exist on drug-induced liver injury (DILI) associated with statins.

Methods

Reports on adverse reactions suspected to be due to statins received by the Swedish Adverse Drug Reactions Advisory Committe 1988–2010 were analyzed. Only cases with >5×upper limit of normal (ULN) in aminotransferases and/or alkaline phosphatase >2×ULN were included.

Results

The most common types of ADRs suspected were DILI in 124/217 (57%) cases. A total of 73/124 (59%) cases had at least possible relationship, median age 64years (57–73), 55% males, whereas 25/124 cases (20%) were excluded due to mild elevations of liver tests and 26 due to unlikely relationship and/or lack of data. A statin-related DILI episode was reported in 1.2/100,000 users. Atorvastatin was implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin (15%), and others. Two patients died of acute liver failure, one underwent liver transplantation and 25 (34%) had jaundice. Three patients were rechallenged with the same statin producing similar patterns of liver injury. The median duration of therapy was 90days (30–120), 120 (39–248) for atorvastatin, and 75 (30–150) for simvastatin (NS). Cholestatic/mixed injury was more common with atorvastatin, 17/30 (56%) than with simvastatin, 7/28 (24%) (p=0.018).

Conclusions

Idiosyncratic liver injury associated with statins is rare but can be severe. After recovery, a similar pattern of liver injury can be reproduced on re-exposure. Most patients experience liver injury 3–4months after start of therapy. Atorvastatin is mostly associated with cholestatic liver injury whereas hepatocellular injury is more common with simvastatin.

Keywords: Hepatoxicity, Statins, Drug-induced liver injury