Spectrum of statin hepatotoxicity: Experience of the drug-induced liver injury network


  • Potential conflict of interest: M.W. Russo does speaking and teaching for Gilead Sciences, Salix, Janssen, and Vertex; he receives research support from Merck, Vertex, and Salix. R.J. Fontana is a consultant for GlaxoSmithKline and receives research support from Vertex Pharmaceutical, Gilead and Bristol-Myers Squibb. N. Chalasani is a consultant for Aegerion, Merck, AbbVie, Salix, Lilly and Nimbus and receives research support from Cumberland, Gilead Sciences, Intercept Pharmaceuticals, and Galectin. H.L. Bonkovsky receives research support and is a consultant for Clinuval, Alnylam, Recordati, Vertex Pharmaceuticals, American Porphyria Foundation, and Iron Disorders Institute. The other authors declare no conflicts of interest to report.

  • DILIN is supported by the National Institute of Diabetes and Digestive and Kidney Diseases under the following cooperative agreements: 1UO1DK065201, 1UO1DK065193, 1UO1DKO65184, 1UO1DK065211, 1UO1DK065238, and 1UO1DK06F5176. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute.


The HMG-CoA reductase inhibitors (statins) are widely prescribed for patients with hyperlipidemia and are generally well tolerated. Mild elevations in serum aminotransferases arise in up to 3% of treated patients, but clinically apparent drug-induced liver injury is rare. The aim of this study is to report the presenting features and outcomes of 22 patients with clinically apparent liver injury due to statins. Among 1,188 cases of drug-induced liver injury enrolled between 2004 and 2012 in a prospective registry by the U.S. Drug Induced Liver Injury Network, 22 were attributed to a statin. All patients were evaluated in a standard fashion and followed for at least 6 months after onset. The median age was 60 years (range 41-80), and 15 (68%) were female. The latency to onset of liver injury ranged from 34 days to 10 years (median = 155 days). Median peak levels were alanine aminotransferase 892 U/L, alkaline phosphatase 358 U/L, and total bilirubin 6.1 mg/dL. Nine patients presented with cholestatic hepatitis and 12 patients presented with hepatocellular injury, of which six had an autoimmune phenotype. Nine patients were hospitalized, four developed evidence of hepatic failure, and one died. All commonly used statins were implicated. Four patients developed chronic liver injury, of which three had an autoimmune phenotype of liver injury. Conclusion: Drug-induced liver injury from statins is rare and characterized by variable patterns of injury, a range of latencies to onset, autoimmune features in some cases, and persistent or chronic injury in 18% of patients, most of whom have an autoimmune phenotype. (Hepatology 2014;60:679–686)