Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT). Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind Randomized Clinical Trial A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease. 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 Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial 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. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Enhanced Liver Fibrosis Test as a Reliable Tool for Assessing Fibrosis in Nonalcoholic Fatty Liver Disease in a Clinical Setting Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY) The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Ginger Supplementation in Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Pilot Study Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. The utility of radiological imaging in nonalcoholic fatty liver disease. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.
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 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 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 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 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 BACKGROUND Non-alcoholic fatty liver disease ( NAFLD ) and its advanced form non-alcoholic steatohepatitis ( NASH ) are the most common causes of elevated liver enzymes in the general population . NASH , and to a lesser extent NAFLD have been associated with increased liver-related , cardiovascular disease ( CVD ) , and allcause mortality . No effective treatment is widely acceptable . OBJECTIVE The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH . METHOD A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH . RESULTS Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial . Post hoc data from three large prospect i ve r and omized clinical trials ( n>11 , 000 ) suggest that specific statins ( mainly atorvastatin ) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function . Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH . Statin treatment may also protect from hepatocellular carcinoma ( HCC ) related to NAFLD/NASH . CONCLUSION Since NAFLD/NASH patients have high CVD risk , they will probably require a statin . Thus , why not select a specific statins ( atorvastatin or rosuvastatin , both generic now ) that offer a substantial liver- and CVDrelated adverse event reduction ? The administration of statins in these patients is as safe as in the general population 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 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 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 UNLABELLED Nonalcoholic fatty liver disease ( NAFLD ) covers a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis ( NASH ) , fibrosis , and cirrhosis . To date , no pharmacological treatment is approved for NAFLD/NASH . Here , we report on pre clinical and clinical data with GFT505 , a novel dual peroxisome proliferator-activated receptor alpha/delta ( PPAR-α/δ ) agonist . In the rat , GFT505 concentrated in the liver with limited extrahepatic exposure and underwent extensive enterohepatic cycling . The efficacy of GFT505 was assessed in animal models of NAFLD/NASH and liver fibrosis ( Western diet [WD]-fed human apolipoprotein E2 [ hApoE2 ] transgenic mice , methionine- and choline-deficient diet-fed db/db mice , and CCl4 -induced fibrosis in rats ) . GFT505  demonstrated liver-protective effects on steatosis , inflammation , and fibrosis . In addition , GFT505  improved liver dysfunction markers , decreased hepatic lipid accumulation , and inhibited proinflammatory ( interleukin-1 beta , tumor necrosis factor alpha , and F4/80 ) and profibrotic ( transforming growth factor beta , tissue inhibitor of metalloproteinase 2 , collagen type I , alpha 1 , and collagen type I , alpha 2 ) gene expression . To determine the role of PPAR-α-independent mechanisms , the effect of GFT505 was assessed in hApoE2 knock-in/PPAR-α knockout mice . In these mice , GFT505 also prevented WD-induced liver steatosis and inflammation , indicating a contribution of PPAR-α-independent mechanisms . Finally , the effect of GFT505 on liver dysfunction markers was assessed in a combined analysis of four phase II clinical studies in metabolic syndrome patients  . GFT505 treatment decreased plasma concentrations of alanine aminotransferase , gamma-glutamyl transpeptidase , and alkaline phosphatase . CONCLUSION The dual PPAR-α/δ agonist , GFT505 , is a promising liver-targeted drug for treatment of NAFLD/NASH . In animals , its protective effects are mediated by both PPAR-α-dependent and -independent mechanisms 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 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 The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population . We therefore performed a cross-sectional study in the town of Campogalliano ( Modena , Italy ) , within the context of the Dionysos Project . Of 5,780 eligible persons aged 18 to 75 years , 3,345 ( 58 % ) agreed to participate in the study . Subjects with suspected liver disease ( SLD ) , defined on the basis of elevated serum alanine aminotransferase ( ALT ) and gamma-glutamyl-transferase ( GGT ) activity , hepatitis B surface antigen ( HBsAg ) , or hepatitis C virus (HCV)-RNA positivity , were matched with r and omly selected subjects of the same age and sex without SLD . A total of 311 subjects with and 287 without SLD underwent a detailed clinical , laboratory , and anthropometrical evaluation . Fatty liver was diagnosed by ultrasonography , and alcohol intake was assessed by using a 7-day diary . Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease ( NAFLD ) and for alcoholic fatty liver ( AFLD ) versus NAFLD . The prevalence of NAFLD was similar in subjects with and without SLD ( 25 vs. 20 % , P = .203 ) . At multivariable analysis , normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity , hyperglycemia , hyperinsulinemia , hypertriglyceridemia , and systolic hypertension ; AFLD was more likely than NAFLD in older subjects , males , and in the presence of elevated GGT and hypertriglyceridemia , and less likely in the presence of obesity and hyperglycemia . In conclusion , NAFLD is highly prevalent in the general population , is not associated with SLD , but is associated with many features of the metabolic syndrome BACKGROUND / AIMS Insulin resistance is a common feature of both nonalcoholic fatty liver disease ( NAFLD ) and polycystic ovary syndrome ( PCOS ) , therefore , we hypothesize that PCOS and NAFLD may coexist . The aim of the present study was to determine the frequency and characteristics of NAFLD in women with PCOS . METHODS A prospect i ve study of patients with PCOS and no current pharmacological treatment was conducted . NAFLD was diagnosed by abdominal ultrasound following exclusion of alcohol consumption , viral , or autoimmune liver disease . Anthropometric variables , serum levels of glucose , insulin , lipids and aminotransferases , and HOMA index were determined . RESULTS Forty-one PCOS patients ( mean age : 24.6+/-7.2yr , mean body mass index [ BMI ] : 30.3+/-7.0kg/m(2 ) ) were included ; 26 of 41 PCOS patients ( 63.4 % ) had insulin resistance and 17 ( 41.5 % ) had NAFLD . Nine of the NAFLD patients ( 64 % ) also had abnormal aminotransferases .  Women with NAFLD and PCOS had a higher HOMA index and a higher waist-hip ratio than those with normal ultrasound . Patients with PCOS showed a higher frequency of NAFLD ( 41 % vs. 19 % ) and insulin resistance ( 63 % vs. 35.5 % ) than a control group . CONCLUSIONS NAFLD is frequent in patients with PCOS confirming a relevant clinical association between these two conditions . Women with PCOS should be screened for liver disease Background Liver fibrosis is the main determinant and predictor of the clinical course of nonalcoholic fatty liver disease ( NAFLD ) . To date , a liver biopsy is still considered the gold st and ard for staging fibrosis . The aim of this study was to investigate the diagnostic accuracy of the commercial enhanced liver fibrosis ( ELF ) test manufacturer 's cutoff value ( ≥9.8 ) in identifying severe fibrosis for adult patients with histologically confirmed NAFLD . Methods We tested the ELF test in a clinical practice , prospect i ve cohort of 82 consecutive patients who consecutively underwent percutaneous liver biopsy .  Results All stages of liver fibrosis were represented in our cohort , and severe fibrosis was present in 15 of 82 patients ( 18.3 % ) . The stage of fibrosis was significantly associated with ELF score ( Spearman 's rho = 0.483 , p<0.001 ) . The commercial ELF test manufacturer 's cutoff identified severe fibrosis with good sensitivity ( 86.7 % ; 95 % confidence interval [ 95 % CI ] , 0.69 - 1.04 ) and high specificity ( 92.5 % ; 95 % CI , 0.86 - 0.99 ) , with a positive predictive value of 72 % and negative predictive value of 97 % . Conclusions Our data could support the use of the ELF test in clinical practice Aim . This study compared the effects of telmisartan and losartan on  nonalcoholic fatty liver disease ( NAFLD )  and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus . Methods . This was a r and omized , open-label , parallel-group comparison of therapy with telmisartan or losartan .  