title: FibroGENE: A gene-based model for staging liver fibrosis.
abstract: OBJECTIVE
  The extent of liver fibrosis predicts long-term outcomes, and hence impacts management and therapy. We developed a non-invasive algorithm to stage fibrosis using non-parametric, machine learning methods designed for predictive modeling, and incorporated an invariant genetic marker of liver fibrosis risk.
  
  
  METHODS
  Of 4277 patients with chronic liver disease, 1992 with chronic hepatitis C (derivation cohort) were analyzed to develop the model, and subsequently validated in an independent cohort of 1242 patients. The model was assessed in cohorts with chronic hepatitis B (CHB) (n=555) and non-alcoholic fatty liver disease (NAFLD) (n=488). Model performance was compared to FIB-4 and APRI, and also to the NAFLD fibrosis score (NFS) and Forns' index, in those with NAFLD.
  
  
  RESULTS
  Significant fibrosis (⩾F2) was similar in the derivation (48.4%) and validation (47.4%) cohorts. The FibroGENE-DT yielded the area under the receiver operating characteristic curve (AUROCs) of 0.87, 0.85 and 0.804 for the prediction of fast fibrosis progression, cirrhosis and significant fibrosis risk, respectively, with comparable results in the validation cohort. The model performed well in NAFLD and CHB with AUROCs of 0.791, and 0.726, respectively. The negative predictive value to exclude cirrhosis was>0.96 in all three liver diseases. The AUROC of the FibroGENE-DT performed better than FIB-4, APRI, and NFS and Forns' index in most comparisons.
  
  
  CONCLUSIONS
  A non-invasive decision tree model can predict liver fibrosis risk and aid decision making.
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Eslam
authors.affiliation: Department of Systems and Biomedical Engineering, Faculty of Engineering, Minia University, Minia, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Hashem
authors.affiliation: Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.affiliation: Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany; Department of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Henry Lik Yuen
authors.initials: HLY
authors.lastname: Chan
authors.affiliation: NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, United Kingdom.
authors.forename: William L
authors.initials: WL
authors.lastname: Irving
authors.affiliation: Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom; Institute of Translational and Stratified Medicine, Plymouth University, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Sheridan
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Abate
authors.affiliation: School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, WA, Australia.
authors.forename: Leon A
authors.initials: LA
authors.lastname: Adams
authors.affiliation: Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, NSW, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Weltman
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.affiliation: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Olfat
authors.initials: O
authors.lastname: Shaker
authors.affiliation: Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany.
authors.forename: Janett
authors.initials: J
authors.lastname: Fischer
authors.affiliation: School of Medicine and Pharmacology, Fremantle Hospital, UWA, Fremantle, WA, Australia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Mollison
authors.affiliation: Department of Gastroenterology & Hepatology, Royal Perth Hospital, WA, Australia.
authors.forename: Wendy
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.affiliation: Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Riordan
authors.affiliation: Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Miele
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia.
authors.forename: Kebitsaone Simon
authors.initials: KS
authors.lastname: Kelaeng
authors.affiliation: Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia.
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlenstiel
authors.affiliation: Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: McLeod
authors.affiliation: Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Woolloongabba, QLD, Australia; The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Powell
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Douglas
authors.affiliation: Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
authors.affiliation: Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia. Electronic address: jacob.george@sydney.edu.au.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000328:Adult; D000465:Algorithms; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006521:Hepatitis, Chronic / Q000175:diagnosis / Q000503:physiopathology / Q000821:virology; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000503:physiopathology; D062072:Patient Acuity; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012107:Research Design; D018570:Risk Assessment / Q000379:methods; D000095022:Interferon Lambda
chemical_list: D005819:Genetic Markers; D007378:Interleukins; C579163:IFNL4 protein, human; D000095022:Interferon Lambda
keywords: Chronic hepatitis B; Chronic hepatitis C; Data mining analysis; Fibrosis; IFNL; NASH; Non-alcoholic steatohepatitis