***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The development of new insulin sensitizers is an unmet need for the treatment of type 2 diabetes . We investigated the effect of GFT505 , a dual peroxisome proliferator – activated receptor (PPAR)-α/δ agonist , on peripheral and hepatic insulin sensitivity . RESEARCH DESIGN AND METHODS Twenty-two abdominally obese insulin-resistant males ( homeostasis model assessment of insulin resistance > 3 ) were r and omly assigned in a r and omized crossover study to subsequent 8-week treatment periods with GFT505 ( 80 mg/day ) or placebo , followed by a two-step hyperinsulinemic-euglycemic insulin clamp with a glucose tracer to calculate endogenous glucose production ( EGP ) . The primary end point was the improvement in glucose infusion rate ( GIR ) . Gene expression analysis was performed on skeletal muscle biopsy specimens . RESULTS GFT505  improved peripheral insulin sensitivity , with a 21 % ( P = 0.048 ) increase of the GIR at the second insulin infusion period . GFT505 also enhanced hepatic insulin sensitivity , with a 44 % ( P = 0.006 ) increase of insulin suppression of EGP at the first insulin infusion period . Insulin-suppressed plasma free fatty acid concentrations were significantly reduced on GFT505 treatment ( 0.21 ± 0.07 vs. 0.27 ± 0.11 mmol/L ; P = 0.006 ) . Neither PPARα nor PPARδ target genes were induced in skeletal muscle , suggesting a liver-targeted action of GFT505 . GFT505 significantly reduced fasting plasma triglycerides ( −21 % ; P = 0.003 ) and LDL cholesterol ( −13 % ; P = 0.0006 ) , as well as liver enzyme concentrations ( γ-glutamyltranspeptidase : −30.4 % , P = 0.003 ; alanine aminotransferase : −20.5 % , P = 0.004 ) . There was no safety concern or any indication of PPARγ activation with GFT505 . CONCLUSIONS The dual PPARα/δ agonist GFT505 is a liver-targeted insulin-sensitizer that is a promising drug c and i date for the treatment of type 2 diabetes and nonalcoholic fatty liver disease BACKGROUND & AIMS The effects of bariatric surgery in patients with nonalcoholic fatty liver disease ( NASH ) are not well established . We performed a prospect i ve study to determine the biological and clinical effects of bariatric surgery in patients with NASH . METHODS From May 1994 through May 2013 , one hundred and nine morbidly obese patients with biopsy-proven NASH underwent bariatric surgery at the University Hospital of Lille , France ( the Lille Bariatric Cohort ) .  Clinical , biological , and histologic data were collected before and 1 year after surgery . RESULTS One year after surgery , NASH had disappeared from 85 % of the patients ( 95 % confidence interval [ CI ] : 75.8%-92.2 % ) . Compared with before surgery , patients had significant reductions in mean ± SD body mass index ( BMI , from 49.3 ± 8.2 to 37.4 ± 7 ) and level of alanine aminotransferase ( from 52.1 ± 25.7 IU/L to 25.1 ± 20 IU/L ) ; mean levels of γ-glutamyltransferases were reduced from 51 IU/L before surgery ( interquartile range [ IQR ] , 34 - 87 IU/L ) to 23 IU/L afterward ( IQR , 14 - 33 IU/L ) and mean insulin resistance index values were reduced from 3.6 ± 0.5 to 2.9 ± 0.5 ( P < .01 for each comparison ) . NASH disappeared from a higher proportion of patients with mild NASH before surgery ( 94 % ) than severe NASH ( 70 % ) ( P < .05 ) according to Brunt score . In histologic analysis , steatosis was detected in 60 % of the tissue before surgery ( IQR , 40%-80 % ) but only 10 % 1 year after surgery ( IQR , 2.5%-21.3 % ) ; the mean nonalcoholic fatty liver disease score was reduced from 5 ( IQR , 4 - 5 ) to 1 ( IQR , 1 - 2 ) ( each P < .001 ) . Hepatocellular ballooning was reduced in 84.2 % of sample s ( n = 69 ; 95 % CI : 74.4 - 91.3 ) and lobular inflammation in 67.1 % ( n = 55 ; 95 % CI : 55.8 - 77.1 ) . According to Metavir scores , fibrosis was reduced in 33.8 % of patients ( 95 % CI : 23.6%-45.2 % ) . Patients whose NASH persisted 1 year after surgery ( n = 12 ) had lost significantly less weight ( change in BMI , 9.1 ± 1.5 ) than those without NASH ( change in BMI , 12.3 ± 0.6 ) ( P = .005 ) . Patients who underwent laparoscopic gastric b and ing  lost less weight ( change in BMI , 6.4 ± 0.7 ) than those who underwent gastric bypass ( change in BMI , 14.0 ± 0.5 ) ( P < .0001 ) , and a higher proportion had persistent NASH ( 30.4 % vs 7.6 % of those with gastric bypass ; P = .015 ) . CONCLUSIONS Bariatric surgery induced the disappearance of NASH from nearly 85 % of patients and reduced the pathologic features of the disease after 1 year of follow-up . It could be a therapeutic option for appropriate morbidly obese patients with NASH who do not respond to lifestyle modifications . More studies are needed to determine the long-term effects of bariatric surgery in morbidly obese patients with NASH BACKGROUND & AIMS Severe obesity is implicated in development of nonalcoholic fatty liver disease ( NAFLD ) . Bariatric surgery induces weight loss and increases survival time of obese patients , but little is known about its effects on liver damage . We performed a 5-year prospect i ve study to evaluate fibrosis and nonalcoholic steatosis ( NASH ) in severely obese patients after bariatric surgery .  