title: Effects of Probiotic and Prebiotic Supplementation on Leptin, Adiponectin, and Glycemic Parameters in Non-alcoholic Fatty Liver Disease: A Randomized Clinical Trial [Efficacy of probiotics on the treatment of non-alcoholic 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. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions: a comparison with more exhaustive strategies Effect of a Probiotic and Metformin on Liver Aminotransferases in Non-alcoholic Steatohepatitis: A Double Blind Randomized Clinical Trial Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Do symbiotic and Vitamin E supplementation have favorite effects in nonalcoholic fatty liver disease? A randomized, double-blind, placebo-controlled trial Probiotics administration following sleeve gastrectomy surgery: a randomized double-blind trial Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Retrieving randomized controlled trials from medline: a comparison of 38 published search filters. Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial. 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 Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind Randomized Clinical Trial Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non‐alcoholic steatohepatitis A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis Understanding why evidence from randomised clinical trials may not be retrieved from Medline: comparison of indexed and non-indexed records Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Combined effects of synbiotic and sitagliptin versus sitagliptin alone in patients with nonalcoholic fatty liver disease Daily Consumption of Synbiotic Yogurt Decreases Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease. Adiposity in relation to risks of fatty liver, cirrhosis and liver cancer: a prospective study of 0.5 million Chinese adults Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease
abstract: BACKGROUND According to previous studies , probiotic and prebiotic supplementation have desirable effects on glycemic parameters . Thus far , the effect of supplementation on the glycemic parameters and adipokines in non-alcoholic fatty liver disease ( NAFLD ) has not been assessed . Therefore , the aim of this study was to determine the effects of supplementation with probiotic and prebiotic on adiokines and glycemic parameters in the patients with NAFLD . METHODS In the present r and omized , double-blind , placebo-controlled trial , 89 patients with NAFLD were r and omly divided into three groups to receive one probiotic capsule + 16 g/d maltodextrin ( probiotic group ) or 16 g/d oligofructose powder + one placebo capsule ( prebiotic group ) , and one placebo capsule + 16 g/d maltodextrin ( control group ) for 12 weeks . All the subjects in the study were advised to follow the weight loss diet and physical activity recommendations during the intervention . Fasting blood sample s were taken at baseline and after the intervention to measure leptin , adiponectin , insulin , and fasting blood sugar . RESULTS At the end of the study , serum concentrations of leptin , insulin , and HOMA-IR decreased significantly in the probiotic and prebiotic groups compared with the control group . Despite the changes within the groups , serum concentrations of adiponectin did not change significantly between the three groups . Also , fasting blood sugar did not change between the groups , but decreased in the prebiotic group . Quantitative insulin-sensitivity check index ( QUICKI ) increased significantly in probiotic and prebiotic groups compared with the control group . CONCLUSION Probiotic and prebiotic supplementation along with lifestyle intervention has a favorable impact on glycemic parameters and leptin levels compared with lifestyle intervention alone Objective : To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease ( NAFLD ) . Methods : A total of 200 patients with NAFLD were r and omly divided into 4 groups : control group ( routine treatment group ) and combined treatment group A , B and C. Each group had equal patients . The control group received orally polyene phosphatidylcholine capsules ; whereas combined group A , B and C were given orally the live " combined Bifidobacterium Lactobacillus and Enterococcus powder " , " two live combined Bacillus subtilis and Enterococcus " , and the both probiotics respectively . The duration of treatment was 1 month . Laboratory parameters were evaluated before treatment and thirtieth day after treatment , including cholesterol ( TC ) , triglyceride ( TG ) , high density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol(LDL-C ) , alanine aminotransferase(ALT ) , aspartate aminotransferase ( AST ) , fasting blood glucose ( FPG ) , serum high molecular weight adiponectin ( HMW-APN ) and serum TNFα . Meanwhile the faece sample was collected for routine test and bacterial culture . Liver ultrasound scan was done in all patients . Results : In terms of blood lipids and blood glucose , each group improved after treatment with significant differences ( P<0.05 ) except for HDL-C. As for liver function , serum ALT and AST decreased after treatment in each group ; especially in combined group C which were lower than those of control group [ ( 33.7±7.6 ) U/L vs. ( 45.0±8.5 ) U/L ; ( 22.0±1.6 ) U/L vs. ( 29.4±3.7 ) U/L ; P<0.05 ] . TNFα levels decreased after treatment in each group , in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27 ) µg/L vs. ( 0.82±0.28 ) µg/L , P<0.05 ] . Serum HMW-APN increased after treatment in each group , and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72 ) µg/L vs. (7.87±3.96)µg/L , P<0.05 ] . ( 5 ) After treatment , all groups showed improvement of fatty liver by ultrasound , but the difference between groups was not statistically significant . ( 6 ) Compared with before treatment , fecal flora in combined groups was all reduced ( P<0.01 ) , but it was comparable before and after treatment in control group . Conclusions : Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin , possibly result ing in regulating blood glucose , lipid metabolism , and protecting liver injury from NAFLD BACKGROUND Probiotics have a beneficial effect on nonalcoholic fatty liver disease ( NAFLD ) in animal models . R and omized placebo-controlled trials ( RCTs ) in NAFLD are still lacking in humans despite a large number of data from animal research . AIM We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD . METHODS A total of 58 patients met the criteria for inclusion . They were r and omly assigned to receive the multi-probiotic " Symbiter " ( concentrated biomass of 14 probiotic bacteria genera Bifidobacterium , Lactobacillus , Lactococcus , Propionibacterium ) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment . The primary main outcomes were the changes in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in aminotransferase activity , serum lipids and cytokines ( TNF-α , IL-1β , IL-6 , IL-8 , and IFN-γ ) levels . Analysis of covariance was used to assess the difference between groups . RESULTS In the probiotic group , FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 ( p<0.001 ) but it did not change in the placebo group ( 82.57+/-2.45 to 81.6 + /-2.36 ; p=0.367 ) . In both groups a slight but not significant reduction of LS measured by SWE was detected . Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT . Among the markers of chronic systemic inflammatory state , only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic . CONCLUSION The probiotic " Symbiter "  reduces liver fat , aminotransferase activity , and the TNF-α and IL-6 levels in NAFLD patients . Modulation of the gut microbiota might represent a new therapy for NAFLD , which should be tested in larger studies BACKGROUND Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of synbiotic has been proposed as an effective treatment of NAFLD because of its modulating effect on the gut flora , which can influence the gut-liver axis . OBJECTIVE The objective was to evaluate the effects of supplementation with synbiotic on hepatic fibrosis , liver enzymes , and inflammatory markers in patients with NAFLD . DESIGN In a r and omized , double-blind , placebo-controlled clinical trial conducted as a pilot study , 52 patients with NAFLD were supplemented twice daily for 28 wk with either a synbiotic or a placebo capsule . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . RESULTS At the end of the study , the alanine aminotransferase ( ALT ) concentration decreased in both groups ; this reduction was significantly greater in the synbiotic group . At the end of the study , the following significant differences [ means ( 95 % CIs ) ] were seen between the synbiotic and placebo groups , respectively : ALT [ -25.1 ( -26.2 , -24 ) compared with -7.29 ( -9.5 , -5.1 ) IU/L ; P < 0.001 ] , aspartate aminotransferase [ -31.33 ( -32.1 , -30.5 ) compared with -7.94 ( -11.1 , -4.8 ) IU/L ; P < 0.001 ] , γ-glutamyltransferase [ -15.08 ( -15.5 , -14.7 ) compared with -5.21 ( -6.6 , -3.9 ) IU/L ; P < 0.001 ] , high-sensitivity C-reactive protein [ -2.3 ( -3 , -1.5 ) compared with -1.04 ( -1.5 , -0.6 ) mmol/L ; P < 0.05 ] , tumor necrosis factor-α [ -1.4 ( -1.7 , -1.1 ) compared with -0.59 ( -0.8 , -0.3 ) mmol/L ; P < 0.001 ] , total nuclear factor κ-B p65 [ -0.016 ( -0.022 , -0.011 ) compared with 0.001 ( -0.004 , -0.007 ) mmol/L ; P < 0.001 ] , and fibrosis score as determined by transient elastography [ - 2.98 ( -3.6 , -2.37 ) compared with -0.77 ( -1.32 , -0.22 ) kPa ; P < 0.001 ] . CONCLUSIONS Synbiotic supplementation in addition to lifestyle modification is superior to lifestyle modification alone for the treatment of NAFLD , at least partially through attenuation of inflammatory markers in the body . Whether these effects will be sustained with longer treatment duration s remains to be determined Non-alcoholic fatty liver disease ( NAFLD ) has been suggested to be well correlated with altered blood pressure . This study was conducted to determine the effects of symbiotic and vitamin E supplementation on blood pressure and inflammatory indices of patients with NAFLD . This r and omized , double-blind , placebo-controlled trial was performed among 60 NAFLD patients aged 25 to 64 years old . Participants were r and omly divided into four groups to receive a 400 IU alpha-tocopherol and 2 × 108 CFU/g symbiotic supplement for 8 weeks . The anthropometric parameters , systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) , serum malondialdehyde ( MDA ) , nitric oxide ( NO ) and tumor necrosis factor α ( TNFα ) were assessed at baseline and after 8 weeks of intervention . After 8 weeks of intervention , combined symbiotic and alpha-tocopherol , symbiotic and alpha-tocopherol alone administration , compared with the placebo , result ed in significant decreases in SBP ( -17.07±2.1 , -16.07±3.56 , -1.73±2.25 and -1.55±3.01 mmHg , P=0.01 ) , serum MDA ( -1.19±0.5 , -0.12±0.65 , 0.14 ± 0.64 and 0.16±0.34 nmol/mL , P<0.001 ) , serum TNFα ( -15.62±13.93 , -9.24±7.12 , -11.44 ± 15.47 and 3.01±1.71 pg/ml , P<0.001 ) concentrations . A significant decrease in serum AST ( -11.36±4.52 , -7.43±8.58 , -5.93±6.61 and 2.5±5.75 μmol/L , P < 0.001 ) , ALT ( -12.79±3.65 , -3.66±6.81 , -6.54±7.66 and 4.16±3.43 μmol/L , P < 0.001 ) and ALP ( -26.8±11.1 , -4.56±9.22 , -14.48±12.22 and 5.19±2.64 μmol/L , P < 0.001 ) was seen . Variations in DBP and serum NO concentration were not significant . Alpha-tocopherol and symbiotic supplementation among patients with NAFLD result ed in decreased SBP , serum MDA , TNFα levels and enzymes liver ; however , they did not affect DBP and serum NO concentration Background It is generally believed that exhaustive search es of bibliographic data bases are needed for systematic review s of health care interventions . The CENTRAL data base of controlled trials ( RCTs ) has been built up by exhaustive search ing . The CONSORT statement aims to encourage better reporting , and hence indexing , of RCTs . Our aim was to assess whether developments in the CENTRAL data base , and the CONSORT statement , mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic review s of health care interventions . Methods RCTs used in the Cochrane review s were identified . A brief RCT search strategy ( BRSS ) , consisting of a search of CENTRAL , and then for variants of the word r and om across all fields ( r and om$.af . ) in MEDLINE and EMBASE , was devised and run . Any trials included in the meta-analyses , but missed by the BRSS , were identified . The meta-analyses were then re-run , with and without the missed RCTs , and the differences quantified . The proportion of trials with variants of the word r and om in the title or abstract was calculated for each year . The number of RCTs retrieved by search ing with " r and om$.af . " was compared to the highly sensitive search strategy ( HSSS ) . Results The BRSS had a sensitivity of 94 % . It found all journal RCTs in 47 of the 57 review s. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five review s , but no important differences in conclusions result ed . In the post-CONSORT years , 1997–2003 , the percentage of RCTs with r and om in the title or abstract was 85 % , a mean increase of 17 % compared to the seven years pre-CONSORT ( 95 % CI , 8.3 % to 25.9 % ) . The search using r and om$.af . reduced the MEDLINE retrieval by 84 % , compared to the HSSS , thereby reducing the workload of checking retrievals . Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic review s in most cases . Exhaustive search ing is no longer cost-effective , because in effect it has already been done for CENTRAL Background : Non-alcoholic steatohepatitis ( NASH ) is a clinicopathological entity that is being recognized more frequently in recent years . This study aim ed to evaluate the effects of Metformin , with and without a probiotic supplement on liver aminotransferases in patients with NASH . Methods : Sixty four patients 18 - 75 years with NASH confirmed by biopsy and histological assessment were enrolled to study . Patients were r and omized to one of the following treatments for 6 months : Group I , probiotic ( Protexin two tablets per day ) plus Metformin 500 mg two tablets per day ( Met/Pro ) , or group II , Metformin 500 mg two tablets per day plus two placebo tablet ( Met/P ) . After 6 month alanine aminotransferase ( ALT ) , aspartate aminotransferase , and ultrasound grading of NASH were assessed . Results : In group I , serum alanine aminotransferase ( ALT : 133.7 ± 70 vs. 45.2 ± 32.5 ; P < 0.00 ) , and aspartate aminotransferase activity ( AST : 123.1 ± 72 vs. 44.2 ± 33.9 ; P < 0.001 ) , and ultrasound grading of NASH ( P < 0.001 ) all decreased significantly by the end of the treatment period . In group II , while serum alanine aminotransferase ( ALT ) was not significantly reduced ( 118.4 ± 67.9 vs. 112.5 ± 68.7 ; P < 0.064 ) , aspartate aminotransferase activity ( AST : 125.3 ± 71 vs. 113.4 ± 71 ; P < 0.001 ) , and ultrasound grading of NASH did fall significantly ( P < 0.01 ) . Body mass index ( BMI ) , fasting blood sugar ( FBS ) , cholesterol , and triglyceride fell significantly in both groups . Conclusions : Probiotic combination with Metformin improves liver aminotransferases better than metformin alone in patients with NASH Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries ; it can progress to nonalcoholic steatohepatitis ( NASH ) , cirrhosis and hepatocarcinoma . The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients . In a r and omized , controlled clinical trial , involving 50 biopsy-proven NASH patients , we investigated the effects of synbiotic supplementation on metabolic parameters , hepatic steatosis , intestinal permeability , small intestinal bacterial overgrowth ( SIBO ) and lipopolysaccharide ( LPS ) serum levels . Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone . Before and after the intervention we assessed steatosis by magnetic resonance imaging , intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing .  NASH patients presented high gut permeability , but low prevalence of SIBO . After the intervention , only the synbiotic group presented a reduction in steatosis , lost weight , diminished BMI and waist circumference measurement . Synbiotic did not improve intestinal permeability or LPS levels . We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients . This study was carried out to assess the effects of symbiotic and /or Vitamin E supplementation on liver enzymes , leptin , lipid profile , and some parameters of insulin resistance ( IR ) in NAFLD patients . Material s and Methods : We r and omly assigned sixty NAFLD adult patients to receive ( 1 ) symbiotic twice daily + Vitamin E-like placebo capsule ; ( 2 ) 400 IU/d Vitamin E + symbiotic-like placebo ; ( 3 ) symbiotic twice daily + 400 IU/d Vitamin E ; and ( 4 ) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks . Results : Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase ( P ≤ 0.05 ) . Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control . However , mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control . At the end of the study , significant differences in total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) were seen between the symbiotic plus Vitamin E and control groups ( P < 0.001 ) . Furthermore , intake of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides ( TG ) after the intervention . Significant differences in leptin , fasting blood sugar ( FBS ) , and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study ( P < 0.001 ) . In contrast , symbiotic and /or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels . Conclusion : In our study , symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes , leptin , FBS , insulin , TG , TC , and LDL-C among NAFLD patients Background : Probiotics are commonly used after bariatric surgery ; however , uncertainty remains regarding their efficacy . Our aim was to compare the effect of probiotics vs placebo on hepatic , inflammatory and clinical outcomes following  laparoscopic sleeve gastrectomy ( LSG ) . Methods : This r and omized , double-blind , placebo-controlled , trial of 6-month treatment with probiotics ( Bio-25 ; Supherb ) vs placebo and 6 months of additional follow-up was conducted among 100 morbidly obese nonalcoholic fatty liver disease ( NAFLD ) patients who underwent LSG surgery . The primary outcome was a reduction in liver fat content , measured by abdominal ultrasound , and secondary outcomes were improvement of fibrosis , measured by shear-wave elastography , metabolic and inflammatory parameters , anthropometrics and quality of life ( QOL ) . Fecal sample s were collected and analyzed for microbial composition . Results : One hundred patients ( 60 % women , mean age of 41.9±9.8 years and body mass index of 42.3±4.7 kg m−2 ) were r and omized , 80 % attended the 6-month visit and 77 % completed the 12-month follow-up . Fat content and NAFLD remission rate were similarly reduced in the probiotics and placebo groups at 6 months postsurgery ( −0.9±0.5 vs −0.7±0.4 score ; P=0.059 and 52.5 vs 40 % ; P=0.262 , respectively ) and at 12 months postsurgery . Fibrosis , liver-enzymes , C-reactive protein ( CRP ) , leptin and cytokeratin-18 levels were significantly reduced and QOL significantly improved within groups ( P⩽0.014 for all ) , but not between groups ( P⩾0.173 for all ) at 6 and 12 months postsurgery . Within- sample microbiota diversity ( alpha-diversity ) increased at 6-month postsurgery compared with baseline in both study arms ( P⩽0.008 ) and decreased again at 12 months postsurgery compared with 6 months postsurgery ( P⩽0.004 ) but did not reach baseline values . Conclusions : Probiotics administration does not improve hepatic , inflammatory and clinical outcomes 6- and 12 months post-LSG BACKGROUND Probiotics have profound effect on nonalcoholic steatohepatitis ( NASH ) in animal models . We aim ed to test the hypothesis that probiotics treatment was superior to usual care in reducing liver fat in NASH patients . MATERIAL AND METHODS Patients with histology-proven NASH were r and omized to receive probiotics ( n = 10 ) or usual care ( n = 10 ) for 6 months . The Lepicol probiotic formula contained Lactobacillus plantarum , Lactobacillus deslbrueckii , Lactobacillus acidophilus , Lactobacillus rhamnosus and Bifidobacterium bifidum . The primary endpoint was