Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind Randomized Clinical Trial Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT). 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 Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. The Role of Statins in the Management 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. Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease. Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety Utility of the ELF Test for Detecting Steatohepatitis in Morbid Obese Patients with Suspicion of Nonalcoholic Fatty Liver Disease Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. Effect of Aerobic and Resistance Exercise Training on Liver Enzymes and Hepatic Fat in Iranian Men With Nonalcoholic Fatty Liver Disease Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Ginger Supplementation in Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Pilot Study Daily Consumption of Synbiotic Yogurt Decreases Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial. Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY) Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial
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 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 : 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 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 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 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 & 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 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 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 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 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 The leading causes of mortality in nonalcoholic fatty liver disease ( NAFLD ) relate to cardiovascular disease ( CVD ) . The contribution of nitric oxide ( NO ) to endothelial function , a surrogate of CVD risk , is currently unknown in NAFLD . We hypothesize that NO-mediated cutaneous microvessel function would be impaired in NAFLD compared with controls and that exercise would enhance microvessel function compared with conventional care . Thirteen NAFLD patients ( aged 50 ± 3 yr , BMI 31 ± 1 kg/m² ) and seven controls ( 48 ± 4 yr , 30 ± 2 kg/m² ) were studied . NAFLD patients were r and omized to either 16 wk of exercise or conventional care . Cutaneous microvessel function was examined using laser Doppler flowmetry combined with intradermal microdialysis of N(G)-monomethyl-l-arginine to assay the NO dilator response to local forearm heating . Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat , respectively , and cardiorespiratory fitness was assessed . Differences in NO contribution to cutaneous blood flow between NAFLD and control individuals and between interventions were analyzed using general linear modeling . NO contribution to cutaneous blood flow was similar between NAFLD and controls ( P = 0.47 ) . Cardiorespiratory fitness was greater following exercise training compared with conventional care . NO contribution to cutaneous blood flow in response to heating at 42 ° C was 20.4 % CVCmax ( 95 % CI = 4.4 , 36.4 ) greater following exercise training compared with conventional care ( P = 0.02 ) . Exercise training  improves cutaneous microvascular NO function in NAFLD patients . The benefit of exercise training compared with conventional care strongly supports a role for exercise in the prevention of CVD in 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 and purpose Nonalcoholic fatty liver disease ( NAFLD ) is one of the causes of a fatty liver , occurring when fat is deposited ( steatosis ) in the liver not due to excessive alcohol use . It is related to insulin resistance and the metabolic syndrome . The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid ( ALA ) and ursodeoxycholic acid ( UDCA ) on NAFLD . Methods Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day ( ALAUDCA ) was investigated in patients over a period of 12 months using a r and omized , placebo (PLA)-controlled study with four parallel groups . Serum concentration of gamma-glutamyl transpeptidase ( GGT ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , albumin and platelets ( PLT ) were measured at the beginning and at the end of the treatment . Moreover , the AST/ALT ratio and the NAFLD fibrosis score were examined . Results A total of 120 patients were r and omly assigned to the four groups . ALA and UDCA were safe and well tolerated in the oral daily administration only . AST , ALT , GGT ( p < 0.001 ) showed a significant difference between ALAUDCA and other three groups . Besides , NAFLD fibrosis score underlined a significant reduction ( p < 0.04 ) in the ALAUDCA group , while AST/ALT ratio presented a moderate decline ( p > 0.05 ) . Conclusion ALAUDCA therapy reduced AST , ALT , GGT values and improved NAFLD fibrosis score and AST/ALT ratio , especially in patients who were on a hypocaloric diet . These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies 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 and aims : Nonalcoholic fatty liver disease ( NAFLD ) is now recognized as part of the metabolic syndrome , and is specifically related to obesity and insulin resistance . Lifestyle modification is advocated for the treatment of NAFLD , but few studies have evaluated its impact on liver histology . The purpose of this study was to investigate which , if any , specific diet and exercise recommendations are associated with histopathologic changes . Methods : A total of 56 participants were r and omly assigned to 1 of 4 lifestyle modification subgroups for 6 months : st and ard care , low-fat diet and moderate exercise , moderate-fat/low-processed-carbohydrate diet and moderate exercise , or moderate exercise only .  