Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT). A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. Daily Consumption of Synbiotic Yogurt Decreases Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. The Effect of Symbiotic Supplementation on Liver Enzymes, C-reactive Protein and Ultrasound Findings in Patients with Non-alcoholic Fatty Liver Disease: A Clinical Trial Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. Combined effects of synbiotic and sitagliptin versus sitagliptin alone in patients with nonalcoholic fatty liver disease Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind Randomized Clinical Trial Ginger Supplementation in Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Pilot Study Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non‐alcoholic steatohepatitis Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis Effect of Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease Utility of the ELF Test for Detecting Steatohepatitis in Morbid Obese Patients with Suspicion of Nonalcoholic Fatty Liver Disease Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial Nonalcoholic fatty liver disease and the renin-angiotensin system blockers in the patients with chronic kidney disease Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions.
Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease ( NAFLD ) to shift into one of the most frequent causes of chronic liver illness in childhood . Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used ; overall it ranges between 3 % and 10 % of pediatric population , increasing up to 70 % in patients with metabolic comorbidities ( Manco M , Bottazzo G , DeVito R et al , J Am Coll Nutr 27:667 - 676 , 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions , including type 2 diabetes ( T2D ) , obesity , and nonalcoholic steatohepatitis ( NASH ) . One of the emerging areas of the study is the link between liver diseases and gut microbiome , which has added new information to the underst and ing of the so-called gut-liver axis . In order to address the role of gut microbiome in NAFLD onset and progression , it is necessary to " decipher " operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and , hence , to address the function of the intestinal microbiome within the gut microbiota-liver axis . Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of  obesity and NAFLD in adults and children . Several r and omized clinical trials ( RCTs ) have been already published on  fecal microbiota transplantation  ( FMT ) , T2D , NASH , and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions , probiotics , symbiotics , and FMT BACKGROUND Probiotics have a beneficial effect on nonalcoholic fatty liver disease ( NAFLD ) in animal models . R and omized placebo-controlled trials ( RCTs ) in NAFLD are still lacking in humans despite a large number of data from animal research . AIM We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD . METHODS A total of 58 patients met the criteria for inclusion . They were r and omly assigned to receive the multi-probiotic " Symbiter " ( concentrated biomass of 14 probiotic bacteria genera Bifidobacterium , Lactobacillus , Lactococcus , Propionibacterium ) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment . The primary main outcomes were the changes in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in aminotransferase activity , serum lipids and cytokines ( TNF-α , IL-1β , IL-6 , IL-8 , and IFN-γ ) levels . Analysis of covariance was used to assess the difference between groups . RESULTS In the probiotic group , FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 ( p<0.001 ) but it did not change in the placebo group ( 82.57+/-2.45 to 81.6 + /-2.36 ; p=0.367 ) . In both groups a slight but not significant reduction of LS measured by SWE was detected . Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT . Among the markers of chronic systemic inflammatory state , only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic . CONCLUSION The probiotic " Symbiter "  reduces liver fat , aminotransferase activity , and the TNF-α and IL-6 levels in NAFLD patients . Modulation of the gut microbiota might represent a new therapy for NAFLD , which should be tested in larger studies Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in developed and developing countries . The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD . Objective We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers , adipokine concentration , and gut peptide concentration as secondary outcomes in patients with NAFLD . Methods In this 