Nineteen hypertensive NAFLD patients with type 2 diabetes were r and omly assigned to receive telmisartan at a dose of 20 mg once a day ( n = 12 ) or losartan at a dose of 50 mg once a day ( n = 7 ) for 12 months . Body fat area as determined by CT scanning and hepatic fat content based on the liver-to-spleen ( L/S ) ratio , as well as several parameters of glycemic and lipid metabolism , were compared before and after 12 months . Results . The telmisartan group showed a significant decline in serum free fatty acid ( FFA ) level ( from 0.87 ± 0.26 to 0.59 ± 0.22 mEq/L ( mean ± SD ) , P = 0.005 ) and a significant increase in L/S ratio ( P = 0.049 ) evaluated by CT scan , while these parameters were not changed in the losartan group . Conclusion . Although there was no significant difference in improvement in liver enzymes  with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months , it is suggested that telmisartan may exert beneficial effects by improving fatty liver BACKGROUND & AIMS We investigated the effects of the fatty acid-bile acid conjugate 3β-arachidyl-amido , 7α-12α-dihydroxy , 5β-cholan-24-oic acid ( Aramchol ; Trima Israel Pharmaceutical Products Ltd , Maabarot , Israel ) in a phase 2 trial of patients with nonalcoholic fatty liver disease ( NAFLD ) . METHODS We performed a r and omized , double-blind , placebo-controlled trial of 60 patients with biopsy-confirmed NAFLD ( 6 with nonalcoholic steatohepatitis ) at 10 centers in Israel . Patients were given Aramchol ( 100 or 300 mg ) or placebo once daily for 3 months ( n = 20/group ) . The main end point was the difference between groups in the change in liver fat content according to magnetic resonance spectroscopy . The secondary end points focused on the differences between groups in alterations of liver enzyme levels , levels of adiponectin , homeostasis model assessment scores , and endothelial function . RESULTS No serious or drug-related adverse events were observed in the 58 patients who completed the study . Over 3 months , liver fat content decreased by 12.57 % ± 22.14 % in patients given 300 mg/day Aramchol , but increased by 6.39 % ± 36.27 % in the placebo group ( P = .02 for the difference between groups , adjusted for age , sex , and body mass index ) . Liver fat content decreased in the 100-mg Aramchol group , by 2.89 % ± 28.22 % , but this change was nonsignificant ( P = .35 ) , indicating a dose-response relationship ( P for trend = .01 ) . Groups given Aramchol had nonsignificant improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin , but homeostasis model assessment scores did not change . The appropriateness of a single daily dose was confirmed by pharmacokinetic analysis . CONCLUSIONS Three months ' administration of the fatty acid-bile acid conjugate Aramchol is safe , tolerable , and significantly reduces liver fat content in patients with NAFLD . The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements , indicating that Aramchol might be used for the treatment of fatty liver disease . Clinical Trials.gov number : NCT01094158 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 BACKGROUND / AIMS To optimize management of nonalcoholic fatty liver disease ( NAFLD ) , a simple screening tool is necessary . In this study , we aim ed to devise a simple index of NAFLD . STUDY A cross-sectional study with 10,724 health check-up subjects ( 5362 cases with NAFLD versus age- and sex-matched controls ) was conducted . Study subjects were r and omly assigned to a derivation cohort or a validation cohort . RESULTS Multivariate analysis indicated that high serum alanine aminotransferase ( ALT ) to serum aspartate aminotransferase ( AST ) ratio , high body mass index ( BMI ) , and diabetes mellitus were independent risk factors of NAFLD ( all P<0.001 ) . Using these variables , a formula was derived by a logistic regression model : hepatic steatosis index (HSI)= 8 x(ALT/AST ratio)+ BMI ( + 2 , if female ; + 2 , if diabetes mellitus ) . HSI had an area under receiver-operating curve of 0.812 ( 95 % confidence interval , 0.801 - 0.824 ) . At values of < 