change in intrahepatic triglyceride content ( IHTG ) , as measured by proton-magnetic resonance spectroscopy , from baseline to month 6 . Secondary endpoints included changes in liver biochemistry and metabolic profile . RESULTS IHTG decreased from 22.6 ± 8.2 % to 14.9 ± 7.0 % in the probiotic group ( P = 0.034 ) but remained static in the usual care group ( 16.9 ± 6.1 % to 16.0 ± 6.6 % ; P = 0.55 ) . Six subjects in the probiotic group had IHTG reduced by more than 30 % from baseline , compared to 2 subjects in the usual care group ( P = 0.17 ) . The probiotic group also had greater reduction in serum aspartate aminotransferase level ( P = 0.008 ) . On the other h and , the use of probiotics was not associated with changes in body mass index , waist circumference , glucose and lipid levels . CONCLUSIONS Probiotics treatment may reduce liver fat and AST level in NASH patients . The therapeutic potential of probiotics in NASH should be tested in larger studies BACKGROUND People search medline for trials of healthcare interventions for clinical decisions , or to produce systematic review s , practice guidelines , or technology assessment s. Finding all relevant r and omized controlled trials ( RCTs ) with little extraneous material is challenging . OBJECTIVE To provide comparative data on the operating characteristics of search filters design ed to retrieve RCTs from medline . METHODS We identified 38 filters . The testing data base comprises h and search ing data from 161 clinical journals indexed in medline .  Sensitivity , specificity and precision were calculated . RESULTS The number of terms and operating characteristics varied considerably . Comparing the retrieval against the single term ' r and omized controlled trials.pt . ' ( sensitivity for retrieving RCTs , 93.7 % ) , 24 of 38 filters had statistically higher sensitivity ; 6 had a sensitivity of at least 99.0 % . Four other filters had specificities ( non retrieval of non- RCTs ) that were statistically not different or better than the single term ( 97.6 % ) . Precision was poor : only two filters had precision ( proportion of retrieved articles that were RCTs ) statistically similar to that of the single term (56.4%)-all others were lower . Filters with more search terms often had lower specificity , especially at high sensitivities . CONCLUSION Many RCT filters exist ( n = 38 ) . These comparative data can direct the choice of an RCT filter BACKGROUND Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease ( NAFLD ) . OBJECTIVE We examined whether overfeeding overweight subjects with simple sugars  increases liver fat and de novo lipogenesis ( DNL ) and whether this is reversible by weight loss . DESIGN Sixteen subjects [ BMI ( kg/m² ) : 30.6 ± 1.2 ] were placed on a hypercaloric diet ( > 1000 kcal simple carbohydrates/d ) for 3 wk and , thereafter , on a hypocaloric diet for 6 mo . The subjects were genotyped for rs739409 in the PNPLA3 gene . Before and after overfeeding and after hypocaloric diet , metabolic variables and liver fat ( measured by proton magnetic resonance spectroscopy ) were measured . The ratio of palmitate ( 16:0 ) to linoleate ( 18:2n-6 ) in serum and VLDL triglycerides was used as an index of DNL . RESULTS Carbohydrate overfeeding increased weight ( ±SEM ) by 2 % ( 1.8 ± 0.3 kg ; P < 0.0001 ) and liver fat by 27 % from 9.2 ± 1.9 % to 11.7 ± 1.9 % ( P = 0.005 ) . DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3 - 148IIbut not PNPLA3 - 148MM . During the hypocaloric diet , the subjects lost 4 % of their weight ( 3.2 ± 0.6 kg ; P < 0.0001 ) and 25 % of their liver fat content ( from 11.7 ± 1.9 % to 8.8 ± 1.8 % ; P < 0.05 ) . CONCLUSIONS Carbohydrate overfeeding for 3 wk induced a > 10-fold greater relative change in liver fat ( 27 % ) than in body weight ( 2 % ) . The increase in liver fat was proportional to that in DNL . Weight loss restores liver fat to normal . These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD . This trial was registered at www.hus.fi as 235780 OBJECTIVE The present pilot trial was carried out to evaluate the effects of an acute treatment with a mixture containing 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus per day in patients with non alcoholic fatty liver disease ( NAFLD ) . RESEARCH METHODS A sample of 30 patients with NAFLD ( diagnosed by liver biopsy ) was enrolled and 28 patients were analyzed in a double blind r and omized clinical trial . Patients were r and omized to one of the following treatments during 3 months : group I , treated with one tablet per day with 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus and group II , treated with one placebo tablet ( 120 mg of starch ) . RESULTS In group I , alanine amino transferase ( ALT : 67.7 + /- 25.1 vs. 60.4 + /- 30.4 UI/L ; p < 0.05 ) , aspartate aminotransferase activity ( AST : 41.3 + /- 15.5 vs. 35.6 + /- 10.4 UI/L ; p < 0.05 ) and gammaglutamine transferase levels ( gammaGT : 118.2 + /- 63.1 vs. 107.7 + /- 60.8 UI/L ; p < 0.05 ) decreased . In group II , all liver function parameters remained unchanged ( ALT : 60.7 + /- 32.1 vs. 64.8 + /- 