All subjects had biopsy-proven NAFLD , to include nonalcoholic steatohepatitis ( NASH ) , and received a repeat 6-month biopsy to detect histopathologic changes . Other measures included blood assay of liver enzymes ( aspartate aminotransferase , alanine aminotransferase , alkaline phosphatase ) , fasting glucose , serum insulin , lipid panel , body weight , dietary intake , fat mass , and fitness level . Results : Among the 41 participants who completed the study ( 88 % with NASH ) , a significant change was found in pre- to post-NAFLD activity score in the group as a whole ( p < 0.001 ) with no difference detected between subgroups ( p = 0.31 ) . Our results confirm that lifestyle modification is effective in improving NAFLD and NASH . Conclusions : Regardless of intervention group , lifestyle modification improved liver histology , as verified by repeat biopsy , after a 6-month intervention . This study reinforces the importance of lifestyle modification as the primary treatment strategy for patients with NAFLD Non-alcoholic fatty liver disease ( NAFLD ) is the most common liver disorder in Western industrialized countries , affecting 20 - 40 % of the general population . Large population -based surveys in China , Japan , and Korea indicate that the prevalence of NAFLD is now 12 % to 24 % in population subgroups , depending on age , gender , ethnicity , and location ( urban versus rural ) . There is strong evidence that the prevalence of NAFLD has increased recently in parallel with regional trends in obesity , type 2 diabetes , and metabolic syndrome ; and that further increases are likely . The relationship between NAFLD , central obesity , diabetes , and metabolic syndrome is clearly evident in retrospective and prospect i ve Asian studies , but the strength of association with these metabolic risk factors is only appreciated when regional definitions of anthropometry are used . Pathological definition of NAFLD , particularly its activity and the extent of liver fibrosis , requires histological examination , but liver biopsy is often not appropriate in this disorder for logistic reasons . An alternative set of operational definitions is proposed here . Clinicians need guidelines as how best to diagnose and manage NAFLD and its associated metabolic disorders in countries with scant healthcare re sources . The Asia-Pacific Working Party ( APWP ) for NAFLD was convened to collate evidence and deliberate these issues . Draft proposals were presented and discussed at Asia-Pacific Digestive Week at Cebu , Philippines , in late November 2006 , and are published separately in this issue of the Journal as an Executive Summary . The present document review s the reasoning and evidence behind the APWP-NAFLD proposals for definition , assessment , and management of NAFLD in the Asia-Pacific region Background : Nonalcoholic fatty liver disease ( NAFLD ) has different prevalence rates in various parts of the world and is a risk factor for diabetes and cardiovascular disease that could progress to nonalcoholic steatohepatitis , cirrhosis , and liver failure . Objectives : The current study aim ed to investigate the effect of Aerobic Training ( AT ) and resistance training ( RT ) on hepatic fat content and liver enzyme levels in Iranian men . Patients and Methods : In a r and omized clinical trial study , 30 men with clinical ly defined NAFLD were allocated into three groups ( aerobic , resistance and control ) . An aerobic group program consisted of 45 minutes of aerobic exercise at 60 % - 75 % maximum heart rate intensity , a resistance group performed seven resistance exercises at intensity of 50 % - 70 % of 1 repetition maximum ( 1RM ) and the control group had no exercise training program during the study . Before and after training , anthropometry , insulin sensitivity , liver enzymes and hepatic fat were elevated . Results : After training , hepatic fat content was markedly reduced , to a similar extent , in both the aerobic and resistance exercise training groups ( P ≤ 0.05 ) . In the two exercise training groups , alanine amino transferase and aspartate amino transferase serum levels were significantly decreased compared to the control group ( P = 0.002 ) and ( P = 0.02 ) , respectively . Moreover , body fat ( % ) , fat mass ( kg ) , homeostasis model assessment insulin resistance ( HOMI-IR ) were all improved in the AT and RT . These changes in the AT group were independent of weight loss . Conclusions : This study demonstrated that RT and AT are equally effective in reducing hepatic fat content and liver enzyme levels among patients with NAFLD . However , aerobic exercise specifically improves NAFLD independent of any change in body weight Purpose : Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) , antioxidant