24-wk , open-label , r and omized controlled clinical trial , 102 patients [ 50 men and 52 women ; mean age : 40 y ; body mass index ( in kg/m2 ) ( mean ± SD ) : 31.2 ± 4.9 ] were r and omly assigned to 3 groups , including 2 intervention groups and 1 control group . The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle ( i.e. , diet and exercise ) . The control group was advised to follow a healthy lifestyle alone . We evaluated differences between groups in liver function measures by using repeated- measures ANOVA , ANCOVA , and logistic regression . Results At the end of the study , the grade s of NAFLD , as determined by ultrasonography , showed a significant decrease in the synbiotic group compared with the conventional and control groups ( P < 0.001 ) . The following significant mean ± SD decreases were seen in the synbiotic , conventional , and control groups , respectively : serum concentration of alanine aminotransferase ( -14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L ; P = 0.008 ) , aspartate aminotransferase ( -7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L ; P < 0.001 ) , alkaline phosphatase ( -26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L ; P = 0.024 ) , and γ-glutamyltransferase ( -6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L ; P < 0.001 ) . Conclusion Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD . This trial was registered at the Iranian Registry of Clinical Trials website ( www.i rct .ir ) as I RCT 2017020932417N2 BACKGROUND Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of synbiotic has been proposed as an effective treatment of NAFLD because of its modulating effect on the gut flora , which can influence the gut-liver axis . OBJECTIVE The objective was to evaluate the effects of supplementation with synbiotic on hepatic fibrosis , liver enzymes , and inflammatory markers in patients with NAFLD . DESIGN In a r and omized , double-blind , placebo-controlled clinical trial conducted as a pilot study , 52 patients with NAFLD were supplemented twice daily for 28 wk with either a synbiotic or a placebo capsule . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . RESULTS At the end of the study , the alanine aminotransferase ( ALT ) concentration decreased in both groups ; this reduction was significantly greater in the synbiotic group . At the end of the study , the following significant differences [ means ( 95 % CIs ) ] were seen between the synbiotic and placebo groups , respectively : ALT [ -25.1 ( -26.2 , -24 ) compared with -7.29 ( -9.5 , -5.1 ) IU/L ; P < 0.001 ] , aspartate aminotransferase [ -31.33 ( -32.1 , -30.5 ) compared with -7.94 ( -11.1 , -4.8 ) IU/L ; P < 0.001 ] , γ-glutamyltransferase [ -15.08 ( -15.5 , -14.7 ) compared with -5.21 ( -6.6 , -3.9 ) IU/L ; P < 0.001 ] , high-sensitivity C-reactive protein [ -2.3 ( -3 , -1.5 ) compared with -1.04 ( -1.5 , -0.6 ) mmol/L ; P < 0.05 ] , tumor necrosis factor-α [ -1.4 ( -1.7 , -1.1 ) compared with -0.59 ( -0.8 , -0.3 ) mmol/L ; P < 0.001 ] , total nuclear factor κ-B p65 [ -0.016 ( -0.022 , -0.011 ) compared with 0.001 ( -0.004 , -0.007 ) mmol/L ; P < 0.001 ] , and fibrosis score as determined by transient elastography [ - 2.98 ( -3.6 , -2.37 ) compared with -0.77 ( -1.32 , -0.22 ) kPa ; P < 0.001 ] . CONCLUSIONS Synbiotic supplementation in addition to lifestyle modification is superior to lifestyle modification alone for the treatment of NAFLD , at least partially through attenuation of inflammatory markers in the body . Whether these effects will be sustained with longer treatment duration s remains to be determined Background : Regarding to the growing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , concentrating on various strategies to its prevention and management seems necessary . The aim of this study was to determine the effects of symbiotic on C-reactive protein ( CRP ) , liver enzymes , and ultrasound findings in patients with NAFLD . Methods : Eighty NAFLD patients were enrolled in this r and omized , double-blind , placebo-controlled clinical trial . Participants received symbiotic in form of a 500 mg capsule ( containing seven species of probiotic bacteria and fructooligosaccharides ) or a placebo capsule daily for 8 weeks . Ultrasound grading , CRP , and liver enzymes were evaluated at the baseline and the end of the study . Results : In the symbiotic group , ultrasound grade decreased significantly compared to baseline ( P < 0.005 ) but symbiotic supplementation was not associated with changes in alanine aminotransferase ( ALT ) and aspartate transaminase ( AST ) levels . In the placebo group , there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased ( P = 0.002 , P = 0.02 , respectively ) . CRP values remained static in either group . Conclusions : Symbiotic supplementation improved steatosis  in NAFLD patients and might be useful in the management of NAFLD or protective against its progression Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease ( NAFLD ) . But it remains unknown in nonobese NAFLD . This prospect i ve , cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression . A total of 126 nonobese subjects were enrolled : 43 NAFLD and 83 healthy controls ( HC ) . The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region . Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD . Compared with HC , patients had 20 % more phylum Bacteroidetes ( p = 0.005 ) and 24 % less Firmicutes ( p = 0.002 ) . Within Firmicutes , four families and their 8 genera , which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria , were significantly decreased . Moreover , Gram-negative ( G− ) bacteria were prevalent in NAFLD ( p = 0.008 ) . Furthermore , a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD . This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression BACKGROUND The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease ( NAFLD ) . Hence , we performed a double-blind single center r and omized placebo-controlled trial ( RCT ) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD . METHODS A total of 48 patients met the criteria for inclusion . They were r and omly assigned to receive " Symbiter Omega " combination of probiotic biomass supplemented with flax and wheat germ oil ( 250 mg of each , concentration of omega-3 fatty acids 1 - 5 % ) or placebo for 8-weeks . The primary main outcomes were the change in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in transaminases level , serum lipids and cytokines levels . RESULTS In probiotic-omega group , FLI significantly decreased from 83.53±2.60 to 76.26±2.96 ( P<0.001 ) while no significant changes were observed in the placebo group ( 82.86±2.45 to 81.09±2.84 ; P=0.156 ) . Changes of LS in both groups were insignificant . Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase , triglycerides , and total cholesterol . Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group : IL-1β ( P=0.029 ) , TNF-α ( P<0.001 ) , IL-8 ( P=0.029 ) , IL-6 ( P=0.003 ) , and INF-γ ( P=0.016 ) . CONCLUSIONS Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat , improve serum lipids , metabolic profile , and reduce chronic systemic inflammatory state Background / Aims Non-alcoholic fatty liver disease ( NAFLD ) is one of the most prevalent chronic liver diseases in recent years . The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD . Methods In total , 138 NAFLD patients aged 18 - 60 years were enrolled in the study . Patients were r and omized to one of the following treatments for 16 weeks : Group I ( n=68 ) , sitagliptin 50 mg daily plus placebo ( one capsule per day ) or group II ( n=70 ) sitagliptin 50 mg daily plus synbiotic ( one capsule per day ) . Changes in fasting blood glucose ( FBS ) , liver enzymes , lipid profile , and body mass index were compared between the groups . Results The mean change in FBS  with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL , and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups ( P<0.001 ) . The mean change in cholesterol ( Chol ) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic . There was a significant difference between the two groups ( P=0.029 ) . The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein ( LDL ) , whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL . A significant difference was observed between the two groups ( P<0.001 ) . On the other h and , in the sitagliptin-synbiotic group , there was significant improvement in aspartate aminotransferase ( AST ) level  compared to the sitagliptin-placebo group ( P=0.018 ) . Conclusions Sitagliptin-synbiotic produced greater improvement in FBS , AST , Chol , and LDL compared to sitagliptin alone in patients with NAFLD The intestinal microbiota is closely associated with the development of obesity and nonalcoholic fatty liver disease ( NAFLD ) . This study investigated the effects of probiotic treatment on visceral fat area ( VFA ) and intrahepatic fat ( IHF ) fraction in NAFLD . Sixty-eight obese NAFLD patients ( > 5 % proton density fat fraction [ PDFF ] on magnetic resonance imaging [ MRI ] ) were r and omized to probiotic and placebo groups for 12 weeks . The probiotic mixture included 6 bacterial species . VFA and IHF were measured using the MRI-PDFF technique . Body weight and total body fat were reduced in the probiotic group but not in the placebo group . The mean IHF fraction was reduced after 12 weeks of treatment in the probiotic group compared to that at baseline ( from 16.3 ± 15.0 % to 14.1 ± 7.7 % , p = 0.032 ) but was not reduced in the placebo group . The decrease in IHF ( mean difference : −2.61 % , p = 0.012 ) was also greater in the probiotic group than in the placebo group . Reduction of triglyceride was greater in the probiotic treatment group than in the placebo group ( mean difference : −34.0 mg/dl , p = 0.0033 ) . However , the changes in IHF percentage and triglyceride levels were not different between placebo and control groups after adjusting for changes in body weight . Treatment with probiotics for 12 weeks result ed in significant reduction in IHF and body weight in obese NAFLD patients Objective : Nonalcoholic fatty liver disease ( NAFLD ) is a condition defined by exceeding triglycerides accumulation in the liver . The condition can develop into fibrosis , cirrhosis , and hepatocellular carcinoma . Considering the ever-increasing prevalence of NAFLD , the aim of the present study was to investigate the effects of probiotic supplementation on glycemic and inflammatory indices in patients with NAFLD . Methods : This r and omized clinical trial was conducted on 42 patients with NAFLD who had been referred to a gastroenterology clinic . Subjects in the intervention and control groups consumed 2 capsules/day probiotic or placebo , respectively , for 8 weeks . Fasting blood sugar ( FBS ) , insulin , insulin resistance , tumor necrosis factor alpha ( TNF-α ) , and interleukin 6 ( IL-6 ) were measured at baseline and at the end of the study . Results : Means of FBS , insulin , insulin resistance , and IL-6 were significantly different between groups after intervention ( p < 0.05 ) , whereas TNF-α was not significantly modified ( p > 0.05 ) . In the probiotic group , insulin , insulin resistance , TNF-α , and IL-6 decreased significantly at the end of the study compared to the beginning of study . Conclusion : Considering the effects of probiotic supplementation on the reduction of glycemic and inflammatory indices in patients with NAFLD , consumption of probiotics is recommended as a complementary therapy in these patients Background : Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common chronic liver diseases worldwide . The pathogenesis of this disease is closely associated with obesity and insulin resistance . Ginger can have hypolipidemic and antioxidant effects , and act as an insulinsensitizer . Objectives : The aim of this study was to evaluate the effects of ginger supplementation in NAFLD management . Patients and Methods : In a r and omized , double-blind , placebo-controlled clinical trial , 44 patients with NAFLD were assigned to take either two grams per day of a ginger supplement or the identical placebo , for 12 weeks . In both groups , patients were advised to follow a modified diet and physical activity program . The metabolic parameters and indicators of liver damage were measured at study baseline and after the 12 week intervention . Results : Ginger supplementation result ed in a significant reduction in alanine aminotransferase , γ-glutamyl transferase , inflammatory cytokines , as well as the insulin resistance index and hepatic steatosis grade in comparison to the placebo . We did not find any significant effect of taking ginger supplements on hepatic fibrosis and aspartate aminotransferase . Conclusions : Twelve weeks of two grams of ginger supplementation showed beneficial effects on some NAFLD characteristics . Further studies are recommended to assess the long-term supplementation effects Although non-alcoholic fatty liver disease ( NAFLD ) is the leading aetiology of liver disorders in the world , there is no proven treatment for NAFLD patients with normal or low BMI . The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI . In this r and omised , double-blind , placebo-controlled , clinical trial , fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks . Both groups were advised to follow a healthy lifestyle . At the end of the study , hepatic steatosis and fibrosis reduced in both groups ; however , the mean reduction was significantly greater in the synbiotic group rather than in the placebo group ( P<0·001 ) . Furthermore , serum levels of fasting blood sugar , TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group ( P<0·05 ) . Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI , at least partially through reduction in inflammatory indices . Further studies are needed to address the exact mechanism of action of these effects Gut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease ( NAFLD ) but r and omised controlled trials ( RCT ) are lacking in children Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries ; it can progress to nonalcoholic steatohepatitis ( NASH ) , cirrhosis and hepatocarcinoma . The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients . In a r and omized , controlled clinical trial , involving 50 biopsy-proven NASH patients , we investigated the effects of synbiotic supplementation on metabolic parameters , hepatic steatosis , intestinal permeability , small intestinal bacterial overgrowth ( SIBO ) and lipopolysaccharide ( LPS ) serum levels . Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone . Before and after the intervention we assessed steatosis by magnetic resonance imaging , intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing .  NASH patients presented high gut permeability , but low prevalence of SIBO . After the intervention , only the synbiotic group presented a reduction in steatosis , lost weight , diminished BMI and waist circumference measurement . Synbiotic did not improve intestinal permeability or LPS levels . We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss Non-alcoholic fatty liver disease ( NAFLD ) is the most common liver disease worldwide , characterized by liver fatty acid accumulation and fibrosis , not due to excessive alcohol consumption . Notably , nutritional habits have been reported to be implicated in the onset and severity of the hepatic damage , while the Mediterranean diet has shown beneficial effects on NAFLD . Free radicals and oxidative stress were suggested to be involved in the pathogenesis and progression of NAFLD , and several data highlighted the efficacy of antioxidant supplementation in its treatment . The aim of this study was to compare the effects of the Mediterranean diet , with or without an antioxidant complex supplement , in overweight patients suffering from NAFLD . In this prospect i ve study , fifty Caucasian overweight patients were r and omized into three groups ( Groups A – C ) . A personalized moderately hypocaloric Mediterranean diet was prescribed to all patients included in the A and B groups . In addition to the diet , Group B was administered antioxidant supplementation daily and for the period of six months . Group C did not have any type of treatment . The study proved that the Mediterranean diet alone or in association with the antioxidant complex  improved anthropometric parameters , lipid profile and reduced hepatic fat accumulation and liver stiffness . However , Group B patients , in which the diet was associated with antioxidant intake , showed not only a significant improvement in insulin sensitivity , but also a more consistent reduction of anthropometric parameters when compared with Group A patients . Taken together , these results support the benefit of antioxidant supplementation in overweight patients with NAFLD Background Hyperlipidemia , insulin resistance , and oxidative stress can heavily contribute to the initiation and progression of nonalcoholic fatty liver disease ( NAFLD ) . Currently , there is no established treatment for this disease . Recently , several studies have shown that ezetimibe ( EZ ) , a lipid-lowering drug , attenuates liver steatosis in an experimental NAFLD model . This study was design ed to assess the efficacy of long-term EZ monotherapy in patients with NAFLD . Methods A total of 45 patients with newly diagnosed liver biopsy-proven NAFLD were treated with EZ ( 10 mg/day ) for 24 months . NAFLD-related biochemical parameters , imaging by computerized tomography , and liver biopsy were studied before and after treatment . Results Ezetimibe therapy significantly improved NAFLD-related metabolic parameters including visceral fat area , fasting insulin , homeostasis model assessment of insulin resistance ( HOMA-R ) , triglycerides , total cholesterol , low-density lipoprotein cholesterol ( LDL-Ch ) , oxidative-LDL , the net electronegative charge modified-LDL , profiles of lipoprotein particle size and fatty acids component , and estimated desaturase activity .  EZ therapy also significantly lowered serum alanine aminotransferase and high-sensitivity C-reactive protein levels , whereas no significant changes were found in serum type IV collagen 7S , adiponectin , leptin , and resistin levels . Histological features of steatosis grade ( P = 0.0003 ) , necroinflammatory grade ( P = 0.0456 ) , ballooning score ( P = 0.0253 ) , and NAFLD activity score ( NAS ) ( P = 0.0007 ) were significantly improved from baseline . However , the fibrosis stage was not significantly ( P = 0.6547 ) changed . Conclusion The results in this study suggest that the long-term EZ therapy can lead to improvement in metabolic , biochemical , and histological abnormalities of NAFLD . Therefore , EZ may be a promising agent for treatment of NAFLD Background Morbid obese patients have a high rate of nonalcoholic fatty liver disease ( NAFLD ) and nonalcoholic steatohepatitis ( NASH ) . NASH is related to the progression and poor evolution of chronic hepatopathy in NAFLD , so that its detection makes it possible to identify the subjects who are most at risk in order to prioritize treatment . The ELF test ( Enhanced Liver Fibrosis test ; Siemens Diagnostics , NY , USA ) has been assessed for its capacity to detect fibrosis in patients with NAFLD , but its capacity for diagnosing NASH has not been checked . Aims Our objective is to determine the utility of the ELF test for detecting NASH in morbid obese patients with suspected NAFLD . Methods ELF values were determined in a cohort of obese patients who underwent bariatric surgery with suspected NAFLD .  Liver biopsy was used as the reference st and ard . Results The values of ELF were significantly higher in patients with NASH ( p = 0.002 ) and in those who presented with metabolic syndrome ( p = 0.047 ) . An ELF cut-off point of 8.72 allows the detection of patients with NASH with a sensitivity of 71.4 % and a specificity of 74.1 % ( AUC = 0.742 , p = 0.002 ) . Conclusions The ELF test is efficient for the identification of obese patients with NAFLD and early signs of steatohepatitis and fibrosis BACKGROUND & AIMS Prevalence of nonalcoholic fatty liver disease ( NAFLD ) has not been well established . The purpose of this study was to prospect ively define the prevalence of both NAFLD and nonalcoholic steatohepatitis ( NASH ) . METHODS Out patients 18 to 70 years old were recruited from Brooke Army Medical Center . All patients completed a baseline question naire and ultrasound . If fatty liver was identified , then laboratory data and a liver biopsy were obtained . RESULTS Four hundred patients were enrolled . Three hundred and twenty-eight patients completed the question naire and ultrasound .  Mean age ( range , 28 - 70 years ) was 54.6 years ( 7.35 ) ; 62.5 % Caucasian , 22 % Hispanic , and 11.3 % African American ; 50.9 % female ; mean body mass index ( BMI ) ( calculated as kg/m(2 ) ) was 29.8 ( 5.64 ) ; and diabetes and hypertension prevalence 16.5 % and 49.7 % , respectively . Prevalence of NAFLD was 46 % . NASH was confirmed in 40 patients ( 12.2 % of total cohort , 29.9 % of ultrasound positive patients ) . Hispanics had the highest prevalence of NAFLD ( 58.3 % ) , then Caucasians ( 44.4 % ) and African Americans ( 35.1 % ) . NAFLD patients were more likely to be male ( 58.9 % ) , older ( P = .004 ) , hypertensive ( P < .00005 ) , and diabetic ( P < .00005 ) . They had a higher BMI ( P < .0005 ) , ate fast food more often ( P = .049 ) , and exercised less ( P = 0.02 ) than their non-NAFLD counterparts . Hispanics had a higher prevalence of NASH compared with Caucasians ( 19.4 % vs 9.8 % ; P = .03 ) . Alanine aminotransferase , aspartate aminotransferase , BMI , insulin , Quantitative Insulin-Sensitivity Check Index , and cytokeratin-18 correlated with NASH . Among the 54 diabetic patients , NAFLD was found in 74 % and NASH in 22.2 % . CONCLUSION Prevalence of NAFLD and NASH is higher than estimated previously . Hispanics and patients with diabetes are at greatest risk for both NAFLD and NASH Introduction Nonalcoholic fatty liver disease ( NAFLD ) is the most common liver disease worldwide and is becoming the most frequent indication of liver transplantation . Cardiovascular disease is the main cause of death in these patients . There is no Food and Drug Association-approved medication for NAFLD patients . We aim ed to provide more robust evidence on the use of medications that are inexpensive and available , namely , metformin , silymarin , pioglitazone , and vitamin E , for treating NAFLD . Material s and methods We conducted a r and omized double-blinded , placebo-controlled trial on 150 consecutive patients with NAFLD who were assigned to five groups : lifestyle plus placebo , metformin 500 mg/day , silymarin 140 mg/day , pioglithasone 15 mg/day , and vitamin E 400 IU/day , all for 3 months  . Anthropometric and biochemical variables were measured at