METHODS  Bariatric surgery was performed on 381 patients . Clinical and biological data , along with liver biopsies , were collected before and at 1 and 5 years after surgery . RESULTS Five years after surgery , levels of fibrosis increased significantly , but 95.7 % of patients maintained a fibrosis score < or= F1 . The percentage of patients with steatosis decreased from 37.4 % before surgery to 16 % , the NAFLD score from 1.97 to 1 , ballooning from 0.2 to 0.1 . Inflammation remained unchanged . The percentage of patients with probable or definite NASH decreased significantly over 5 years , from 27.4 % to 14.2 % . The kinetics of insulin resistance ( IR ) paralleled that of steatosis and ballooning ; the greatest improvements occurred within the first year and were sustained 5 years later . Steatosis and ballooning occurred more frequently in patients with a refractory IR profile . In multivariate analysis , the refractory IR profile independently predicted the persistence of steatosis and ballooning 5 years later . CONCLUSIONS Five years after bariatric surgery for severe obesity , almost all patients had low levels of NAFLD , whereas fibrosis slightly increased . Steatosis and ballooning were closely linked to IR ; long-term effects could be predicted by early improvement in IR BACKGROUND The bile acid derivative 6-ethylchenodeoxycholic acid ( obeticholic acid ) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease . We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis . METHODS We did a multicentre , double-blind , placebo-controlled , parallel group , r and omised clinical trial at medical centres in the USA in patients with non-cirrhotic , non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally ( 25 mg daily ) or placebo for 72 weeks . Patients were r and omly assigned 1:1 using a computer-generated , central ly administered procedure , stratified by clinical centre and diabetes status . The primary outcome measure was improvement in central ly scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment . A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment ( 72 weeks ) biopsies supported the decision to continue the trial ( relative change in alanine aminotransferase -24 % , 95 % CI -45 to -3 ) . A planned interim analysis of the primary outcome showed improved efficacy  of obeticholic acid ( p=0·0024 ) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients , but to continue the trial to obtain the 24-week post-treatment measures . Analyses were done by intention-to-treat . This trial was registered with Clinical Trials.gov , number NCT01265498 . FINDINGS Between March 16 , 2011 , and Dec 3 , 2012 , 141 patients were r and omly assigned to receive obeticholic acid and 142 to placebo . 50 ( 45 % ) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 ( 21 % ) of 109 such patients in the placebo group ( relative risk 1·9 , 95 % CI 1·3 to 2·8 ; p=0·0002 ) . 33 ( 23 % ) of 141 patients in the obeticholic acid developed pruritus compared with nine ( 6 % ) of 142 in the placebo group . INTERPRETATION Obeticholic acid improved the histological features of non-alcoholic steatohepatitis , but its long-term benefits and safety need further clarification . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases , Intercept Pharmaceuticals BACKGROUND Weight-loss medications are recommended as an adjunct to a comprehensive program of diet , exercise , and behavior therapy but are typically prescribed with minimal or no lifestyle modification . This practice is likely to limit therapeutic benefits . METHODS In this one-year trial , we r and omly assigned 224 obese adults to receive 15 mg of sibutramine per day alone , delivered by a primary care provider in eight visits of 10 to 15 minutes each ; lifestyle-modification counseling alone , delivered in 30 group sessions ; sibutramine plus 30 group sessions of lifestyle-modification counseling ( i.e. , combined therapy ) ; or sibutramine plus brief lifestyle-modification counseling delivered by a primary care provider in eight visits of 10 to 15 minutes each . All subjects were prescribed a diet of 1200 to 1500 kcal per day and the same exercise regimen . RESULTS At one year , subjects who received combined therapy lost a mean ( + /-SD ) of 12.1+/-9.8 kg , whereas those receiving sibutramine alone lost 5.0+/-7.4 kg , those treated by lifestyle modification alone lost 6.7+/-7.9 kg , and those receiving sibutramine plus brief therapy lost 7.5+/-8.0 kg ( P<0.001 ) . Those in the combined-therapy group who frequently recorded their food intake lost more weight than those who did so infrequently ( 18.1+/-9.8 kg vs. 7.7+/-7.5 kg , P=0.04 ) . CONCLUSIONS The combination of medication and group lifestyle modification result ed in more weight loss than either medication or lifestyle modification alone . The results underscore the importance of prescribing weight-loss medications in combination with , rather than in lieu of , lifestyle modification Objectives : To compare the long-term benefit of gastric bypass [ Roux-en-Y gastric bypass ( RYGB ) ] versus adjustable gastric b and ing ( AGB ) on  nonalcoholic fatty liver disease ( NAFLD ) in severely obese patients . Background : NAFLD improves after weight loss surgery , but no histological study has compared the effects of the various bariatric interventions . Methods : Participants consisted of 1236 obese patients ( body mass index = 48.4 ± 7.6 kg/m2 ) , enrolled in a prospect i ve longitudinal study for up to 5 years after RYGB  ( n = 681 ) or AGB  ( n = 55 
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Coe SG , Crook JE , Diehl NN , et al. An endoscopic quality improvement program improves detection of colorectal adenomas .