35.5 UI/L ; p < 0.05 ) , aspartate aminotransferase activity ( AST : 31.7 + /- 13.1 vs. 36.4 + /- 13.8 UI/L ; ns ) and gammaglutamine transferase levels ( gammaGT : 82.1 + /- 55.1 vs. 83.6 + /- 65.3 UI/L ; ns ) . Anthropometric parameters and cardiovascular risk factors remained unchanged after treatment in both groups . CONCLUSION A tablet of 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus , with a r and omized clinical design , improved liver aminotransferases levels in patients with NAFLD 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 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 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 Long-term statin treatment reduces the frequency of cardiovascular events , but safety and efficacy in patients with abnormal liver tests is unclear . We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation ( GREACE ) study population . METHODS GREACE was a prospect i ve , intention-to-treat study that r and omly assigned by a computer-generated r and omisation list 1600 patients with coronary heart disease ( aged < 75 years , with serum concentrations of LDL cholesterol > 2·6 mmol/L and triglycerides < 4·5 mmol/L ) at the Hippokration University Hospital , Thessaloniki , Greece to receive statin or usual care , which could include statins .  The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests ( defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal ) compared with patients with abnormal liver tests who did not receive a statin . This risk reduction was compared with that for patients treated ( or not ) with statin and normal liver tests . FINDINGS Of 437 patients with moderately abnormal liver tests at baseline , which were possibly associated with non-alcoholic fatty liver disease , 227 who were treated with a statin ( mainly atorvastatin 24 mg per day ) had substantial improvement in liver tests ( p<0·0001 ) whereas 210 not treated with a statin had further increases of liver enzyme concentrations . Cardiovascular events occurred in 22 ( 10 % ) of 227 patients with abnormal liver tests who received statin ( 3·2 events per 100 patient-years ) and 63 ( 30 % ) of 210 patients with abnormal liver tests who did not receive statin ( 10·0 events per 100 patient-years ; 68 % relative risk reduction , p<0·0001 ) . This cardiovascular disease benefit was greater ( p=0·0074 ) than it was in patients with normal liver tests ( 90 [ 14 % ] events in 653 patients receiving a statin [ 4·6 per 100 patient-years ] vs 117 [ 23 % ] in 510 patients not receiving a statin [ 7·6 per 100 patient-years ] ; 39 % relative risk reduction , p<0·0001 ) . Seven ( < 1 % ) of 880 participants  who received a statin discontinued statin treatment because of liver-related adverse effects ( transaminase concentrations more than three-times the upper limit of normal ) . INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease . FUNDING None Gut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease ( NAFLD ) but r and omised controlled trials ( RCT ) are lacking in children BACKGROUND & AIMS : Silymarin is a complex mixture of 6 major flavonolignans and other minor polyphenolic compounds derived from the milk thistle plant Silybum marianum ; it has shown antioxidant , anti‐inflammatory and antifibrotic effects , and may be useful in patients with nonalcoholic fatty liver disease ( NAFLD ) . We aim ed to study the efficacy of silymarin in patients with nonalcoholic steatohepatitis (NASH)—the more severe form of NAFLD . METHODS : We performed a r and omized , double‐blind , placebo‐controlled trial of consecutive adults with biopsy‐proven NASH and a NAFLD activity score ( NAS ) of 4 or more at a tertiary care hospital in Kuala Lumpur , Malaysia , from November 2012 through August 2014 . Patients were r and omly assigned to groups given silymarin ( 700 mg ; n = 49 patients ) or placebo ( n = 50 patients ) 3 times daily for 48 weeks . After this 48‐week period , liver biopsies were repeated . The primary efficacy outcome was a decrease of 30 % or more in NAS ; findings from 48‐week liver biopsies were compared with those from the baseline biopsy . Secondary outcomes included changes in steatosis , lobular inflammation , hepatocyte ballooning , NAS and fibrosis score , and anthropometric measurements , as well as glycemic , lipid , and liver profiles and liver stiffness measurements . RESULTS : The percentage of patients achieving the primary efficacy outcome did not differ significantly between the groups ( 32.7 % in the silymarin group vs 26.0 % in the placebo group ; P = .467 ) . A significantly higher proportion of patients in the silymarin group had reductions in fibrosis based on histology ( reductions of 1 point or more ; 22.4 % ) than did the placebo group ( 6.0 % ; P = .023 ) , and based on liver stiffness measurements ( decrease of 30 % or more ; 24.2 % ) than did the placebo group ( 2.3 % ; P = .002 ) . The silymarin group also had significant reductions in mean aspartate aminotransferase to platelet ratio index ( reduction of 0.14 , P = .011 compared with baseline ) , fibrosis‐4 score ( reduction of 0.20 , P = .041 compared with baseline ) , and NAFLD fibrosis score ( reduction of 0.30 , P < .001 compared with baseline ) ; these changes were not observed in the placebo group ( reduction of 0.07 , P = .154 ; increase of 0.18 , P = .389 ; and reduction of 0.05 , P = .845 , respectively ) . There was no significant difference between groups in number of adverse events ; adverse events that occurred were not attributed to silymarin . CONCLUSIONS : In a r and omized trial of 99 patients , we found that silymarin ( 700 mg , given 3 times daily for 48 weeks ) did not reduce NAS scores by 30 % or more in a significantly larger proportion of patients with NASH than placebo . Silymarin may reduce liver fibrosis but this remains to be confirmed in a larger trial . It appears to be safe and well tolerated . Clinical Trials.gov : NCT02006498 Objective To explore why reports that seem to describe r and omised controlled trials are sometimes not indexed ( “ tagged ” ) with RCT ( r and omised controlled trial ) [ pt ] ( publication type ) in Medline . Design Cross sectional study . Setting The Cochrane Collaboration and US National Library of Medicine worked together to identify and retag records of r and omised controlled trials with RCT [ pt ] , 1994 to 2006 . Data source Published reports entered into Medline in 2005 . Main outcome measures Type of trial information presented ( for example , main results , design , and methods ) , trial design , and other Medline indexing terms applied . Results 572/591 ( 97 % ) untagged records and 578/594 ( 97 % ) tagged records contained information from r and omised controlled trials . Type of trial information and design differed between untagged and tagged reports . Fewer than half ( 234/572 , 41 % , 95 % confidence interval 37 % to 45 % ) of untagged reports but most tagged reports ( 526/578 , 91 % , 89 % to 93 % ) described the main results of the trial . Untagged reports were more likely than tagged reports to contain information on design and methods , baseline characteristics , long term follow-up , and secondary analyses . Untagged reports of main results were more likely than tagged reports to be from trials using a crossover design ( 36 % v 10 % , difference 25 % , 95 % confidence interval 19 % to 32 % ) . The Medical Subject Heading “ R and omized Controlled Trials ” was the most common clinical trial term applied to untagged reports , although more than half of untagged reports had no indexing related to trials . Conclusion Based on the results for 2005 , at least 3000 records describing r and omised controlled trials but not indexed using RCT [ pt ] may have been entered into Medline between 2006 and 2011 . Research ers and healthcare decision makers relying on using RCT [ pt ] may be missing important evidence in their search es , particularly for design and methods , baseline characteristics , long term follow-up , and secondary data analyses Although non-alcoholic fatty liver disease ( NAFLD ) is the leading aetiology of liver disorders in the world , there is no proven treatment for NAFLD patients with normal or low BMI . The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI . In this r and omised , double-blind , placebo-controlled , clinical trial , fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks . Both groups were advised to follow a healthy lifestyle . At the end of the study , hepatic steatosis and fibrosis reduced in both groups ; however , the mean reduction was significantly greater in the synbiotic group rather than in the placebo group ( P<0·001 ) . Furthermore , serum levels of fasting blood sugar , TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group ( P<0·05 ) . Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI , at least partially through reduction in inflammatory indices . Further studies are needed to address the exact mechanism of action of these effects Background / Aims Non-alcoholic fatty liver disease ( NAFLD ) is one of the most prevalent chronic liver diseases in recent years . The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD . Methods In total , 138 NAFLD patients aged 18 - 60 years were enrolled in the study . Patients were r and omized to one of the following treatments for 16 weeks : Group I ( n=68 ) , sitagliptin 50 mg daily plus placebo ( one capsule per day ) or group II ( n=70 ) sitagliptin 50 mg daily plus synbiotic ( one capsule per day ) . Changes in fasting blood glucose ( FBS ) , liver enzymes , lipid profile , and body mass index were compared between the groups . Results The mean change in FBS  with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL , and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups ( P<0.001 ) . The mean change in cholesterol ( Chol ) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic . There was a significant difference between the two groups ( P=0.029 ) . The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein ( LDL ) , whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL . A significant difference was observed between the two groups ( P<0.001 ) . On the other h