title: PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy.
abstract: OBJECTIVE
  Risk scores for hepatocellular carcinoma (HCC) developed in Asians offer poor-moderate predictability in Caucasian patients with chronic hepatitis B (CHB). This nine center cohort study aimed to develop and validate an accurate HCC risk score in Caucasian CHB patients treated with the current oral antivirals, entecavir/tenofovir.
  
  
  METHODS
  We included 1815 adult Caucasians with CHB and no HCC at baseline who received entecavir/tenofovir for ⩾12 months. Using data from eight centers (derivation dataset, n=1325), a HCC risk score was developed based on multivariable Cox models and points system for simplification. Harrell's c-index was used as discrimination, bootstrap for internal validation and the data from the 9(th) and largest center (validation dataset, n=490) for external validation.
  
  
  RESULTS
  The 5-year cumulative HCC incidence rates were 5.7% and 8.4% in the derivation and validation dataset, respectively. In the derivation dataset, age, gender, platelets and cirrhosis were independently associated with HCC. The PAGE-B score was developed based on age, gender and platelets (c-index=0.82, 0.81 after bootstrap validation). The addition of cirrhosis did not substantially improve the discrimination (c-index=0.84). The predictability of PAGE-B score was similar (c-index=0.82) in the validation dataset. Patients with PAGE-B ⩽9, 10-17, ⩾18 had 5-year cumulative HCC incidence rates of 0%, 3%, 17% in the derivation and 0%, 4%, 16% in the validation dataset.
  
  
  CONCLUSIONS
  PAGE-B, which is based only on baseline patients' age, gender and platelets, represents a simple and reliable score for prediction of the 5-year HCC risk in Caucasian CHB patients under entecavir/tenofovir.
authors.affiliation: Department of Gastroenterology, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece; 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: gepapath@med.uoa.gr.
authors.forename: George
authors.initials: G
authors.lastname: Papatheodoridis
authors.affiliation: Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dalekos
authors.affiliation: Department of Hygiene, Epidemiology & Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vana
authors.initials: V
authors.lastname: Sypsa
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.affiliation: Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Goulis
authors.affiliation: Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Department of Gastroenterology & Hepatology, ErasmusMC, Rotterdam, Netherlands.
authors.forename: Heng
authors.initials: H
authors.lastname: Chi
authors.affiliation: 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Spilios
authors.initials: S
authors.lastname: Manolakopoulos
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Mangia
authors.affiliation: Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Gatselis
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Keskin
authors.affiliation: 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
authors.forename: Savvoula
authors.initials: S
authors.lastname: Savvidou
authors.affiliation: Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: de la Revilla
authors.affiliation: Department of Gastroenterology & Hepatology, ErasmusMC, Rotterdam, Netherlands.
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.affiliation: Department of Gastroenterology, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vlachogiannakos
authors.affiliation: Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece.
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Galanis
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idilman
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.affiliation: Department of Gastroenterology & Hepatology, ErasmusMC, Rotterdam, Netherlands; Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D000068698:Tenofovir / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir
keywords: Entecavir; Hepatitis B; Hepatocellular carcinoma; Tenofovir