title: Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population.
  
  
  METHODS
  We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network.
  
  
  RESULTS
  A total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82-212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (p<0.001). HCC incidence was higher in older patients (p<0.001) and patients with lower baseline platelet counts (p=0.02). Twelve patients who developed HCC achieved virologic response (HBV DNA <80 IU/mL) before HCC. At baseline, higher CU-HCC and GAG-HCC, but not REACH-B scores were associated with development of HCC. Discriminatory performance of HCC risk scores was low, with sensitivity ranging from 18% to 73%, and c-statistics from 0.71 to 0.85. Performance was further reduced in Caucasians with c-statistics from 0.54 to 0.74. Predicted risk of HCC based on risk-scores declined during ETV therapy (all p<0.001), but predictive performances after 1 year were comparable to those at baseline.
  
  
  CONCLUSIONS
  Cumulative incidence of HCC is low in patients treated with ETV, but ETV does not eliminate the risk of HCC. Discriminatory performance of HCC risk scores was limited, particularly in Caucasians, at baseline and during therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Arends
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Sonneveld
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Roeland
authors.initials: R
authors.lastname: Zoutendijk
authors.affiliation: Department of Hepatology and Gastroenterology, Kings College London, London, UK.
authors.forename: Ivana
authors.initials: I
authors.lastname: Carey
authors.affiliation: Department of Hepatology and Gastroenterology, Imperial College London, London, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.affiliation: Infectious Diseases, Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.affiliation: NIHR Biomedical Research Unit, Centre for Liver Research, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Mutimer
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jurriën G P
authors.initials: JG
authors.lastname: Reijnders
authors.affiliation: NIHR Biomedical Research Unit, Centre for Liver Research, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Ye
authors.initials: Y
authors.lastname: Oo
authors.affiliation: Ifi Institute, Asklepios Klinik St. Georg, Hamburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Department of Gastroenterology and Rheumatology, Hepatology Section, University Clinic Leipzig, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: van Bömmel
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.affiliation: Infectious Diseases, Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.affiliation: Department of Gastroenterology and Rheumatology, Hepatology Section, University Clinic Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Welzel
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Hepatology, Hospital Vall de Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: Department of Hepatology, Hôpital de la Croix-Rousse Hospices Civils de Lyon, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pradat
authors.affiliation: Department of Hepatology, Hôpital de la Croix-Rousse Hospices Civils de Lyon, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents; D006528:Carcinoma, Hepatocellular / Q000208:ethnology* / Q000209:etiology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000208:ethnology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D044465:White People
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C413685:entecavir; D006147:Guanine
keywords: ANTIVIRAL THERAPY; HEPATITIS B; HEPATOCELLULAR CARCINOMA