Original Contribution
An assessment by the Statin Liver Safety Task Force: 2014 update

https://doi.org/10.1016/j.jacl.2014.02.011Get rights and content

Highlights

  • In statin-treated patients, an increase in liver enzymes may be due to different etiologies, which the clinician should consider before assuming the increase in liver enzymes is due to the statin.

  • Mild to modest increases in liver enzymes are not necessarily a contraindication to either initiation or continued use of statins, especially if the clinical presentation and subsequent assessment suggests non-alcoholic fatty liver disease as the reason for the liver enzyme elevation.

  • Patients with elevated liver enzymes are best evaluated using an organized, systematic approach (such as the recommended algorithms in this publication), whether found before initiation of statin therapy, or discovered while treated with statin therapy.

Abstract

In the 2006 Report of the National Lipid Association's Statin Safety Task Force, a panel of experts in hepatology published their findings on specific questions related to the liver blood testing during statin therapy. Among their recommendations was that regulatory agencies reconsider the statin-labeling recommendation at that time, which required post-statin liver enzyme testing. Since then, the Food and Drug Administration altered statin labeling such that unless clinically indicated for other reasons, after a pre-statin therapy baseline evaluation, follow-up liver enzyme testing was not uniformly required after statin initiation. This 2014 report provides an update on interim issues relevant to statins and liver safety. Some of the points discussed include the value of baseline liver enzymes before initiating statin therapy, safety of statin use in patients with nonalcoholic fatty liver disease, potential drug interactions between statins and drugs used to treat hepatitis, the use of statins in liver transplant recipients, and the use of statins in patients with autoimmune liver disease. Finally, this panel provides diagnostic and algorithmic approaches when evaluating statin-treated patients who experience elevations in liver enzymes.

Section snippets

Update on 2006 Statin Safety Task Force report questions

Statins are the most common drugs used in treatment of hypercholesterolemia and among the most commonly used pharmaceuticals in clinical practice. As acknowledged by the hepatologist experts in the 2006 National Lipid Association Statin Safety Task Force Report, statins can increase liver-associated enzymes.6 Table 2 lists the questions and answers addressed by these hepatology experts in 2006 as well as the list of questions and answers from this 2014 Task Force. The following are six

2014 Questions

  • 1.

    Have any unexpected safety concerns arisen since the regulatory recommendation that liver enzymes need not be measured after initiating statin therapy?

ANSWER: No.

STRENGTH OF RECOMMENDATION: A (strong).

QUALITY OF EVIDENCE: Low.

EXPLANATION: The initial 2006 National Lipid Association Statin Safety Task Force Expert Liver Panel recommended that routine liver enzyme testing not be required.6 Subsequently, in 2012, the FDA issued a communication regarding “Important safety label changes to

Recommendations to clinicians

Table 1 provides clinicians a summary of Hy's law, which represents the constellation of liver blood abnormalities with the highest potential for liver toxicity (eg, DILI). Table 2 provides a summary of recommendations made by the 2006 and 2014 Liver Safety Panels. Table 3 provides clinicians an “at-a-glance” summary of illustrative diagnoses for the patient with elevated liver enzymes, with or without statin use. The intended utility of Table 3 is to emphasize that when a statin-treated

References (24)

  • US Food and Drug Administration. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering...
  • A. Reuben et al.

    Drug-induced acute liver failure: results of a U.S. multicenter, prospective study

    Hepatology

    (2010)
  • Cited by (0)

    Disclosures: In the past 12 months, Dr. Harold Bays has served as a consultant and/or speaker to Amarin, Amgen, Astra Zeneca, Bristol Meyers Squibb, Catabasis, Daiichi Sankyo, Eisai, Isis, Merck, Novartis, VIVUS, WPU, and his research site has received research grants from Alere, Amarin, Amgen, Ardea, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, California Raisin Board, Catabasis, Eisai, Elcelyx, Eli Lilly, Esperion, Essentialis, Forest, Gilead, Given, GlaxoSmithKline, High Point Pharmaceuticals LLC, Hoffman LaRoche, Home Access, Janssen, Merck, Metabolex, Micropharma Limited, Necktar, Novartis, Novo Nordisk, Omthera, Orexigen, Pfizer, Pronova, Regeneron, Stratum Nutrition, Takeda, TIMI, Transtech Pharma, Trygg, VIVUS, WPU, and Xoma. Dr. David Cohen reports having received consulting fees from Merck, Aegerion, Dignity Sciences, Genzyme, and Novartis, and has additionally received honoraria from Merck. Dr. Naga Chalasani reports serving as a consultant to Aegerion, Salix, and Lilly; is on the Data and Safety Monitoring Boards of AbbVie and Merck; and his institution has received research grants from Gilead, Intercept, Cumberland, and Enterome. Dr. Stephen Harrison discloses he has received consulting fees/honoraria from Merck, Vertex, and the Chronic Liver Disease Foundation; consulting fees from Nimbus and Genentech; and honoraria from the American Association for Study of Liver Diseases.

    Disclaimer: The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of San Antonio Military Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of Defense or the U.S. Government.

    View full text