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Dyslipidemia in patients with nonalcoholic fatty liver disease.

ABSTRACT: Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction of the very low-density lipoprotein particles and dysregulated clearance of lipoproteins from the circulation. There is unequivocal evidence that cardiovascular disease is the most common cause of mortality in patients with NAFLD. Aggressive treatment of dyslipidemia plays a critical role in the overall management of patients with NAFLD. Statins are the first-line agents to treat high cholesterol and their dosage should be adjusted based on achieving therapeutic targets and tolerability. Although all statins appear to be effective in improving cholesterol levels in patients with NAFLD, there is more experience with atorvastatin in patients with NAFLD; furthermore, it is the only statin to date to show a reduced cardiovascular morbidity in patients with NAFLD. The risk for serious liver injury from statins is quite rare and patients with NAFLD are not at increased risk for statin hepatotoxicity. Omega-3 fatty acids are perhaps the first choice to treat hypertriglyceridemia because of their safety, tolerability, and efficacy in improving serum triglycerides, as well as their potential to improve liver disease.

SUBMITTER: Chatrath H

PROVIDER: S-EPMC3654545 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Dyslipidemia in patients with nonalcoholic fatty liver disease.

Chatrath Hemant H Vuppalanchi Raj R Chalasani Naga N

Seminars in liver disease 20120201 1

Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction ...[more]

PMID: 22418885

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Project description:Statins, the intestinal cholesterol transporter inhibitor (ezetimibe), and PCSK9 inhibitors can reduce serum LDL-C levels, leading to a significant reduction in cardiovascular events. However, these events cannot be fully prevented even when maintaining very low LDL-C levels. Hypertriglyceridemia and reduced HDL-C are known as residual risk factors for ASCVD. Hypertriglyceridemia and/or low HDL-C can be treated with fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids. Fibrates were demonstrated to be PPARα agonists and can markedly lower serum TG levels, yet were reported to cause some adverse effects, including an increase in the liver enzyme and creatinine levels. Recent megatrials of fibrates have shown negative findings on the prevention of ASCVD, which were supposed to be due to their low selectivity and potency for binding to PPAR α. To overcome the off-target effects of fibrates, the concept of a selective PPARα modulator (SPPARMα) was proposed. Kowa Company, Ltd. (Tokyo, Japan), has developed pemafibrate (K-877). Compared with fenofibrate, pemafibrate showed more favorable effects on the reduction of TG and an increase in HDL-C. Fibrates worsened liver and kidney function test values, although pemafibrate showed a favorable effect on liver function test values and little effect on serum creatinine levels and eGFR. Minimal drug-drug interactions of pemafibrate with statins were observed. While most of the fibrates are mainly excreted from the kidney, pemafibrate is metabolized in the liver and excreted into the bile. It can be used safely even in patients with CKD, without a significant increase in blood concentration. In the megatrial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels, the incidence of cardiovascular events did not decrease among those receiving pemafibrate compared to those receiving the placebo; however, the incidence of nonalcoholic fatty liver disease was lower. Pemafibrate may be superior to conventional fibrates and applicable to CKD patients. This current review summarizes the recent findings on pemafibrate.

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Dyslipidemia in patients with nonalcoholic fatty liver disease.

Publications

Dyslipidemia in patients with nonalcoholic fatty liver disease.

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