***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: BACKGROUND / AIMS Non-Alcoholic Steatohepatitis ( NASH ) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus ( T2DM ) . Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH , but also leads to weight gain . To underst and the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat ( WBF ) and total body water ( TBW ) .  METHODS Twenty-one patients received pioglitazone and 14 placebo in a double-blind , r and omized fashion for a period of 6 months . WBF and TBW were measured before and after treatment using DXA , a water dilution technique and bioimpedance . RESULTS Pioglitazone increased body weight ( from 93.6+/-4.2 to 96.1+/-4.5 kg , p<0.003 ) and WBF measured with DXA ( from 32.9+/-2.1 to 35.4+/-2.5 kg , p<0.002 ) while no changes were seen with placebo .  Total body water was not altered significantly either after pioglitazone ( from 45.4+/-2.3 to 45.6+/-2.7 l , p = NS ) or placebo . Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments . CONCLUSIONS Six months of pioglitazone  treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention BACKGROUND / AIMS Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis , antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis . Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease . METHODS This was an open-labeled , prospect i ve , r and omized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase , despite a three-month reducing diet . Patients consuming alcohol ( more than 20 g/day ) were excluded . The patients were r and omly prescribed either oral vitamin E ( 600 IU/day ) plus vitamin C ( 500 mg/day ) or ursodeoxycholic acid ( 10 mg/kg/day ) . Patients were r and omized as two groups to receive vitamin E plus vitamin C combination ( 28 patients , 10 F ) or ursodeoxycholic acid treatment ( 29 patients , 13 F ) . RESULTS There was no significant change in body mass index before and after the treatment in both groups . At the end of six months of therapy , serum aspartate aminotransferase and aminotransferase levels significantly decreased in both treatment options . Vitamin E and C combination was more efficacious on serum aminotransferase levels than ursodeoxycholic acid , but the difference was not significant . Alanine aminotransferase decreased to normal levels in 17 of 27 ( 63 % ) and in 16 of 29 patients ( 55 % ) , respectively , in the two groups . Gamma-glutamyl transpeptidase decreased in patients receiving ursodeoxycholic acid , but no change was obtained in the vitamin-treated patients . CONCLUSIONS Vitamin E plus C combination treatment is a safe , inexpensive and effective treatment option in patients with fatty liver disease , with results comparable to those obtained with ursodeoxycholic acid . Since more effective new therapeutic options are lacking , patients with fatty liver disease should be encouraged to take vitamin E and C supplements , which are safe and affordable BACKGROUND No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis , which is characterized by insulin resistance , steatosis , and necroinflammation with or without centrilobular fibrosis . Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus . METHODS We r and omly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet  ( a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight ) plus pioglitazone ( 45 mg daily ) or a hypocaloric diet plus placebo . Before and after treatment , we assessed hepatic histologic features , hepatic fat content by means of magnetic resonance spectroscopy , and glucose turnover during an oral glucose tolerance test ( [14C]glucose given with the oral glucose load and [3H]glucose given by intravenous infusion ) . RESULTS Diet plus pioglitazone , as compared with diet plus placebo , improved glycemic control and glucose tolerance ( P<0.001 ) , normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels ( by 40 % vs. 21 % , P=0.04 ) , decreased alanine aminotransferase levels ( by 58 % vs. 34 % , P<0.001 ) , decreased hepatic fat content ( by 54 % vs. 0 % , P<0.001 ) , and increased hepatic insulin sensitivity ( by 48 % vs. 14 % , P=0.008 ) . Administration of pioglitazone , as compared with placebo , was associated with improvement in histologic findings with regard to steatosis ( P=0.003 ) , ballooning necrosis ( P=0.02 ) , and inflammation ( P=0.008 ) . Subjects in the pioglitazone group had a greater reduction in necroinflammation ( 85 % vs. 38 % , P=0.001 ) , but the reduction in fibrosis did not differ significantly from that in the placebo group ( P=0.08 ) . Fatigue and mild lower-extremity edema developed in one subject who received pioglitazone ; no other adverse events were observed . CONCLUSIONS In this proof-of-concept study , the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis . Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone . ( Clinical Trials.gov number , NCT00227110 [ Clinical Trials.gov ] . ) OBJECTIVE Hepatic steatosis is a common complication in patients with lipodystrophies and can lead to cirrhosis . There is no proven effective therapy for hepatic steatosis , but cholic acid ( CA ) , a farnesoid X receptor agonist , has previously been shown to reduce hepatic triglyceride ( TG ) content in mice and serum TG in humans . Our objective was to assess clinical efficacy and tolerability of CA therapy in patients with lipodystrophy and hepatic steatosis . DESIGN A r and omized , double-blind , placebo-controlled , crossover study . METHODS Eighteen patients with genetic or autoimmune lipodystrophies and elevated hepatic TG content participated in the study . The intervention was CA ( 15 mg/kg per day ) compared with placebo for a period of 6 months each . Hepatic TG content , the primary outcome variable , was measured with (1)H magnetic resonance spectroscopy at baseline and at 3 and 6 months during each study period . Levels of serum alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , gamma-glutamyl transpeptidase ( GGT ) , and TG were secondary end points of the study . RESULTS Compared with placebo , CA did not reduce ( median ( interquartile range ) hepatic TG content ( 14.8 % ( 9.4 - 19.0 % ) vs 15.9 % ( 10.5 - 26.5 % ) respectively ; P=0.42 ) or serum TG ( ( 340 mg/dl ( 233 - 433 mg/dl ) vs 390 mg/dl ( 233 - 595 mg/dl ) respectively ; P=0.45 ) ) . CA therapy also did not change AST , ALT , or GGT levels . Two patients developed diarrhea and excessive flatus while taking CA and these symptoms resolved after reducing the dose of CA . CONCLUSION CA was well tolerated but did not reduce hepatic TG content in patients with lipodystrophy Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed BACKGROUND & AIMS Nonalcoholic steatohepatitis ( NASH ) is a leading cause of chronic liver disease for which there is limited therapy available . Insulin sensitizing , anti-inflammatory , and antifibrotic properties of thiazolidinediones support their use in treating NASH . We have evaluated pioglitazone in the treatment of nondiabetic patients with NASH . METHODS We r and omized 74 nondiabetic patients ( 45 men ; median age , 54 y ) with histologically proven NASH to 12 months of st and ard diet , exercise , and either placebo or pioglitazone ( 30 mg/day ) . Sixty-one patients ( 30 placebo , 31 pioglitazone ) had liver biopsies both at the beginning and the end of the study . RESULTS Compared with placebo , pioglitazone therapy was associated with an increase in weight ( mean change , -0.55 vs + 2.77 kg ; P = .04 ) and a reduction in glucose ( + 0.4 vs -0.1 mmol/L ; P = .02 ) , HbA1c ( + 0.16 % vs -0.18 % ; P = .006 ) , insulin C peptide level ( + 42 vs -78 pmol/L ; P = .02 ) , alanine aminotransferase level ( -10.9 vs -36.2 u/L ; P = .009 ) , gamma-glutamyltransferase level ( -9.4 vs -41.2 u/L ; P = .002 ) , and ferritin ( -11.3 vs -90.5 microg/L ; P = .01 ) . Histologic features including hepatocellular injury ( P = .005 ) , Mallory-Denk bodies ( P = .004 ) , and fibrosis ( P = .05 ) were reduced in patients treated with pioglitazone compared with those in the placebo group . CONCLUSIONS Pioglitazone therapy over a 12-month period in nondiabetic subjects with NASH result ed in improvements in metabolic and histologic parameters , most notably liver injury and fibrosis . Larger extended trials are justified to assess the long-term efficacy of pioglitazone in this patient group INTRODUCTION The burden of non-alcoholic steatohepatitis ( NASH ) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy . Pilot studies suggest that pentoxifylline ( PTX ) can reduce liver injury in patients with NASH . OBJECTIVE We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH . MATERIAL AND METHODS Thirty patients with biopsy proven NASH were r and omized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months . Metabolic parameters , aminotransferases , liver histology and hepatic gene expression changes were compared . RESULTS At baseline the groups were similar . Adverse events were mild , most frequently headache and abdominal cramps , and did not differ between groups ( p = NS ) . After 12 months , ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L ( p < 0.05 ) , respectively in patients treated with PTX . No significant effect was seen with  placebo . Steatosis 
    Output:
    
High- quality evidence supports the effect of vitamin E , TZDs , and obeticholic acid over placebo in improving ballooning degeneration .
All four interventions seemed to have at least moderate- quality evidence over placebo to improve steatosis .
Moderate- quality evidence supports that TZDs , pentoxifylline , and obeticholic acid  decrease lobular inflammation .
All the head-to-head comparisons were supported by very-low- quality evidence except for superiority of TZDs over vitamin E on improving steatosis and lobular inflammation , which had moderate- quality evidence .
Based on direct and network meta- analysis , pentoxifylline and obeticholic acid improve fibrosis , and vitamin E , TZDs , and obeticholic acid improve ballooning degeneration in patients with NASH .