Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease

Hepatology. 2014 Aug;60(2):565-75. doi: 10.1002/hep.27173. Epub 2014 Jun 26.


Biopsy is still the gold standard for the diagnosis of nonalcoholic steatohepatitis but the definition may vary among pathologists, a drawback especially in evaluation of biopsies for clinical trials. We previously developed a scoring system (steatosis, activity, fibrosis [SAF]) allowing the use of an algorithm (fatty liver inhibition of progression [FLIP]) for the classification of liver injury in morbid obesity. The aim of this study was to determine whether the use of the SAF score and FLIP algorithm can decrease interobserver variations among pathologists. In a first session, pathologists categorized 40 liver biopsies of patients with nonalcoholic fatty liver disease (NAFLD) according to their own experience. In a second reading session, each pathologist reclassified the same slides by using the FLIP algorithm and SAF score, blinded to their first evaluation. The experiment was repeated with two different groups of pathologists at varying levels of training in liver pathology. The percentage of biopsy interpretation concordant with reference evaluation increased from 77% to 97% in Group 1 and from 42% to 75% in Group 2 after the use of the SAF score and FLIP algorithm. The strength of concordance in classification increased in Group 1 from moderate (κ = 0.54) to substantial (κ = 0.66) and from fair (κ = 0.35) to substantial (κ = 0.61) in Group 2 with application of the algorithm. With regard to the SAF score, concordance was substantial in Group 1 for steatosis (κ = 0.61), activity (κ = 0.75), and almost perfect for fibrosis (κ = 0.83 after pooling 1a, 1b, and 1c together into a single score F1). Similar trends were observed in Group 2 (κ = 0.54 for S, κ = 0.68 for A, and κ = 0.72 for F).

Conclusion: The FLIP algorithm based on the SAF score should decrease interobserver variations among pathologists and are likely to be implemented in pathology practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms*
  • Biopsy / statistics & numerical data
  • Disease Progression
  • Fatty Liver / classification
  • Fatty Liver / pathology*
  • Female
  • Humans
  • Liver / pathology*
  • Liver Cirrhosis / classification
  • Liver Cirrhosis / pathology*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Observer Variation
  • Severity of Illness Index*