approaches have not been sufficiently investigated in human NAFLD management . Resveratrol has been reported to possess a wide range of biological functions , including antioxidant activities . This study aim ed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD . Methods : This r and omized , double-blind , placebo-controlled clinical trial was conducted on 60 patients with NAFLD ( males and females ) aged 20 to 60 years , and body mass index ( BMI ) of 25 - 35 kg/m2 . Subjects were r and omly assigned to receive a daily dose of 600 mg resveratrol ( 2 × 300 mg pure trans-resveratrol capsules ; n=30 ) or placebo capsules ( n=30 ) for 12 wk . Fasting blood sample s , anthropometric measurements , and dietary intakes were collected for all patients at baseline and at the end of the trial . Oxidative stress was evaluated by measurement of serum malondialdehyde ( MDA ) , oxidized low-density lipoprotein ( ox-LDL ) , total antioxidant capacity ( TAC ) , and erythrocyte superoxide dismutase ( SOD ) as well as glutathione peroxidase ( GSH-Px ) activities . Changes in the outcomes were analyzed using analysis of covariance ( ANCOVA ) . Results : Resveratrol supplementation did not significantly affect neither serum MDA , ox-LDL , and TAC levels , nor erythrocyte SOD and GSH-Px activities , compared to placebo group ( All P>0.05 ) . Moreover , changes in serum levels of liver enzymes ( ALT , AST , GGT , and ALP ) were not significant in neither of the study groups ( All P>0.05 ) . Conclusion : Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD In the absence of surrogate markers , the evaluation of suspected nonalcoholic fatty liver disease ( NAFLD ) is highly dependent on histological examination . The extent of sampling variability affecting the reliability of a single liver biopsy in patients with suspected NAFLD is poorly characterized . This prospect i ve study aim ed to correlate precise histological findings in paired biopsies — right and left lobe — in the diagnosis of NAFLD in morbidly obese subjects undergoing bariatric surgery  employing both Brunt and Matteoni classifications and the NAFLD Activity Score ( NAS ) . We also aim ed to determine whether the composite histopathological findings of the two biopsies would improve diagnostic accuracy . Consecutive subjects had an intraoperative biopsy from both right and left lobes , evaluated and scored in a blinded manner . Intraobserver agreement was also assessed . Kappa coefficients of agreement were calculated . Forty‐one subjects had acceptable biopsies . Agreement for steatosis was excellent and moderate for fibrosis . Concordance was only fair for most features of necroinflammation . Intraobserver agreement was only moderate for lobular inflammation . Excellent agreement was seen for the diagnosis of NASH using Brunt criteria and good agreement when using Matteoni and NAS scoring systems . Composite biopsy data particularly improved identification of hepatocyte ballooning . The diagnostic accuracy also improved substantially when composite features were compared with single‐sided biopsy features , especially for the Matteoni and NAS scoring systems . In conclusion , significant sampling variability occurs in NAFLD , particularly for features of necroinflammation . This should be factored into the design of clinical trials and studies of the natural history of the disease . ( HEPATOLOGY 2006;44:874–880 . Nonalcoholic fatty liver disease ( NAFLD ) is the most prevalent cause of hepatic injury in the world . One of the most important therapeutic strategies for this disease is modulating insulin resistance and oxidative stress . In this study , we investigated the hypothesis that supplementation with cinnamon exerts an insulin sensitizer effect in patients with NAFLD . In a double-blind , placebo-controlled trial with two parallel groups , fifty patients with NAFLD were r and omized to receive daily supplementation with either two capsules of cinnamon ( each capsule contain 750 mg cinnamon ) or 2 placebo capsules , daily for 12 weeks . During the intervention , all patients were given advice on how to implement a balanced diet and physical activity into their daily lives . In the treatment group ( P < .05 ) , significant decreases in HOMA ( Homeostatic Model Assessment ) index , FBS ( fasting blood glucose ) , total cholesterol , triglyceride , ALT ( alanine aminotransferase ) , AST ( aspartate aminotransferase ) , GGT ( gamma glutamine transpeptidase ) , and high-sensitivity C-reactive protein were seen , but there was no significant change in serum high-density lipoproteins levels ( P = .122 ) . In both groups , low-density lipoproteins decreased significantly ( P < .05 ) . In conclusion , the study suggests that taking 1500 mg cinnamon daily may be effective in improving NAFLD characteristics 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 The only currently recommended treatment for nonalcoholic fatty liver disease ( NAFLD ) is lifestyle modification . Preliminary studies of silybin showed beneficial effects on liver function .  