title: Development of Serum Marker Models to Increase Diagnostic Accuracy of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: The New LINKI Algorithm Compared with Established Algorithms.
abstract: OBJECTIVE
  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 randomly 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.
  
  
  CONCLUSIONS
  The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Byron
authors.initials: B
authors.lastname: Lykiardopoulos
authors.affiliation: Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hannes
authors.initials: H
authors.lastname: Hagström
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Simone
authors.initials: S
authors.lastname: Ignatova
authors.affiliation: Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Stål
authors.affiliation: Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hultcrantz
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Ekstedt
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Stergios
authors.identifier: http://orcid.org/0000-0001-7614-739X
authors.initials: S
authors.lastname: Kechagias
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000465:Algorithms; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase