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The Role of Probiotics in Nonalcoholic Fatty Liver Disease: A New Insight into Therapeutic Strategies.
Meroni, M, Longo, M, Dongiovanni, P
Nutrients. 2019;(11)
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathological hepatic conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may predispose to liver cirrhosis and hepatocellular carcinoma (HCC). Due to the epidemic obesity, NAFLD is representing a global health issue and the leading cause of liver damage worldwide. The pathogenesis of NAFLD is closely related to insulin resistance (IR), adiposity and physical inactivity as well as genetic and epigenetic factors corroborate to the development and progression of hepatic steatosis and liver injury. Emerging evidence has outlined the implication of gut microbiota and gut-derived endotoxins as actively contributors to NAFLD pathophysiology probably due to the tight anatomo-functional crosstalk between the gut and the liver. Obesity, nutrition and environmental factors might alter intestinal permeability producing a favorable micro-environment for bacterial overgrowth, mucosal inflammation and translocation of both invasive pathogens and harmful byproducts, which, in turn, influence hepatic fat composition and exacerbated pro-inflammatory and fibrotic processes. To date, no therapeutic interventions are available for NAFLD prevention and management, except for modifications in lifestyle, diet and physical exercise even though they show discouraging results due to the poor compliance of patients. The premise of this review is to discuss the role of gut-liver axis in NAFLD and emphasize the beneficial effects of probiotics on gut microbiota composition as a novel attractive therapeutic strategy to introduce in clinical practice.
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2.
Determinants of ectopic liver fat in metabolic disease.
Bosy-Westphal, A, Braun, W, Albrecht, V, Müller, MJ
European journal of clinical nutrition. 2019;(2):209-214
Abstract
Common obesity-associated hepatic steatosis (nonalcoholic fatty liver disease (NAFLD)) and insulin resistance are mainly caused by dysfunctional adipose tissue. This adipose tissue dysfunction leads to increased delivery of NEFA and glycerol to the liver that (i) drives hepatic gluconeogenesis and (ii) facilitates the accumulation of lipids and insulin signaling inhibiting lipid intermediates. Dysfunctional adipose tissue can be caused by impaired lipid storage (overflow hypothesis, characterized by large visceral adipocytes) or increased lipolysis (due to impaired postprandial suppression of lipolysis in inflamed, insulin-resistant adipocytes). In line with the adipose tissue expandability hypothesis the amount and distribution of adipose tissue correlate with its dysfunction and thus with liver fat. This relationship is however modified by endocrine effects on lipid storage and lipolysis as well as dietary effects on hepatic lipogenesis and lipid oxidation. The association between body composition characteristics like visceral obesity or fat cell size and ectopic liver fat is modified by these influences. Phenotyping obesity according to metabolic risk should integrate body composition characteristics, endocrine parameters and information on diet.
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3.
A review of synbiotic efficacy in non-alcoholic fatty liver disease as a therapeutic approach.
Sangouni, AA, Ghavamzadeh, S
Diabetes & metabolic syndrome. 2019;(5):2917-2922
Abstract
According to recent epidemiological studies, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the worldwide. Pathophysiological pathways and mechanisms involved in NAFLD are not fully clear, but Inflammation, insulin resistance, oxidative stress, obesity and dyslipidemia are among the main causes of NAFLD. There is still no standard drug for the treatment of NAFLD. Diet modification, weight loss and physical activity are considered as the main treatment line for this disease. It has been shown that gut microbiota imbalance is associated with the main factors causing of NAFLD. Synbiotics, which have positive effects on the balance of gut microbiota, are a combination of prebiotics and probiotics. It is believed that the consumption of synbiotics can help to treatment of NAFLD through effect on gut microbiota and subsequently improving the risk factors of this disease. The purpose of this review is to investigate the effects of synbiotics on the main causes of NAFLD based on existing evidence, especially the clinical effects of synbiotics supplementation in patients with NAFLD.
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4.
Short-term Dietary Interventions for the Management of Nonalcoholic Fatty Liver.
Stokes, CS, Lammert, F, Krawczyk, M
Current medicinal chemistry. 2019;(19):3483-3496
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) affects millions of individuals on a global scale and currently no gold standard treatment exists. The risk of developing NAFLD is considerably higher with increasing body mass index. Consequently, weight loss should be recommended to all overweight patients with fatty liver. However, lifestyle interventions, irrespective of weight status, may also influence the condition. The aim herein is to present examples of short-term interventions which assess direct effects of dietary-related components on hepatic steatosis. METHODS This review includes studies with short-term dietary-related interventions of up to 16 weeks that evaluate their efficacy in reducing intrahepatic lipid contents (hepatic steatosis). This review primarily focuses on the three main macronutrients: dietary carbohydrates, fats and proteins. RESULTS High saturated fat intake and high consumption of carbohydrates, particularly from simple sugars such as fructose are reported as risk factors for hepatic steatosis. Overall, shortterm hypocaloric diets have shown beneficial effects in reducing intrahepatic lipid contents. Macronutrient manipulations such as carbohydrate restriction as well as the consumption of unsaturated fatty acids are also reported to have efficacious effects. CONCLUSION This review highlights the different dietary interventions that can influence hepatic steatosis in the short term, illustrating both pro and anti-steatotic effects.
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5.
Sarcopenia and fatty liver disease.
