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


  • Pierre Bedossa,

    Corresponding author
    1. FLIP Pathology Consortium
    • Address reprint requests to: Pierre Bedossa, M.D., Ph.D., Department of Pathology, INSERM U773, Hôpital Beaujon, 100 Boulevard General Leclerc, 92100 Clichy, France. E-mail: pierre.bedossa@bjn.aphp.fr; fax: +33140870077.

    Search for more papers by this author
  • the FLIP Pathology Consortium

    Search for more papers by this author
    • The FLIP Pathology Consortium: Pierre Bedossa, Assistance Publique-Hôpitaux de Paris, hôpital Beaujon, University Paris-Diderot, Paris, France. Alastair D. Burt, School of Medicine, University of Adelaide, Adelaide, Australia. Annette S.H. Gouw, Dept. of Pathology & Medical Biology, University Medical Center Groningen, Groningen, The Netherlands. Carolin Lackner, Institute of Pathology, Medical University of Graz, Graz, Austria. Peter Schirmacher, Institut für Pathologie, Universitätsklinikum Heidelberg, Heidelberg, Germany. Luigi Terracciano, Institute of Pathology, University Hospital, Basel, Switzerland. D. Tiniakos, Medical School, National and Kapodistrian University of Athens, Greece and Medical School, Newcastle University, Newcastle-upon-Tyne, United Kingdom. J. Brain, Medical School, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Yvonne Bury, Royal Victoria Infirmary, Hospitals Foundation Trust, Newcastle-upon-Tyne, United Kingdom. Daniela Cabibi, University of Palermo, Palermo, Italy. Frederic Charlotte, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpétrière, Université Pierre et Marie Curie, Paris, France. Ezio David, University of Torino, Ospedale Molinette, Torino, Italy. Luisa Losi, Modena University Hospital, Modena, Italy. Matteo Montani, Institute of Pathology, University of Bern, CH-3010 Bern, Switzerland. María Jesús Pareja, Hospital Universitario de Valme, Sevilla, Spain. Dominique Wendum, Assistance publique-hôpitaux de Paris, Hôpital St Antoine Université Pierre et Marie Curie. Fritz Wrba, Medical University of Vienna, Vienna, Austria. Marianne Ziol, Assistance Publique-Hôpitaux de Paris, Hôpital jean Verdier, Université Paris 13, Bobigny, France. Vlad Ratziu, Assistance Publique Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Université Pierre et Marie Curie, Paris, France.

  • Potential conflict of interest: Nothing to report.


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. (Hepatology 2014;60:565–575)