baseline and 3 months later . Results The mean age of the patients was 47.0±9.1 ( range : 18–65 ) years and the sex distribution was 73 ( 48.7 % ) women and 77 ( 51.3 % ) men . Patients in all groups showed a significant improvement in anthropometric parameters such as waist circumference and BMI . There was no statistically significant difference in alanine transaminase and aspartate transaminase in the control group after treatment ( P=0.51 , 0.18 , respectively ) ; however , both liver enzymes decreased significantly in the other groups . Discussion and conclusion This r and omized double-blinded placebo-controlled clinical trial suggested a significant benefit of silymarin , pioglitazone , and vitamin E in improving liver aminotransferases in patients with NAFLD after only 3 months , without exerting any specific side effects Objectives : This study aims to evaluate the effects of some probiotics on sonographic and biochemical nonalcoholic fatty liver disease ( NAFLD ) . Methods : This r and omized triple-blind trial was conducted among 64 obese children with sonographic NAFLD . They were r and omly allocated to receive probiotic capsule ( containing Lactobacillus acidophilus ATCC B3208 , 3 × 109 colony forming units [ CFU ] ; Bifidobacterium lactis DSMZ 32269 , 6 × 109 CFU ; Bifidobacterium bifidum ATCC SD6576 , 2 × 109 CFU ; Lactobacillus rhamnosus DSMZ 21690 , 2 × 109 CFU ) or placebo for 12 weeks . Results : After intervention , in the probiotic group the mean levels of alanine aminotransferase decreased from 32.8 ( 19.6 ) to 23.1 ( 9.9 ) U/L ( P = 0.02 ) and mean aspartate aminotransferase decreased from 32.2 ( 15.7 ) to 24.3 ( 7.7 ) U/L ( P = 0.02 ) . Likewise the mean cholesterol , low-density lipoprotein-C , and triglycerides as well as waist circumference decreased in the intervention group , without significant change in weight , body mass index , and body mass index z score . After the trial , normal liver sonography was reported in 17 ( 53.1 % ) and 5 ( 16.5 % ) of patients in the intervention and placebo groups , respectively . Conclusions : The present findings suggest that a course of the abovementioned probiotic compound can be effective in improving pediatric NAFLD OBJECTIVES : Nonalcoholic fatty liver disease ( NAFLD ) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis . Its prevalence has been found to be as high as 39 % . It is estimated that up to 15 % of those affected will go on to have progressive liver disease . Currently , there is no proven therapy for NAFLD . In this study , we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD . METHODS : In all , 1,005 men and women , aged 50–70 years were r and omized to receive either a daily combination of atorvastatin 20 mg , vitamin C 1 g , and vitamin E 1,000 IU vs. matching placebo , as part of the St Francis Heart Study r and omized clinical trial . Liver to spleen ( LS ) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence . Baseline and final LS ratios were compared within treatment groups , and results were compared between the treatment and placebo groups using univariate and multivariate analyses . Mean duration of follow-up was 3.6 years . RESULTS : There were 80 patients with NAFLD at baseline . We identified baseline triglyceride levels ( odds ratio (OR)=1.003 , P<0.001 ) and body mass index ( OR=0.10 , P<0.001 ) as independent correlates of NAFLD . Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up , 70 vs. 34 % ( OR=0.29 , P<0.001 ) . CONCLUSIONS : In conclusion , atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71 % in healthy individuals with NAFLD at baseline after 4 years of active therapy Summary Background Recent data suggest that the renin-angiotensin-aldosteron system ( RAAS ) may be of importance in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) . We were interested to investigate whether the therapy with RAAS blockers in patients with different stages of chronic kidney disease ( CKD ) has any effect on steatosis and fibrosis grade ; NAFLD documented by transient elastography ( TE ) ( Fibroscan ® -CAP ) . Methods Of 191 patients with various stages of CKD there were 61 patients with CKD grade III and IV , 62 patients with end-stage renal disease treated with chronic hemodialysis and 68 renal transplant recipients .  