30.0 or > 36.0 , HSI ruled out NAFLD with a sensitivity of 93.1 % , or detected NAFLD with a specificity of 92.4 % , respectively . Of 2692 subjects with HSI < 30.0 or > 36.0 in the derivation cohort , 2305 ( 85.6 % ) were correctly classified . HSI was vali date d in the subsequent validation cohort . CONCLUSION HSI is a simple , efficient screening tool for NAFLD that may be utilized for selecting individuals for liver ultrasonography and for determining the need for lifestyle modifications BACKGROUND & AIMS This prospect i ve study evaluates the role of radiological modalities in establishing the diagnosis of nonalcoholic steatohepatitis ( NASH ) . METHODS Consecutive patients with biopsy-proven nonalcoholic fatty liver disease ( NAFLD ) were enrolled ( 2000 - 2001 ) . Patients with other liver diseases and significant alcohol consumption ( > 20 g/day ) were excluded . Clinicodemographic data were gathered at the time of liver biopsy . Each biopsy specimen was assessed by a hepatopathologist . Each patient underwent a limited abdominal ultrasonography ( US ) , computerized tomography ( CT ) , and magnetic resonance imaging ( MRI ) . Films were interpreted by a radiologist who used a predetermined radiological protocol . Each radiological study was reread by the same radiologist and a second radiologist . RESULTS Patients with NASH had greater aspartate aminotransferase levels ( P = 0.03 ) , greater ferritin levels ( P = 0.05 ) , more hepatocyte ballooning ( P < 0.0001 ) , and more fibrosis ( P = 0.002 ) . None of the radiological features distinguished between NASH and other types of NAFLD . No radiological modality detected the presence of hepatocyte ballooning , Mallory 's hyaline , or fibrosis , which are important features in the diagnosis of NASH . The presence of > 33 % fat on liver biopsy was optimal for detecting steatosis on radiological imaging . CONCLUSIONS Differences between NASH and nonprogressive NAFLD were not apparent with any radiological modality . Of the pathologic features important for establishing the diagnosis of NASH , only the severity of steatosis was reflected in these radiological modalities . Good intraobserver agreement was evident for each modality ( US , CT , and MRI ) that was superior to interobserver agreement Nonalcoholic fatty liver disease ( NAFLD ) is the most common form of chronic liver disease in the pediatric population . Preliminary evidence suggests a potential therapeutic utility of probiotics for this condition . Here , we tested the potential effect of the probiotic VSL#3 ( a multistrain preparation composed of Streptococcus thermophilus and several species of Lactobacillus and Bifidobacteria ) on oxidative and inflammatory damage induced by a high-fat diet in the liver of young rats . At weaning , young male Sprague-Dawley rats were r and omly divided into 3 groups ( n = 6 ) fed a st and ard , nonpurified diet ( Std ; 5.5 % of energy from fat ) or a high-fat liquid diet ( HFD ; 71 % of energy from fat ) . One of the HFD groups received by gavage VSL#3 ( 13 x 10(9 ) bacteria x kg(-1 ) x d(-1 ) ) . After 4 wk , the HFD rats had greater body weight gain , fat mass , serum aminotransferase , and liver weight than rats fed the Std diet . The HFD induced liver lipid peroxidation , tumor necrosis factor ( TNFalpha ) production , protein S-nitrosylation , inducible nitric oxide synthase ( iNOS ) , cyclooxygenase (COX)-2 expression , and metalloproteinase ( MMP ) activity . Moreover , in the HFD group , PPARalpha expression was less than in rats fed the Std diet . In rats fed the HFD diet and treated with VSL#3 , liver TNFalpha levels , MMP-2 and MMP-9 activities , and expression of iNOS and COX-2 were significantly lower than in the HFD group . In VSL#3-treated rats , PPARalpha expression was greater than in the HFD group . A modulation of the nuclear factor-kappaB pathway by VSL#3 was also demonstrated . Our data suggest that VSL#3 administration could limit oxidative and inflammatory liver damage in patients with NAFLD 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
Conclusion The systematic review and meta- analysis support that probiotics are superior to placebo in NAFLD patients and could be utilized as a common complementary therapeutic approach
Background and Aims Probiotics was considered as a potential therapy for nonalcoholic fatty liver disease ( NAFLD ) without approval and comprehensive assessment in recent years , which call for a meta- analysis .