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1.
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.
A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.
Chashmniam, S, Mirhafez, SR, Dehabeh, M, Hariri, M, Azimi Nezhad, M, Nobakht M Gh, BF
European journal of clinical nutrition. 2019;(9):1224-1235
Abstract
BACKGROUND/OBJECTIVES Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. SUBJECTS/METHODS Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR. RESULTS Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC). CONCLUSIONS Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.
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3.
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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4.
Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease.
Inoue, M, Hayashi, A, Taguchi, T, Arai, R, Sasaki, S, Takano, K, Inoue, Y, Shichiri, M
Journal of diabetes investigation. 2019;(4):1004-1011
Abstract
AIMS/INTRODUCTION Non-alcoholic fatty liver disease is frequently associated with type 2 diabetes, and constitutes an important risk factor for the development of hepatic fibrosis and hepatocellular carcinoma. Because there remains no effective drug therapy for non-alcoholic fatty liver disease associated with type 2 diabetes, we evaluated the efficacy of sodium-glucose cotransporter 2 inhibitor. METHODS AND MATERIALS In the present pilot, prospective, non-randomized, open-label, single-arm study, we evaluated the effect of 100 mg canagliflozin administered once daily for 12 months on serological markers, body composition measured by bioelectrical impedance analysis method and hepatic fat fraction measured by magnetic resonance imaging in type 2 diabetes patients with non-alcoholic fatty liver disease. RESULTS Canagliflozin significantly reduced body and fat mass, and induced a slight decrease in lean body or muscle mass that did not reach significance at 6 and 12 months. Reductions in fat mass in each body segment (trunk, arms and legs) were evident, whereas those in lean body mass were not. The hepatic fat fraction was reduced from a baseline of 17.6 ± 7.5% to 12.0 ± 4.6% after 6 months and 12.1 ± 6.1% after 12 months (P < 0.0005 and P < 0.005), whereas serum liver enzymes and type IV collagen concentrations improved. From a mean baseline hemoglobin A1c of 8.7 ± 1.4%, canagliflozin significantly reduced hemoglobin A1c after 6 and 12 months to 7.3 ± 0.6% and 7.7 ± 0.7% (P < 0.0005 and P < 0.01). CONCLUSIONS Canagliflozin reduced body mass, fat mass and hepatic fat content without significantly reducing muscle mass.
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5.
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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6.
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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7.
N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL.
Oliveira, CP, Cotrim, HP, Stefano, JT, Siqueira, ACG, Salgado, ALA, Parise, ER
Arquivos de gastroenterologia. 2019;(2):184-190
Abstract
BACKGROUND Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.
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8.
Evaluation of the Effect Derived from Silybin with Vitamin D and Vitamin E Administration on Clinical, Metabolic, Endothelial Dysfunction, Oxidative Stress Parameters, and Serological Worsening Markers in Nonalcoholic Fatty Liver Disease Patients.
Federico, A, Dallio, M, Masarone, M, Gravina, AG, Di Sarno, R, Tuccillo, C, Cossiga, V, Lama, S, Stiuso, P, Morisco, F, et al
Oxidative medicine and cellular longevity. 2019;:8742075
Abstract
Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α, transforming growth factor β, interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline (p < 0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients (p < 0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome (p < 0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.
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9.
Nigella sativa and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: Results from a randomized, double-blind, placebo-controlled, clinical trial.
Darand, M, Darabi, Z, Yari, Z, Saadati, S, Hedayati, M, Khoncheh, A, Hosseini-Ahangar, B, Alavian, SM, Hekmatdoost, A
Complementary therapies in medicine. 2019;:204-209
Abstract
OBJECTIVE The aim of this study was to assess the effects of Nigella sativa consumption on inflammatory biomarkers in patients with Non-alcoholic fatty liver disease (NAFLD). METHODS This is a randomized, double-blind, placebo-controlled clinical trial. Fifty NAFLD patients were assigned to receive either two gram/day Nigella sativa seed as Nigella sativa group (NSG), or two gram/day starch as placebo group (PG) for 12 weeks. RESULTS At the end of the study, the serum levels of tumor necrosis factor-α (TNF-α) decreased significantly compared with the beginning of the study in both groups, while the levels of high sensitive C reactive protein (hs-CRP) and nuclear factor kappa-B (NF-κB) only decreased significantly in the NSG (P 0 < 0.05). Only reduction in the serum levels of TNF-α was significantly more in NSG compared to the PG (P = 0.001). After adjusting the effects of confounding factors, the results remained unchanged. According to Fibroscan exam, hepatic steatosis and its percentage decreased significantly only in the NSG (P 0 < 0.005); however, the changes were not significantly different between two groups. After adjusting for confounding factors, only steatosis percentage reduction was significantly more in the NSG compared to PG (P = 0.005). CONCLUSION Our results have shown that two gram/day consumption of Nigella sativa can reduce inflammatory biomarkers in patients with NAFLD. Further studies with different doses are highly recommended to find the optimal dosage.
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10.
Hyperferritinemia in Nonalcoholic Fatty Liver Disease: Iron Accumulation or Inflammation?
Moris, W, Verhaegh, P, Jonkers, D, Deursen, CV, Koek, G
Seminars in liver disease. 2019;(4):476-482
Abstract
Hyperferritinemia, observed in inflammation, iron overload as well as in combination of both, is found in ∼30% of nonalcoholic fatty liver disease (NAFLD) patients. The authors summarized the evidence regarding the potential cause of hyperferritinemia in NAFLD, as this may affect the indicated therapy. A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, and the Cochrane library. In the majority of NAFLD patients, hyperferritinemia is due to inflammation without hepatic iron overload. In a smaller group, a dysmetabolic iron overload syndrome (DIOS) is found, showing hyperferritinemia in combination with mild iron accumulation in the reticuloendothelial cells. The smallest group consists of NAFLD patients with hemochromatosis. Phlebotomy is only effective with hepatocellular iron overload and should not be the treatment when hyperferritinemia is related to inflammation, whether or not combined with DIOS. Treatment with lifestyle changes is to date probably the more effective way until new medication is becoming available.