title: Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing.
abstract: OBJECTIVE
  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 64 years (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 90 days (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 3-4 months after start of therapy. Atorvastatin is mostly associated with cholestatic liver injury whereas hepatocellular injury is more common with simvastatin.
authors: Department of Internal Medicine, Section of Gastroenterology and Hepatology, The National University Hospital, Reykjavik, Iceland. einarsb@landspitali.is
authors: Einar
authors: E
authors: Björnsson
authors: Elin I
authors: EI
authors: Jacobsen
authors: Evangelos
authors: E
authors: Kalaitzakis
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000069059:Atorvastatin; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects; D013548:Sweden; D013997:Time Factors
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin