An Evidence-Based Review of Statin Use in Patients With Nonalcoholic Fatty Liver Disease

Sigler, Meredith; Congdon, Lee; Edwards, Krystal L.

doi:10.1177/1179552218787502

Cited by 49 publications

(46 citation statements)

References 61 publications

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“…Our findings that liver fat may be an important mediator of the effect of cholesterol-lowering on T2D is consistent with a report showing that liver fat may help identify statin-taking individuals at risk of T2D (42). Finally, it is noteworthy that the HMGCR variant that lowers LDL-C is not associated with any significant change in liver enzymes, potentially reflecting the lack of an increase in NAFLD incidence seen with statin medications (43).…”

Section: Discussionmentioning

confidence: 99%

Type-2 diabetes with low LDL-C: genetic insights into a unique phenotype

Klimentidis

Arora

Newell

et al. 2019

Preprint

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21Although hyperlipidemia is traditionally considered a risk factor for type-2 diabetes (T2D), 22 evidence has emerged from statin trials and candidate gene investigations suggesting that lower 23 LDL-C increases T2D risk. We thus sought to comprehensively examine the phenotypic and 24 genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that 25 LDL-C was negatively associated with T2D (OR=0.43[0.41, 0.45] per mmol/L unit of LDL-C), 26 despite positive associations of LDL-C with HbA1c and BMI. We then performed the first 27 genome-wide exploration of variants simultaneously associated with lower LDL-C and increased 28 T2D risk, using data on LDL-C from the UK Biobank (n=431,167) and the GLGC consortium 29 (n=188,577), and T2D from the DIAGRAM consortium (n=898,130). We identified 31 loci 30 associated with lower LDL-C and increased T2D, capturing several potential mechanisms. Seven 31 of these loci have previously been identified for this phenotype, and 9 have previously been 32 implicated in non-alcoholic fatty liver disease. Finally, two-sample Mendelian randomization 33 analyses suggest that low LDL-C causes T2D, although causal interpretations are challenging 34 due to pleiotropy. Our findings extend our current understanding of the higher T2D risk among 35 individuals with low LDL-C, and of the underlying mechanisms, including those underlying the 36 diabetogenic effect of LDL-C-lowering medications. 38Rates of cardiovascular disease (CVD) and type-2 diabetes (T2D) are among the most 39 pressing health concerns worldwide. These two diseases share many risk factors, and tend to co-40 occur; T2D carries a 2-4 fold increase in risk for CVD, and more than 70% of patients with T2D 41 will die from cardiovascular complications (1). Yet, there remains controversy over whether all 42 risk factors exert similar effects on the risk of these two conditions. Low-density lipoprotein 43 cholesterol (LDL-C) is a class of highly atherogenic particles, and circulating levels of LDL-C 44 are a causal risk factor for CVD across the lifespan (2). Lipid lowering medications, in particular 45 from the statin drug class, are effective at lowering levels of LDL-C which has a dose-response 46 relationship with a reduction in adverse cardiovascular events (3). The perception of a strong 47 inter-relationship of T2D with hyperlipidemia, in particular higher LDL-C, has led to a standard 48 of care in which lipid-lowering medications are a common therapeutic option for T2D. For 49 example, the American Diabetes Association (ADA) recommends high intensity statin use for 50 individuals with diabetes with prevalent atherosclerotic cardiovascular disease (ASCVD) or a 51 greater than 20% 10-year risk of ASCVD until they reach recommended stringent targets of 52 LDL-C < 70mg/dL. The ADA further recommends moderate-intensity statin use for T2D 53 patients 40 years and older without ASCVD (4). 54A recent analysis of national registry data from Scotland showed that 83.6% and 71.1% 55 of T2D patients with and...

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Section: Discussionmentioning

confidence: 99%

Type-2 diabetes with low LDL-C: genetic insights into a unique phenotype

Klimentidis

Arora

Newell

et al. 2019

Preprint

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“…Patients with NAFLD do not present a higher risk for serious liver injury caused by statins, so they can be used to treat dyslipidemia in patients with NAFLD [6]. A recent review that included 12 trials regarding statin therapy in patients with NAFLD has shown that no study reported elevated liver enzymes caused by statin treatment, with some of them showing improved transaminase levels [10]. Lowering cholesterol level in dyslipidemic patients with very high cardiovascular risk reduces the incidence of both cardiovascular morbidity and mortality.…”

Section: Resultsmentioning

confidence: 99%

Atorvastatin in the Treatment of Dyslipidemic Patients with Very High Cardiovascular Risk and Nonalcoholic Fatty Liver Disease

Costache¹,

Garleanu²,

Aursulesei³

et al. 2019

Rev. Chim.