and , in the sitagliptin-synbiotic group , there was significant improvement in aspartate aminotransferase ( AST ) level  compared to the sitagliptin-placebo group ( P=0.018 ) . Conclusions Sitagliptin-synbiotic produced greater improvement in FBS , AST , Chol , and LDL compared to sitagliptin alone in patients with NAFLD Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in developed and developing countries . The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD . Objective We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers , adipokine concentration , and gut peptide concentration as secondary outcomes in patients with NAFLD . Methods In this 24-wk , open-label , r and omized controlled clinical trial , 102 patients [ 50 men and 52 women ; mean age : 40 y ; body mass index ( in kg/m2 ) ( mean ± SD ) : 31.2 ± 4.9 ] were r and omly assigned to 3 groups , including 2 intervention groups and 1 control group . The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle ( i.e. , diet and exercise ) . The control group was advised to follow a healthy lifestyle alone . We evaluated differences between groups in liver function measures by using repeated- measures ANOVA , ANCOVA , and logistic regression . Results At the end of the study , the grade s of NAFLD , as determined by ultrasonography , showed a significant decrease in the synbiotic group compared with the conventional and control groups ( P < 0.001 ) . The following significant mean ± SD decreases were seen in the synbiotic , conventional , and control groups , respectively : serum concentration of alanine aminotransferase ( -14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L ; P = 0.008 ) , aspartate aminotransferase ( -7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L ; P < 0.001 ) , alkaline phosphatase ( -26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L ; P = 0.024 ) , and γ-glutamyltransferase ( -6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L ; P < 0.001 ) . Conclusion Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD . This trial was registered at the Iranian Registry of Clinical Trials website ( www.i rct .ir ) as I RCT 2017020932417N2 BACKGROUND The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease ( NAFLD ) . Hence , we performed a double-blind single center r and omized placebo-controlled trial ( RCT ) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD . METHODS A total of 48 patients met the criteria for inclusion . They were r and omly assigned to receive " Symbiter Omega " combination of probiotic biomass supplemented with flax and wheat germ oil ( 250 mg of each , concentration of omega-3 fatty acids 1 - 5 % ) or placebo for 8-weeks . The primary main outcomes were the change in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in transaminases level , serum lipids and cytokines levels . RESULTS In probiotic-omega group , FLI significantly decreased from 83.53±2.60 to 76.26±2.96 ( P<0.001 ) while no significant changes were observed in the placebo group ( 82.86±2.45 to 81.09±2.84 ; P=0.156 ) . Changes of LS in both groups were insignificant . Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase , triglycerides , and total cholesterol . Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group : IL-1β ( P=0.029 ) , TNF-α ( P<0.001 ) , IL-8 ( P=0.029 ) , IL-6 ( P=0.003 ) , and INF-γ ( P=0.016 ) . CONCLUSIONS Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat , improve serum lipids , metabolic profile , and reduce chronic systemic inflammatory state BACKGROUND 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 Adiposity is an increasing public health problem in China . We aim ed to examine the associations of adiposity with  non-alcoholic fatty liver disease ( NAFLD ) and other chronic liver diseases in Chinese adults . The prospect i ve China Kadoorie Biobank recruited 512,891 adults aged 30–79 years from 10 areas . During 10 years of follow-up , 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline . The mean body mass index ( BMI ) ( SD ) was 23.7 ( 3.3 ) kg/m2 and mean waist circumference ( WC ) 80.3 ( 9.8 ) cm , with 33 % having BMI ≥25 kg/m2 . Throughout the range examined ( BMI 15–50 ) BMI showed a log-linear positive association with NAFLD ( n = 1,298 ) , with adjusted HR per 5 kg/m2 of 2.81 ( 95 % CI 2.63–3.01 ) , adjusting for regression dilution . There were also positive associations of percent body fat , WC , and waist-to-hip ratio with NAFLD , with HRs per 1-SD of 2.27 ( 2.14–2.41 ) , 2.60 ( 2.44–2.76 ) , and 1.84 ( 1.76–1.92 ) . BMI was unrelated to viral hepatitis ( n = 1,477 ) , and had a U-shaped association with cirrhosis ( n = 2,082 ) and an inverse association with liver cancer ( n = 2,568 ) , which disappeared after excluding the first 5 years of follow-up . Among Chinese adults , adiposity was a major risk factor for NAFLD but not other chronic liver diseases 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
target: Conclusion : Probiotic treatment or supplementation is a promising therapeutic method for NAFLD
background: 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 .