The effect of ezetimibe on NAFLD

Abstract

NAFLD has become the most common liver disorder in countries, where obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome are common. The strong association between these conditions and the risk of cardiovascular disease make treatment crucial. Possible interventions for NAFLD target excess body weight, insulin resistance, inflammation, oxidative stress or intestinal lipid absorption. Administration of combination therapy with a statin plus ezetimibe, associated with lifestyle changes, may represent an effective strategy because of the strong reduction in low-density lipoprotein cholesterol levels. Combination therapy is often more effective, especially when complementary mechanisms of action are involved. Ezetimibe is effective and well tolerated in combination with a number of lipid lowering therapies, including statins, orlistat, and insulin-sensitizing agents. There is strong evidence from preclinical models to supporting the use of ezetimibe in this setting. Larger controlled trials are needed to confirm its effectiveness in patients with NAFLD, to establish the most efficacious combinations and to determine whether treatment can reverse fibrosis.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting > 5% of the liver volume that is not explained by alcohol abuse. It represents a continuum of severity that extends from hepatic steatosis to progressive non-alcoholic steatohepatitis (NASH), which involves also inflammation and fibrosis. NAFLD has become the most common liver disorder in countries, where obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome are common. The prevalence in the general population assessed non-invasively is 20-35%. This number varies widely by geographic location and according to the methodology used for diagnosis [1], [2], [3], [4], [5], [6], [7], [8]. Surveys conducted using more sensitive imaging methods will detect more cases; the highest sensitivity is achieved with biopsy/histology, but this is not feasible for screening purposes due to invasiveness and cost. The strong association between NAFLD and metabolic syndrome (MetS) and obesity, combined with the rapidly increasing rates of these conditions may mean that estimates based on older data underestimate the prevalence. NALFD can occur in the absence of MetS and in lean subjects, but is almost universally associated with insulin resistance [8], [9].

Between 10 and 20% of patients with NAFLD develop non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC) [10]. In the US, as many as two-thirds of obese adults have NAFLD. Approximately 3-15% of patients with NAFLD will progress to NASH-associated cirrhosis.