Liver and Statins: A Critical Appraisal of the Evidence

Curr Med Chem. 2018;25(42):5835-5846. doi: 10.2174/0929867325666180327095441.

Abstract

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion-transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in the development of clinically relevant adverse events. Finally, we appraise the evidence for and against the use of statins in metabolic syndrome and in HCV-infected patients, in terms of their safety and efficacy in cardiovascular events.

Keywords: HCV; MetS; Statins; genetic susceptibility; liver damage; single nucleotide polymorphisms (SNPs)..

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / pathology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • Hepatitis C / complications
  • Hepatitis C / pathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Organic Anion Transporters / genetics

Substances

  • ATP-Binding Cassette Transporters
  • HLA Antigens
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Organic Anion Transporters
  • Cytochrome P-450 Enzyme System