Liver stiffness was selected as the parameter to quantify liver fibrosis . Furthermore , the Controlled Attenuation Parameter ( CAP ) was used to detect and quantify liver steatosis with the help of TE . Results CKD patients ( p = 0.005 ) and CKD-NAFLD patients ( p = 0.0005 ) with angiotensin-converting enzyme inhibitors ( ACE-I ) or angiotensin receptor blockers ( ARBs ) had statistically significant lower degree of liver stiffness in comparison to those without these medications ( p = 0.005 ) . Also , we were interested to explore is there any difference in fibrosis and steatosis grade due to use of ACE-I or ARBs . We did not find statistically significant differences between those two subgroups of patients with respect to liver steatosis/fibrosis . Conclusion Based on our results , RAAS blockers could be an attractive option for the management of NAFLD . We believe that TE provides the opportunity of noninvasive screening of NAFLD in CKD patients . In further prospect i ve analysis , we believe that by using TE as noninvasive method we could investigate are ACE-I/ARBs really effective medications for the treatment of NAFLD in CKD patients .ZusammenfassungGrundlagenKürzlich berichtete Ergebnisse deuten darauf hin , dass das Renin-Angiotensin System ( RAAS ) von Bedeutung für die Pathogenese der nicht-alkoholischen Fettleber ( NAFLD ) sein könnte . Wir untersuchten , ob bei Patienten mit verschiedenen Stadien einer chronischen Nierenerkrankung ( CKD ) eine Therapie mit Blockern des RAAS eine Wirkung auf den Steatose- beziehungsweise Fibrose-Grad ( dokumentiert mittels transienter Elastographie ( TE ) – Fibroscan ® -CAP ) der Leber ausübt . Method ikEs wurden 191 Patienten mit verschiedenen Stadien der Niereninsuffizienz untersucht : 61 Patienten waren i m Stadium III der CKD , 62 Patienten waren i m Endstadium der Niereninsuffizienz und an der chronischen Hämodialyse , 68 Patienten waren Nierentransplantatempfänger . Als Parameter zur Quantifizierung der Leberfibrose wurde die Steifheit der Leber herangezogen . Außerdem wurde mit Hilfe der TE der „ Controlled Attenuation Parameter ( CAP ) “ zur Erkennung und Quantifizierung einer Steatose der Leber verwendet . ErgebnisseDie CKD Patienten ( p = 0,05 ) und die CKD-NAFLD Patienten ( p = 0,0005 ) , die mit ACE Hemmern oder Angiotensinrezeptorblockern beh and elt worden waren , hatten i m Vergleich zu den Patienten ohne diese Medikation einen statistisch signifikant niedrigeren Grad der Lebersteifheit . In Bezug auf die Steatose beziehungsweise den Fibrosegrad der Leber war kein statistisch signifikanter Einfluss der Medikation zu erheben . SchlussfolgerungUnsere Ergebnisse lassen den Schluss zu , dass RAAS Blocker eine attraktive Option beim Management der NAFLD sein könnten . Wir glauben , dass die TE eine Möglichkeit bietet , bei CKD Patienten nicht invasiv auf NAFLD zu screenen BACKGROUND Insulin resistance plays an important role in the pathogenesis of NAFLD . Pharmacological treatment of patients with NAFLD is still evolving . Insulin sensitizing drugs like metformin may be effective in these patients . Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases ( ALT ) after 6 months of lifestyle interventions and UDCA were treated with metformin 500 mg tid for 6 months . Insulin resistance was determined by HOMA- IR . Liver function tests were done monthly and patients were defined having no response , partial response or complete biochemical response depending on the change in ALT . Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions ( disease controls ) . RESULTS Thirteen ( 52 % ) patients had class III ( n = 5 ) or class IV ( n = 8) disease amounting to histological NASH . Of these 13 patients none had severe inflammation and none had stage 4 fibrosis ( cirrhosis ) . All 25 patients with NAFLD had insulin resistance in comparison to healthy controls . In comparison to disease controls ( 127.5 + /- 41.8 vs. 118 + /- 21.6 p = NS ) , all patients treated with metformin had partial biochemical response ( mean ALT 122.2 + /- 26.8 vs 74.3 + /- 4.2 p < 0.01 ) and 14 ( 56 % ) of them achieved complete normalization of ALT . CONCLUSIONS Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions  and UDCA
Conclusion Probiotic/synbiotic use  improves aminotransaminase levels and reduces proinflammatory marker high-sensitivity C-reactive protein and liver fibrosis in NAFLD patients
Background Nonalcoholic fatty liver disease ( NAFLD ) is the most prevalent chronic liver disease worldwide .
The pathogenesis of NAFLD is complex and multifactorial .
There is growing evidence that altered gut microbiota plays a key role in NAFLD progression .
Probiotics/synbiotics , by modifying gut microbiota , may be a promising treatment choice for NAFLD management .
Aim The aim of this study was to study the effect of probiotics/synbiotics on various laboratory and radiographic parameters in NAFLD management .