Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT). Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial 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. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled 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 Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions. Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.
Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease ( NAFLD ) to shift into one of the most frequent causes of chronic liver illness in childhood . Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used ; overall it ranges between 3 % and 10 % of pediatric population , increasing up to 70 % in patients with metabolic comorbidities ( Manco M , Bottazzo G , DeVito R et al , J Am Coll Nutr 27:667 - 676 , 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions , including type 2 diabetes ( T2D ) , obesity , and nonalcoholic steatohepatitis ( NASH ) . One of the emerging areas of the study is the link between liver diseases and gut microbiome , which has added new information to the underst and ing of the so-called gut-liver axis . In order to address the role of gut microbiome in NAFLD onset and progression , it is necessary to " decipher " operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and , hence , to address the function of the intestinal microbiome within the gut microbiota-liver axis . Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of  obesity and NAFLD in adults and children . Several r and omized clinical trials ( RCTs ) have been already published on  fecal microbiota transplantation  ( FMT ) , T2D , NASH , and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions , probiotics , symbiotics , and FMT Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease ( NAFLD ) . But it remains unknown in nonobese NAFLD . This prospect i ve , cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression . A total of 126 nonobese subjects were enrolled : 43 NAFLD and 83 healthy controls ( HC ) . The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region . Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD . Compared with HC , patients had 20 % more phylum Bacteroidetes ( p = 0.005 ) and 24 % less Firmicutes ( p = 0.002 ) . Within Firmicutes , four families and their 8 genera , which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria , were significantly decreased . Moreover , Gram-negative ( G− ) bacteria were prevalent in NAFLD ( p = 0.008 ) . Furthermore , a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD . This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression Background 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 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 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 Healthy lifestyle is the most important management of non-alcoholic fatty liver disease ( NAFLD ) . This study aim ed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD . METHODS This was a parallel group , superiority , r and omized controlled trial . 154 adults with NAFLD identified during population screening were r and omized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months . The primary outcome was remission of NAFLD at month 12 as evidence d by intrahepatic triglyceride content ( IHTG ) of less than 5 % by proton-magnetic resonance spectroscopy . RESULTS 74 patients in the intervention group and 71 patients in the control group completed all study assessment s. In an intention-to-treat analysis of all 154 patients , 64 % of the patients in the intervention group and 20 % in the control group achieved remission of NAFLD ( difference between groups 44 % ; 95 % CI 30 - 58 % ; p<0.001 ) . The mean ( SD ) changes in IHTG from baseline to month 12 were -6.7 % ( 6.1 % ) in the intervention group and -2.1 % ( 6.4 % ) in the control group ( p<0.001 ) . Body weight decreased by 5.6 ( 4.4 ) kg and 0.6 ( 2.5 ) kg in the two groups , respectively ( p<0.001 ) . While 97 % of patients with weight loss of more than 10 % had remission of NAFLD , 41 % of those with weight loss of 3.0 - 4.9 % could also achieve the primary outcome . CONCLUSIONS The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients Objective : Nonalcoholic fatty liver disease ( NAFLD ) is a condition defined by exceeding triglycerides accumulation in the liver . The condition can develop into fibrosis , cirrhosis , and hepatocellular carcinoma . Considering the ever-increasing prevalence of NAFLD , the aim of the present study was to investigate the effects of probiotic supplementation on glycemic and inflammatory indices in patients with NAFLD . Methods : This r and omized clinical trial was conducted on 42 patients with NAFLD who had been referred to a gastroenterology clinic . Subjects in the intervention and control groups consumed 2 capsules/day probiotic or placebo , respectively , for 8 weeks . Fasting blood sugar ( FBS ) , insulin , insulin resistance , tumor necrosis factor alpha ( TNF-α ) , and interleukin 6 ( IL-6 ) were measured at baseline and at the end of the study . Results : Means of FBS , insulin , insulin resistance , and IL-6 were significantly different between groups after intervention ( p < 0.05 ) , whereas TNF-α was not significantly modified ( p > 0.05 ) . In the probiotic group , insulin , insulin resistance , TNF-α , and IL-6 decreased significantly at the end of the study compared to the beginning of study . Conclusion : Considering the effects of probiotic supplementation on the reduction of glycemic and inflammatory indices in patients with NAFLD , consumption of probiotics is recommended as a complementary therapy in these patients 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 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 . 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 Purpose In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat . In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis ( NASH ) , a disease marked by hepatic inflammation and fibrosis . Although the precise pathophysiology of NASH is unknown , it is believed that the gut microbiota-liver axis influences the development of this disease . With few treatment strategies available for NASH , exploration of gut microbiota-targeted interventions is warranted . We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH . Methods In a placebo-controlled , r and omized pilot trial , 14 individuals with liver-biopsy-confirmed NASH [ non-alcoholic fatty liver activity score ( NAS ) ≥ 5 ] were r and omized to receive oligofructose ( 8 g/day for 12 weeks followed by 16 g/day for 24 weeks ) or isocaloric placebo for 9 months . The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight , body composition , glucose tolerance , inflammatory markers , and gut microbiota . Results Independent of weight loss  , oligofructose improved liver steatosis relative to placebo and improved overall NAS score ( P = 0.016 ) . Bifidobacterium was enhanced by oligofructose , whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose ( P < 0.05 ) . There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease . Conclusions Independent of other lifestyle changes , prebiotic supplementation  reduced histologically-confirmed steatosis in patients with NASH . Larger follow-up studies are warranted . Clinical TrialThis trial was registered at Clinical trials.com as NCT03184376 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 The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population . We therefore performed a cross-sectional study in the town of Campogalliano ( Modena , Italy ) , within the context of the Dionysos Project . Of 5,780 eligible persons aged 18 to 75 years , 3,345 ( 58 % ) agreed to participate in the study . Subjects with suspected liver disease ( SLD ) , defined on the basis of elevated serum alanine aminotransferase ( ALT ) and gamma-glutamyl-transferase ( GGT ) activity , hepatitis B surface antigen ( HBsAg ) , or hepatitis C virus (HCV)-RNA positivity , were matched with r and omly selected subjects of the same age and sex without SLD . A total of 311 subjects with and 287 without SLD underwent a detailed clinical , laboratory , and anthropometrical evaluation . Fatty liver was diagnosed by ultrasonography , and alcohol intake was assessed by using a 7-day diary . Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease ( NAFLD ) and for alcoholic fatty liver ( AFLD ) versus NAFLD . The prevalence of NAFLD was similar in subjects with and without SLD ( 25 vs. 20 % , P = .203 ) . At multivariable analysis , normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity , hyperglycemia , hyperinsulinemia , hypertriglyceridemia , and systolic hypertension ; AFLD was more likely than NAFLD in older subjects , males , and in the presence of elevated GGT and hypertriglyceridemia , and less likely in the presence of obesity and hyperglycemia . In conclusion , NAFLD is highly prevalent in the general population , is not associated with SLD , but is associated with many features of the metabolic syndrome BACKGROUND Insulin resistance plays an important role in the pathogenesis of NAFLD . Pharmacological treatment of patients with NAFLD is still evolving . Insulin sensitizing drugs like metformin may be effective in these patients . Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases ( ALT ) after 6 months of lifestyle interventions and UDCA were treated with metformin 500 mg tid for 6 months . Insulin resistance was determined by HOMA- IR . Liver function tests were done monthly and patients were defined having no response , partial response or complete biochemical response depending on the change in ALT . Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions ( disease controls ) . RESULTS Thirteen ( 52 % ) patients had class III ( n = 5 ) or class IV ( n = 8) disease amounting to histological NASH . Of these 13 patients none had severe inflammation and none had stage 4 fibrosis ( cirrhosis ) . All 25 patients with NAFLD had insulin resistance in comparison to healthy controls . In comparison to disease controls ( 127.5 + /- 41.8 vs. 118 + /- 21.6 p = NS ) , all patients treated with metformin had partial biochemical response ( mean ALT 122.2 + /- 26.8 vs 74.3 + /- 4.2 p < 0.01 ) and 14 ( 56 % ) of them achieved complete normalization of ALT . CONCLUSIONS Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions  and UDCA 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 The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease ( NAFLD ) . Hence , we performed a double-blind single center r and omized placebo-controlled trial ( RCT ) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD . METHODS A total of 48 patients met the criteria for inclusion . They were r and omly assigned to receive " Symbiter Omega " combination of probiotic biomass supplemented with flax and wheat germ oil ( 250 mg of each , concentration of omega-3 fatty acids 1 - 5 % ) or placebo for 8-weeks . The primary main outcomes were the change in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in transaminases level , serum lipids and cytokines levels . RESULTS In probiotic-omega group , FLI significantly decreased from 83.53±2.60 to 76.26±2.96 ( P<0.001 ) while no significant changes were observed in the placebo group ( 82.86±2.45 to 81.09±2.84 ; P=0.156 ) . Changes of LS in both groups were insignificant . Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase , triglycerides , and total cholesterol . Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group : IL-1β ( P=0.029 ) , TNF-α ( P<0.001 ) , IL-8 ( P=0.029 ) , IL-6 ( P=0.003 ) , and INF-γ ( P=0.016 ) . CONCLUSIONS Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat , improve serum lipids , metabolic profile , and reduce chronic systemic inflammatory state
Conclusion This meta- analysis supports the potential use of microbial therapies in the treatment of NAFLD and sheds light on their potential mode of action .
Context Nonalcoholic fatty liver disease ( NAFLD ) is a highly prevalent and underdiagnosed comorbidity of many chronic diseases that is associated with altered intestinal bacterial communities .
This association has prompted research into alternative treatments aim ed at modulating intestinal microbiota .
Given the novelty of these treatments , scarce evidence regarding their effectiveness in clinical population s exists .
Objective This meta- analysis sought to systemically review and quantitatively synthesize evidence on prebiotic , probiotic , and synbiotic therapies for patients with NAFLD in r and omized controlled trials .