Realsil ( RA ) comprises the silybin phytosome complex ( silybin plus phosphatidylcholine ) coformulated with vitamin E. We report on a multicenter , phase III , double-blind clinical trial to assess RA in patients with histologically documented NAFLD . Patients were r and omized 1:1 to RA or placebo ( P ) orally twice daily for 12 months . Prespecified primary outcomes were improvement over time in clinical condition , normalization of liver enzyme plasma levels , and improvement of ultrasonographic liver steatosis , homeostatic model assessment ( HOMA ) , and quality of life . Secondary outcomes were improvement in liver histologic score and /or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines , ferritin , and liver fibrosis markers .  We treated 179 patients with NAFLD ; 36 were also HCV positive . Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol ( 69 per group ) . Baseline patient characteristics were generally well balanced between groups , except for steatosis , portal infiltration , and fibrosis . Adverse events ( AEs ) were generally transient and included diarrhea , dysgeusia , and pruritus ; no serious AEs were recorded . Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels , HOMA , and liver histology . Body mass index normalized in 15 % of RA patients ( 2.1 % with P ) . HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers . This is the first study to systematic ally assess silybin in NAFLD patients . Treatment with RA but not P for 12 months was associated with improvement in liver enzymes , insulin resistance , and liver histology , without increases in body weight . These findings warrant further investigation 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 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 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 : Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease ( NAFLD ) . However , the effects of zinc and selenium co-supplementation before and /or after disease progression on NAFLD are not clear enough . The aim of this study was to compare the effects of zinc and selenium co-supplementation before and /or after disease progression on NAFLD prognosis . Material s and Methods : Forty male Sprague – Dawley rats ( 197±4 g ) were r and omly assigned to 4 dietary groups : normal-fat diet ( NFD ; receiving 9 % of calories as fat ) , high-fat diet ( HFD ; receiving 82 % of calories as fat ) , supplementation before disease progression ( S+HFD ) , and supplementation after disease progression ( HFD+S ) . The diets were implemented over a 20-week period in all the groups . Biochemical and histologic parameters were compared between the 4 groups , and between-group comparisons were also carried out . Results : There were significant differences in the average food dietary intake ( P<0.001 ) , weight ( P<0.001 ) , fasting blood sugar ( P=0.005 ) , triglyceride ( P<0.001 ) , total cholesterol ( P<0.001 ) , low-density lipoprotein cholesterol ( P=0.002 ) , high-density lipoprotein cholesterol ( P=0.001 ) , alanine aminotransferase ( P<0.001 ) , and aspartate aminotransferase ( P<0.001 ) between the 4 dietary groups . Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group ( P<0.001 and P=0.003 , respectively ) . Fat accumulation was significantly reduced in the HFD+S Group ( P<0.001 ) . Conclusion : Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD Background : Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common hepatic diseases in the general adult population . Dyslipidemia , hyperuricemia , and insulin resistance are common risk factors and accompanying features of NAFLD . Curcumin is a dietary natural product with beneficial metabolic effects relevant to the treatment of NAFLD . Aim : To assess the effects of curcumin on metabolic profile in subjects with NAFLD . Methods : Patients diagnosed with NAFLD ( grade s 1–3 ; according to liver sonography ) were r and omly assigned to curcumin ( 1000 mg/d in 2 divided doses ) ( n = 50 ) or control ( n = 52 ) group for a period of 8 weeks . All patients received dietary and lifestyle advises before the start of trial . Anthropometric measurements , lipid profile , glucose , insulin , glycated hemoglobin , and uric acid concentrations were measured at baseline and after 8 weeks of follow-up . Results : Eighty-seven subjects ( n = 44 and 43 in the curcumin and control group , respectively ) completed the trial . Supplementation with curcumin was associated with a reduction in serum levels of total cholesterol ( P < 0.001 ) , low-density lipoprotein cholesterol ( P < 0.001 ) , triglycerides ( P < 0.001 ) , non – high-density lipoprotein cholesterol ( P < 0.001 ) , and uric acid ( P < 0.001 ) , whereas serum levels of high-density lipoprotein cholesterol and glucose control parameters remained unaltered . Curcumin was safe and well tolerated during this study . Conclusion : Results of the present trial suggest that curcumin supplementation reduces serum lipids and uric acid concentrations in patients with 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
Conclusion : Probiotic treatment or supplementation is a promising therapeutic method for NAFLD
Background : Nonalcoholic fatty liver disease ( NAFLD ) has become prevalent in recent decades , especially in developed countries , and approaches for the prevention and treatment of NAFLD are not clear .
The aim of this research was to analyze and summarize r and omized controlled trials that investigated the effects of probiotics on NAFLD .