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

PLoS One. 2016 Dec 9;11(12):e0167776. doi: 10.1371/journal.pone.0167776. eCollection 2016.

Abstract

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 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.

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Algorithms
  • Area Under Curve
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Female
  • Humans
  • Liver / pathology*
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology*
  • Logistic Models
  • Male
  • Middle Aged
  • Models, Biological
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / complications*
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Young Adult

Substances

  • Biomarkers
  • Blood Glucose
  • Aspartate Aminotransferases
  • Alanine Transaminase

Grants and funding

This study was supported by the Royal Swedish Academy of Sciences Foundations (http://www.kva.se/en/), grant ME2015-0011 (HH), and the Medical Research Council of Southeast Sweden (http://www.fou.nu/is/forss), grant F2004-303 (SK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.