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Cardiovascular Risk Reduction in Patients with Nonalcoholic Fatty Liver Disease: The Potential Role of Ezetimibe

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is widely considered to be the hepatic manifestation of the metabolic syndrome and is closely linked to dyslipidemia, obesity, and insulin resistance. Patients with NAFLD have increased mortality when compared to the general population, primarily related to cardiovascular disease or malignancy. The biologic mechanisms that link NAFLD to cardiovascular disease include expansion of visceral adipose tissue, atherogenic dyslipidemia, impaired insulin signaling, systemic inflammation, and endothelial dysfunction. Currently, there are no approved therapies for NAFLD. It has recently been hypothesized that reducing the delivery of dietary cholesterol using the hypolipidemic agent, ezetimibe, could benefit patients with NAFLD. By potently inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) sterol receptor on intestinal enterocytes and within the liver, ezetimibe blocks exogenous cholesterol absorption and has been shown to improve biochemical markers of NAFLD, improve insulin sensitivity and decrease hepatic steatosis. This review summarizes the clinical and epidemiological evidence for the relationship between NAFLD and cardiovascular risk and examines the potential therapeutic role of ezetimibe.

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Author contributions

Tracey G. Simon was involved in literature review, data interpretation, drafting of the article and critical revision. Raymond T. Chung contributed to interpretation of the data, drafting of the article, critical revision. Kathleen E. Corey contributed to interpretation of the data, drafting of the article, critical revision. Robert Giugliano contributed to interpretation of the data, drafting of the article, critical revision and study supervision

Financial support

Raymond T. Chung and Kathleen E. Corey have received financial support from K24DK078772 and K23DK099422, respectively.

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Authors and Affiliations

  1. Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Tracey G. Simon, Kathleen E. Corey & Raymond T. Chung

  2. Harvard Medical School, Boston, MA, USA

    Tracey G. Simon, Kathleen E. Corey, Raymond T. Chung & Robert Giugliano

  3. Cardiovascular Division, Brigham and Women’s Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA, 02215, USA

    Robert Giugliano

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Correspondence to Robert Giugliano.

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Tracey G. Simon, Kathleen E. Corey and Raymond T. Chung declares that they have no conflict of interest. Robert Giugliano is a member of the TIMI Study Group, which has received research grant support from Amgen, Bristol Myers Squibb and Merck to conduct clinical trials related to lipid therapy. Dr. Giugliano has received honoraria for continuing medical education (CME) lectures and/or consulting from Amgen, Bristol Myers Squibb, Daiichi Sankyo, Merck and Pfizer.

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Simon, T.G., Corey, K.E., Chung, R.T. et al. Cardiovascular Risk Reduction in Patients with Nonalcoholic Fatty Liver Disease: The Potential Role of Ezetimibe. Dig Dis Sci 61, 3425–3435 (2016). https://doi.org/10.1007/s10620-016-4330-z

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