Kim, JA, Choi, KM
Hepatology international. 2019;(6):674-687
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease which may progress to non-alcoholic steatohepatitis. The prevalence of sarcopenia, which is the loss of muscle mass and strength, is increasing in the aging society. Recent studies reported the relationship between NAFLD and sarcopenia. The skeletal muscle is the primary organ for glucose disposal. Loss of muscle mass can cause insulin resistance, which is an important risk factor for NAFLD. Moreover, obesity, chronic low-grade inflammation, vitamin D deficiency, physical inactivity, hepatokines, and myokines might be involved in the pathophysiologic mechanism of sarcopenia and NAFLD. Although most of the previous studies have demonstrated the positive correlation between sarcopenia and NAFLD, the difference in diagnostic methods of sarcopenia and NAFLD leads to difficulties in interpretation and application. This review discusses the concept and diagnosis of sarcopenia and NAFLD, common pathophysiology, and clinical studies linking sarcopenia to NAFLD. The presentation of the association between sarcopenia and NAFLD may provide an opportunity to prevent the deterioration of fatty liver disease.
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6.
Lipid mediators of liver injury in nonalcoholic fatty liver disease.
Liangpunsakul, S, Chalasani, N
American journal of physiology. Gastrointestinal and liver physiology. 2019;(1):G75-G81
Abstract
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathological phenotypes ranging from simple steatosis to more severe liver disease associated with cell injury, including nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Only a subset of patients with NAFLD develop NASH from yet incompletely understood mechanisms. Emerging data suggest lipid species other than triglycerides as contributors to the pathogenesis of NASH. In this mini review, we focus on the recent data on the mechanisms of NASH, focusing on these lipid mediators and their potential as therapeutic targets in NASH.
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7.
The Potential Use of Metabolic Cofactors in Treatment of NAFLD.
Mardinoglu, A, Ural, D, Zeybel, M, Yuksel, HH, Uhlén, M, Borén, J
Nutrients. 2019;(7)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is caused by the imbalance between lipid deposition and lipid removal from the liver, and its global prevalence continues to increase dramatically. NAFLD encompasses a spectrum of pathological conditions including simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver cancer. Even though there is a multi-disciplinary effort for development of a treatment strategy for NAFLD, there is not an approved effective medication available. Single or combined metabolic cofactors can be supplemented to boost the metabolic processes altered in NAFLD. Here, we review the dosage and usage of metabolic cofactors including l-carnitine, Nicotinamide riboside (NR), l-serine, and N-acetyl-l-cysteine (NAC) in human clinical studies to improve the altered biological functions associated with different human diseases. We also discuss the potential use of these substances in treatment of NAFLD and other metabolic diseases including neurodegenerative and cardiovascular diseases of which pathogenesis is linked to mitochondrial dysfunction.
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8.
Are Lifestyle Therapies Effective for NAFLD Treatment?
El-Agroudy, NN, Kurzbach, A, Rodionov, RN, O'Sullivan, J, Roden, M, Birkenfeld, AL, Pesta, DH
Trends in endocrinology and metabolism: TEM. 2019;(10):701-709
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the most common liver disorder worldwide. Specifically, nonalcoholic steatohepatitis (NASH) and fibrosis pose an enormous burden for patients and health-care systems. In the absence of approved pharmacological therapies, effective lifestyle interventions for NAFLD, such as dietary strategies and exercise training, are currently the therapeutic strategies of choice. This review covers the influence of macronutrient quality and quantity (i.e., low-carbohydrate and high-protein diets), for successful reduction of intrahepatocellular lipids (IHL). Moreover, we discuss the effectiveness of different modalities of physical exercising with and without weight loss. These lifestyle modifications not only provide strategies to reduce IHL but may also hold a still underestimated potential to induce improvement and/or even remission of NAFLD.
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9.
[Pharmacological treatment of NASH].
Serfaty, L
Presse medicale (Paris, France : 1983). 2019;(12):1489-1495
Abstract
Lifestyle modifications, especially weight loss, are efficient on NASH liver injury, however rarely followed in clinical practice. The target population of pharmacologic treatments is represented by patients with NASH and fibrosis. Out of histological improvement, efficacy of treatments should be assessed through liver morbi-mortality benefit, but also on extrahepatic events, such as cardiovascular. Among anti-diabetic treatments, glitazones et GLP-1 agonists have shown efficacy on histological liver injury. Vitamin E is efficient on liver injury but at the cost of prostate cancer and stroke over risk. About 60 new molecules are under investigation in NASH and have 4 different types of mechanism of action: metabolic, oxidative stress/apoptosis, anti inflammatory and anti fibrotic. A phase 3 trial evaluating obeticholic acid have shown a 72 weeks duration treatment improved significantly fibrosis.
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10.
Current treatment options for nonalcoholic fatty liver disease.
Shetty, A, Syn, WK
Current opinion in gastroenterology. 2019;(3):168-176
Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the United States and is strongly associated to the metabolic syndrome. In this review, we will discuss the evidence behind the current recommendations on lifestyle modifications and available treatment options for NAFLD. RECENT FINDINGS The unrelenting rise in obesity and diabetes epidemic has led to a large healthcare burden from NAFLD and it is projected to continue to grow over the next two decades. Lifestyle modification that leads to weight loss is effective at treating NAFLD, but these modifications require a multidisciplinary approach for success in the real world. Multiple pharmacologic treatment options have been studied with promising results, but none have been approved for treatment in the United States. Clinical trials are on-going to study further pharmacologic treatment alternatives. SUMMARY NAFLD is the most common chronic liver disease in United States, and an independent risk factor for mortality. Implementation of lifestyle modifications through a multidisciplinary approach and careful selection of patients for pharmacologic interventions will be essential for successful management of NAFLD.