title: Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir.
abstract: OBJECTIVE
  The risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB), treated with entecavir (ETV) or tenofovir (TDF), is unclear. We evaluated the incidence and predictors of HCC and the accuracy of existing HCC risk scores in Caucasian CHB patients receiving ETV/TDF.
  
  
  METHODS
  This large, multicentre, retrospective cohort study included 1666 adult Caucasian CHB patients under ETV/TDF for 39 months. CHB without cirrhosis, compensated and decompensated cirrhosis were present in 67%, 39%, and 3% of patients, respectively. The predictability of baseline parameters and three risk scores (GAG-HCC, CU-HCC, and REACH-B), developed in Asian patients, was assessed.
  
  
  RESULTS
  The cumulative probability of HCC was 1.3%, 3.4%, and 8.7% at year-1, year-3, and year-5 after ETV/TDF onset. Older age and lower platelets were strong independent HCC predictors in the total population and in the subgroups of cirrhotic and non-cirrhotic patients, while liver disease severity was an independent HCC predictor in the total population and in the cirrhotics. GAG-HCC, CU-HCC, and REACH-B risk scores were associated with HCC development only in the univariable but not in the multivariable analyses and offered poor to modest predictability.
  
  
  CONCLUSIONS
  HCC can still develop in Caucasian CHB patients treated with ETV/TDF. Besides the well-known predictors of HCC, such as older age, male gender and more advanced liver disease, lower platelets represent an independent factor of higher HCC risk. The applicability and predictability of HCC risk scores developed in Asian patients are poor or modest in Caucasian CHB patients, for whom different risk scores are required.
authors.affiliation: Academic Department of Gastroenterology, Laiko General Hospital, Athens University Medical School, Athens, Greece; 2nd Department of Internal Medicine, Athens University Medical School, Hippokratio Hospital of Athens, Athens, Greece. Electronic address: gepapath@med.uoa.gr.
authors.forename: George V
authors.initials: GV
authors.lastname: Papatheodoridis
authors.affiliation: Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa, Greece.
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
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: Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Goulis
authors.affiliation: Department of Gastroenterology & Hepatology, ErasmusMC, Rotterdam, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Arends
authors.affiliation: Department of Hygiene, Epidemiology & Medical Statistics, Athens University Medical School, Athens, Greece.
authors.forename: Vana
authors.initials: V
authors.lastname: Sypsa
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokratio Hospital of Athens, Athens, Greece.
authors.forename: Spilios
authors.initials: S
authors.lastname: Manolakopoulos
authors.affiliation: Division of Gastroenterology, 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 Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, 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: Keskın
authors.affiliation: Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
authors.forename: Savvoula
authors.initials: S
authors.lastname: Savvidou
authors.affiliation: Department of Gastroenterology & Hepatology, ErasmusMC, Rotterdam, The Netherlands.
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokratio Hospital of Athens, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Papaioannou
authors.affiliation: Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, 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, 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, The 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, 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: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000208:ethnology* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006115:Greece / Q000453:epidemiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000208:ethnology; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000208:ethnology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D000068698:Tenofovir; D013997:Time Factors; D014421:Turkey / Q000453:epidemiology; D044465:White People
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine
keywords: CU-HCC; Cirrhosis; Entecavir; GAG-HCC; Hepatitis B; Hepatocellular carcinoma; REACH-B; Risk scores; Tenofovir