Role of ezetimibe in non-alcoholic fatty liver disease

Filippatos, Theodosios D.; Elisaf, Moses

doi:10.4254/wjh.v3.i10.265

Cited by 25 publications

(16 citation statements)

References 23 publications

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“…In addition, reactive oxygen species (ROS), endotoxins, and inflammatory cytokines result in the disease development [7]. It is also well known that several stressors like cigarette smoke, pollutants, diabetes, hypertension, and hypercholesterolemia are all risk factors to the disease [8, 9]. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased free fatty acids (FFAs), which causes lipotoxicity, impairs endothelium-dependent vasodilatation, and increases oxidative stresses.…”

Section: Introductionmentioning

confidence: 99%

Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease

2013

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Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver pathologies and is associated with obesity and the metabolic syndrome, which represents a range of fatty liver diseases associated with an increased risk of type 2 diabetes. Molecular mechanisms underlying how to make transition from simple fatty liver to nonalcoholic steatohepatitis (NASH) are not well understood. However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. The molecular mechanisms contributing to the diseases are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies for a condition.

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Section: Introductionmentioning

confidence: 99%

Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease

2013

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“…This protein is expressed by both enterocytes and hepatocytes. It was suggested that ezetimibe may be useful for the management of NAFLD by inhibiting hepatic cholesterol accumulation [45] . This can be better achieved by combinations of ezetimibe with drugs facilitating weight loss or enhancing insulin sensitivity [45] .…”

Section: Introductionmentioning

confidence: 99%

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

131

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Non-alcoholic fatty liver disease (NAFLD) is a common health problem with a high mortality burden due to its liver-and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). Impaired hepatic fatty acid (FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors (PPARs) are involved in lipid and glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis. These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet, T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

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“…Our patient could not receive a statin due to abnormal liver function. He was instead started on ezetimibe because of its LDL-C lowering effect particularly in the setting of advanced liver fibrosis [4] . Another option for reducing LDL-C in our patient was by LDL apheresis, a technique that has proven to significantly reduce low-density lipoprotein cholesterol in patients with severe hypercholesterolemia and slow the progression of atherosclerosis [5] .…”

Section: Discussionmentioning

confidence: 99%

Severe hypercholesterolemia effectively lowered with hemodialysis: a case report

Bakinde

Ekong

Olayeye

et al. 2015

CRCP

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Background: Hypercholesterolemia is a known risk factor for cardiovascular morbidity and mortality. Reviews of current literature suggest a linear correlation between the level of low density lipoprotein cholesterol (LDL-C) and the risk of cardiovascular disease. There are no guidelines that specifically address the management of severe hypercholesterolemia related to an underlying pathology or that observed in familial hypercholesterolemia. Case report:A 49-year-old African American man presented with painless jaundice, generalized itching, and a 30 lbs weight loss in three months. Multiple xanthoma like lesions were noted on his arms. His hepatic panel was normal. His levels of total cholesterol and low density lipoprotein cholesterol were elevated to more than 1,000 mg/dl each. Serum alkaline phosphatase, total bilirubin, and direct bilirubin were elevated at 1,715 U/L, 7.2 mg/dl, and 4.5 mg/dl, respectively. The level of high density lipoprotein cholesterol was undetectable. Anti-mitochondrial antibodies and hepatitis serologies were negative. There was no clinical evidence to suggest familial hypercholesterolemia. Imaging studies of his abdomen were negative for hepatic biliary dilation. A liver biopsy revealed stage 3 fibrosis. His severe hypercholesterolemia was treated with ezetimibe, since statin was contraindicated in this case. In addition to liver fibrosis, the patient developed renal failure that required intermittent hemodialysis. His LDL cholesterol (LDL-C) and total cholesterol (TC) levels trended down with an absolute reduction of 70%. Conclusion:The treatment of patients with severe hypercholesterolemia should aim at reducing the LDL-C level. We suggest that hemodialysis contributed to the significant reduction of LDL cholesterol level in our case; and therefore might be a potential tool for reducing high LDL-C levels in these patients.

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Role of ezetimibe in non-alcoholic fatty liver disease

Cited by 25 publications

References 23 publications

Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease

Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Severe hypercholesterolemia effectively lowered with hemodialysis: a case report

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