Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis

Lee, Hyoyoung; Jun, Dae Won; Kim, Hyun Jung; Oh, Hongseob; Saeed, Waqar Khalid; Ahn, Hyeong Sik; Cheung, Ramsey; Nguyen, Mindie H.

doi:10.3904/kjim.2017.194

Cited by 24 publications

(17 citation statements)

References 35 publications

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“…There is evidence that dietary cholesterol may also favor NASH development in humans [ 47 , 48 , 49 ] and the interruption of intestinal cholesterol absorption by ezetimibe has been shown to be beneficial in NAFLD patients in a meta-analysis of several clinical studies [ 16 ]. Notably, in one study ezetimibe reduced the NASH activity score without affecting steatosis [ 50 ]. A possible interaction between dietary cholesterol and fatty acid composition of the diet apparently was not systematically analyzed in human studies.…”

Section: Discussionmentioning

confidence: 99%

Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol

et al. 2018

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While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.

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Section: Discussionmentioning

confidence: 99%

Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol

et al. 2018

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“…However, the clinical trial by Loomba et al ( 59 ) with 50 patients showed that ezetimibe failed to significantly reduce liver fat in NAFLD as assessed by MRI-PDDF imaging. A recent meta-analysis, which exclusively included studies assessing NAFLD/NASH based on biopsy, with only one study that was based MRI-PDFF imaging, showed that ezetimibe decreased NAFLD activity score (NAS) but not hepatic steatosis ( 60 ). It was noted that current available data about ezetimibe and NAFLD/NASH were generated from limited number of clinical trials with small sample size ( 69 ).…”

Section: Cholesterol Lowering Drugs In the Management Of Nafld/nashmentioning

confidence: 99%

Disturbances in Cholesterol Homeostasis and Non-alcoholic Fatty Liver Diseases

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) is a major health problem associated with obesity and other features of the metabolic syndrome including insulin resistance and dyslipidemia. The accumulation of lipids in hepatocytes causes liver damage and triggers inflammation, fibrosis, and cirrhosis. Beside fatty acids and triglycerides, evidence showed an increased accumulation of free cholesterol in the liver with subsequent toxic effects contributing to liver damage. The maintenance of cholesterol homeostasis in the body requires a balance between several pathways responsible for cholesterol synthesis, transport and conversion into bile acids. Intestinal absorption is also one of the major determinants of cholesterol homeostasis. The nature of changes in cholesterol homeostasis associated with NAFLD has been a subject of extensive investigations. In this article, we will attempt to provide a brief overview of the current knowledge about the disturbances in cholesterol metabolism associated with NAFLD and discuss how certain molecular targets of these pathways could be exploited for the treatment of this multifactorial disease.

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“…According to a consensus panel in the United Kingdom, the addition of ezetimibe to statins reduces LDL by an additional 20% compared to statins alone [ 86 ]. In a meta-analysis of 5 trials involving a total of 199 NAFLD patients, NAFLD activity score was decreased; however, steatosis was not alleviated with ezetimibe [ 87 ]. In the landmark IMPROVE-IT trial, which included 18,000 patients with acute coronary syndrome, ezetimibe was associated with an improvement in cardiovascular profile when it was added to statins [ 88 ].…”

Section: Potential Therapies Targeting Nafld and Afmentioning

confidence: 99%

Nonalcoholic fatty liver disease and atrial fibrillation: possible pathophysiological links and therapeutic interventions

Haghbin

Gangwani

Ravi

et al. 2020

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Atrial fibrillation (AF) and nonalcoholic fatty liver disease (NAFLD) share common risk factors and appear to have an association. Independently, the incidence and prevalence of both diseases are on the rise. Epidemiological evidence, experimental studies and various randomized clinical trials suggest a link between the 2 entities, delineating cumulative risks and clinical strategies to improve outcomes. Dyslipidemia, insulin resistance, inflammatory milieu, and activation of the renin-angiotensin system are likely common pathophysiological mechanisms linking AF and NAFLD. In this article we review the known pathways and pathophysiology that link the 2 conditions. This review also discusses therapies that target both NAFLD and AF, such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, metformin, and vitamin E. We further discuss other potential medications that have shown effects in NAFLD or AF through anti-inflammatory, antidiabetic, lipid-lowering, or renin-angiotensin system inhibiting effects. Future epidemiological studies are needed to establish a direct causal relationship between NAFLD and AF.

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Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis

Cited by 24 publications

References 35 publications

Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol

Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol

Disturbances in Cholesterol Homeostasis and Non-alcoholic Fatty Liver Diseases

Nonalcoholic fatty liver disease and atrial fibrillation: possible pathophysiological links and therapeutic interventions

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