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Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after ruling out other causes of hepatic steatosis. The aim of the study is to identify the role of statin therapy in dyslipidemic patients with very high cardiovascular risk and NAFLD in achieving low density lipoprotein (LDL) cholesterol targets while also evaluating the changes in liver enzymes levels. This prospective study included 140 patients with NAFLD, hyperlipidemia and elevated cardiovascular risk. Serum lipids were assessed and liver function tests were performed at baseline and at 6 months follow up in 10 mg/ 20 mg daily atorvastatin treatment schedule. The results showed that total cholesterol, LDL cholesterol and triglycerides were significantly reduced at 6 months follow-up, while high density lipoprotein (HDL) cholesterol has not undergone important changes. Statin treatment significantly improved alanine aminotransferase serum levels, whereas aspartate aminotransferase levels were not significantly reduced between baseline and follow-up. Although statin therapy appears to be safe and effective for use in patients with NAFLD, an insufficient treatment is commonly observed in clinical practice, in order to avoid liver damage . NAFLD is not only a major cause of liver related morbidity and mortality, but also an independent cardiovascular risk factor, with cardiovascular mortality being the most important cause of death. Therefore, detecting and modifying risk factors without impairing liver function is desirable.

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“…Additionally, metformin, statins, and fibrates, are currently being tested as NAFLD treatments in clinical trials. However, these drugs have significant adverse side effects, including enhanced risk of infection and osteoporosis (55)(56). Hence, novel treatment candidates with high efficacy and minimal side effects are urgently demanded for the treatment of NAFLD (57).…”

Section: Treatmentmentioning

confidence: 99%

Toward Nonalcoholic Fatty Liver Treatment; A Review on Herbal Medicine Treatment

2020

jcr

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This study, review the nonalcoholic fatty liver treatment with emphasis on herbal medicine treatment. The accumulation of the mass of triglycerides by 5% in the liver cells of those who are not alcoholic leads to a situation called nonalcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver is known as the most common liver disorder in the world, such that its prevalence varies from 3% to 25% in different populations of the world per race, age, sex, place of residence and lifestyle. Numerous studies have been carried out on the NAFLD and its pathological mechanism and are still ongoing. In classification of the causes of fatty liver, two general groups can be noted: (i) an effective group with indirect effects such as hypothyroidism, pituitary hypoplasia, polycystic ovarian syndrome, and sleep apnea; (ii) The other group is directly involved in the development of this disease in individuals such as abdominal obesity, metabolic syndrome and type 2 diabetes. Most patients are asymptomatic and are diagnosed by disturbed liver tests. This disease is the most common cause of liver enzymes disorder after hepatitis and chronic liver disease. In more than three-fourths of patients during a clinical examination, the increased size of liver is visible, and the most common symptom is excessive fatigue, lethargy, and pain in the upper right abdomen. The patients may complain of persistent itching, jaundice or complications caused by the increased portal pressure. If the disease leads to liver cirrhosis, hepatomegaly is seen in most cases. In most cases, the patient only finds out about the fatty liver when a regular blood test (generally liver function tests) shows a problem. "Alanine aminotransferase" and "Aspartate aminotransferase" are the most important liver enzymes, and their increase of 1.5-2 times in the tests shows the involvement of liver with this disease. Due to the key role of lipid accumulation in NAFLD progression, inhibition of lipid accumulation is a major focus of anti-NAFLD drug development. A variety of anti-NAFLD agents are currently in preclinical development. Additionally, metformin, statins, and fibrates, are currently being tested as NAFLD treatments in clinical trials. This study aims to review medicinal herbs used to treat NAFLD around the world. The obtained results of the present review investigation demonstrated that 27 medicinal herbs were found that traditionally used to treat NAFLD around the world. The most parts of these plants are leaves, root, and flowers, respectively; whereas these medicinal herbs are most commonly used in countries of Asian and African such as Iran, Pakistan, India and South Africa, etc. The results demonstrated that medicinal herbs have universally used to treat NAFLD. Thus, we can consider them as alternative agents for treatment of NAFLD; nevertheless, more investigations are mandatory to elucidate the precise mechanisms and also toxicity of these plants in human subjects.

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An Evidence-Based Review of Statin Use in Patients With Nonalcoholic Fatty Liver Disease

Cited by 49 publications

References 61 publications

Type-2 diabetes with low LDL-C: genetic insights into a unique phenotype

Type-2 diabetes with low LDL-C: genetic insights into a unique phenotype

Atorvastatin in the Treatment of Dyslipidemic Patients with Very High Cardiovascular Risk and Nonalcoholic Fatty Liver Disease

Toward Nonalcoholic Fatty Liver Treatment; A Review on Herbal Medicine Treatment

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