***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 Morbid obese patients have a high rate of nonalcoholic fatty liver disease ( NAFLD ) and nonalcoholic steatohepatitis ( NASH ) . NASH is related to the progression and poor evolution of chronic hepatopathy in NAFLD , so that its detection makes it possible to identify the subjects who are most at risk in order to prioritize treatment . The ELF test ( Enhanced Liver Fibrosis test ; Siemens Diagnostics , NY , USA ) has been assessed for its capacity to detect fibrosis in patients with NAFLD , but its capacity for diagnosing NASH has not been checked . Aims Our objective is to determine the utility of the ELF test for detecting NASH in morbid obese patients with suspected NAFLD . Methods ELF values were determined in a cohort of obese patients who underwent bariatric surgery with suspected NAFLD .  Liver biopsy was used as the reference st and ard . Results The values of ELF were significantly higher in patients with NASH ( p = 0.002 ) and in those who presented with metabolic syndrome ( p = 0.047 ) . An ELF cut-off point of 8.72 allows the detection of patients with NASH with a sensitivity of 71.4 % and a specificity of 74.1 % ( AUC = 0.742 , p = 0.002 ) . Conclusions The ELF test is efficient for the identification of obese patients with NAFLD and early signs of steatohepatitis and fibrosis Background Liver fibrosis is the main determinant and predictor of the clinical course of nonalcoholic fatty liver disease ( NAFLD ) . To date , a liver biopsy is still considered the gold st and ard for staging fibrosis . The aim of this study was to investigate the diagnostic accuracy of the commercial enhanced liver fibrosis ( ELF ) test manufacturer 's cutoff value ( ≥9.8 ) in identifying severe fibrosis for adult patients with histologically confirmed NAFLD . Methods We tested the ELF test in a clinical practice , prospect i ve cohort of 82 consecutive patients who consecutively underwent percutaneous liver biopsy .  Results All stages of liver fibrosis were represented in our cohort , and severe fibrosis was present in 15 of 82 patients ( 18.3 % ) . The stage of fibrosis was significantly associated with ELF score ( Spearman 's rho = 0.483 , p<0.001 ) . The commercial ELF test manufacturer 's cutoff identified severe fibrosis with good sensitivity ( 86.7 % ; 95 % confidence interval [ 95 % CI ] , 0.69 - 1.04 ) and high specificity ( 92.5 % ; 95 % CI , 0.86 - 0.99 ) , with a positive predictive value of 72 % and negative predictive value of 97 % . Conclusions Our data could support the use of the ELF test in clinical practice BACKGROUND & AIMS Histologic examination of a liver biopsy specimen is regarded as the reference st and ard for detecting liver fibrosis . Biopsy can be painful and hazardous , and assessment is subjective and prone to sampling error . We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis . METHODS In an international multicenter cohort study , serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease . Discriminant analysis of a test set of sample s was used to identify an algorithm combining age , hyaluronic acid , amino-terminal propeptide of type III collagen , and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum sample s. RESULTS The algorithm detected fibrosis ( sensitivity , 90 % ) and accurately detected the absence of fibrosis ( negative predictive value for significant fibrosis , 92 % ; area under the curve of a receiver operating characteristic plot , .804 ; st and ard error , .02 ; P < .0001 ; 95 % confidence interval , .758-.851 ) . Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease . The algorithm performed equally well in comparison with each of the pathologists . In contrast , pathologists ' agreement over histologic scores ranged from very good to moderate ( kappa = .97-.46 ) . CONCLUSIONS Assessment of liver fibrosis with multiple serum markers used in combination is sensitive , specific , and reproducible , suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases Background and Aims Liver stiffness measurement ( LSM ) and FibroTest ( FT ) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy . However , to date , diagnostic performances of Enhanced Liver Fibrosis ( ELF ) test , which consists of hyaluronic acid , aminoterminal propeptide of procollagen type-III , and tissue inhibitor of matrix metalloproteinases-1 , have not been compared to those of LSM and FT in Asian chronic hepatitis B ( CHB ) patients . Methods Between June 2010 and November 2011 , we prospect ively enrolled 170 CHB patients who underwent liver biopsies along with LSM , FT , and ELF .  The Batts system was used to assess fibrosis stages . Results Areas under receiver operating characteristic curves ( AUROCs ) to predict significant fibrosis ( F≥2 ) , advanced fibrosis ( F≥3 ) , and cirrhosis ( F = 4 ) were 0.901 , 0.860 , and 0.862 for ELF , respectively ; 0.937 , 0.956 , and 0.963 for LSM ; and 0.896 , 0.921 , and 0.881 for FT . AUROCs to predict F≥2 were similar between each other , whereas LSM and FT had better AUROCs than ELF for predicting F≥3 ( both p<0.05 ) , and LSM predicted F4 more accurately than ELF ( p<0.05 ) . Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5 , 9.4 , and 10.1 for F≥2 , F≥3 , and F = 4 , respectively . Using suggested ELF , LSM and FT cutoffs to diagnose F1 , F2 , F3 , and F4 , 91 ( 53.5 % ) , 117 ( 68.8 % ) , and 110 ( 64.7 % ) patients , respectively , were correctly classified according to histological results . Conclusions ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients , especially in predicting F≥2 . However , LSM consistently provided better performance for predicting F≥3 and F4 Background and Aim Detection of advanced fibrosis ( F3-F4 ) in nonalcoholic fatty liver disease ( NAFLD ) is important for ascertaining prognosis . Serum markers have been proposed as alternatives to biopsy . We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms . Methods We included 158 patients with biopsy-proven NAFLD . Of these , 38 had advanced fibrosis . The following fibrosis algorithms were calculated : NAFLD fibrosis score , BARD , NIKEI , NASH-CRN regression score , APRI , FIB-4 , King´s score , GUCI , Lok index , Forns score , and ELF . Study population was r and omly divided in a training and a validation group . A multiple logistic regression analysis using bootstrapping methods was applied to the training group . Among many variables analyzed age , fasting glucose , hyaluronic acid and AST were included , and a model ( LINKI-1 ) for predicting advanced fibrosis was created . Moreover , these variables were combined with platelet count in a mathematical way exaggerating the opposing effects , and alternative models ( LINKI-2 ) were also created . Models were compared using area under the receiver operator characteristic curves ( AUROC ) . Results Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83 , respectively . Higher accuracy was achieved with the novel LINKI algorithms . AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89 . Conclusion The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be vali date d in further studies including larger cohorts BACKGROUND & AIMS In nonalcoholic fatty liver disease ( NAFLD ) , the distinction between steatosis and steatohepatitis ( NASH ) and the assessment of the severity of the disease rely on liver histology alone . The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH . METHODS Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 sample s collected . The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test . RESULTS No features displayed high agreement ; substantial agreement was only seen for steatosis grade ; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis ; fair agreement for Mallory bodies ; acidophilic bodies and lobular inflammation displayed only slight agreement . Overall , the discordance rate for the presence of hepatocyte ballooning was 18 % , and ballooning would have been missed in 24 % of patients had only 1 biopsy been performed . The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74 . Discordance of 1 stage or more was 41 % . Six of 17 patients with bridging fibrosis ( 35 % ) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy . Intraobserver variability was systematic ally lower than sampling variability and therefore could not account for most of the sampling error . CONCLUSIONS Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma ; therefore , sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies The main aim of this study was the comparative evaluation of nonalcoholic fatty liver disease (  NAFLD ) fibrosis score ( NFS ) , fibrosis 4 index ( FIB-4 ) , AST-to-Platelet Ratio Index ( APRI ) , and enhanced liver fibrosis ( ELF ) test in distinguishing none/early ( F0/F1 ) from significant/advanced ( F2/F3 ) fibrosis in NAFLD patients , thereby providing an external validation cohort . Thirty-one patients with biopsy-proven NAFLD and 10 matched controls without NAFLD were prospect ively enrolled . Serum hyaluronic acid ( HA ) , aminoterminal propeptide of type III procollagen ( PIIINP ) , tissue inhibitor of metallo-proteinases (TIMP)-1 , and biochemical tests were measured . NFS , FIB-4 , APRI , and ELF were calculated . ELF , FIB-4 , and APRI , but not NFS , were higher in F2/F3 than F0/F1 group . Specifically , ELF [ area under the ROC curve ( AUROC ) : 0.86±0.10 ; p=0.004 ) and APRI ( AUROC : 0.86±0.07 ; p=0.005 ] , but not NFS ( AUROC : 0.68±0.12 ; p=0.16 ) , and FIB-4 ( AUROC : 0.71±0.11 ; p=0.10 ) , could similarly discriminate F0/F1 from F2/F3 stage . The sensitivity , specificity , positive predicted value ( PPV ) , and negative predicted value ( NPV ) were : a ) for cut-off of APRI=0.5 , 85.7 % , 70.8 % , 46.2 % , and 94.4 % , respectively , and b ) for cut-off of ELF=9.0 , 85.7 % , 83.3 % , 60.0 % , and 95.2 % , respectively . When ln(PIIINP ) or TIMP-1 were combined with APRI , the combined AUROCs could distinguish F2/F3 from F0/F1 , but without significantly higher accuracy compared with APRI alone . APRI could also distinguish patients with simple steatosis from nonalcoholic steatohepatitis , and those with from those without lobular inflammation and ballooning , findings warranting further research . In conclusions : The application of ELF test and APRI can distinguish F0/F1 from F2/F3 fibrosis stages in NAFLD patients BACKGROUND & AIMS The development of non-invasive liver fibrosis tests may enable earlier identification of patients with non-alcoholic fatty liver disease ( NAFLD ) requiring referral to secondary care . We developed and evaluated a pathway for the management of patients with NAFLD , aim ed at improving the detection of cases of advanced fibrosis and cirrhosis , and avoiding unnecessary referrals . METHODS This was a prospect i ve longitudinal cohort study , with analyses performed before and after introduction of the pathway , and comparisons made to unexposed controls . We used a 2-step algorithm combining the use of Fibrosis-4 score followed by the ELF ™ test if required . RESULTS In total , 3 
    Output:
    
The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cutoffs .