title: Hepatocellular carcinoma risk in HBeAg-negative chronic hepatitis B patients with or without cirrhosis treated with entecavir: HepNet.Greece cohort.
abstract: Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients treated with lamivudine. Whether HCC rates are comparable in patients treated with the current first-line antivirals remains uncertain. We estimated the incidence and evaluated predictors of HCC in a large nationwide prospective cohort (HepNet.Greece) of HBeAg-negative CHB patients treated with entecavir. HBeAg-negative CHB patients from the same cohort who were initially treated with lamivudine were used as controls. We included 321 patients treated with entecavir for a median of 40 months and 818 patients treated initially with lamivudine for a median of 60 months. In the entecavir group, HCC developed in 4 of 321 (1.2%) patients at a median of 1.5 (range: 1.0-4.5) years, while the cumulative HCC incidence was significantly higher in cirrhotics than noncirrhotics (1, 3, 5 years: 0%, 3%, 9% vs 1%, 1%, 1%; P = 0.024) and in older patients (P = 0.026). Entecavir compared with lamivudine group patients had lower HCC incidence (1, 3, 5 years: 0.3%, 1.2%, 2.8% vs 0.7%, 3.8%, 5.6%; P = 0.024). However, in multivariable Cox regression analysis, the HCC risk was independently associated with older age (P < 0.001), male gender (P = 0.011) and cirrhosis (P = 0.025), but not with the initial agent. In conclusion, our large nationwide study indicates that the HCC risk remains increased in entecavir-treated HBeAg-negative CHB patients with cirrhosis, particularly of older age, at least for the first 5 years. The HCC risk does not seem to be significantly reduced with entecavir compared with antiviral therapy starting with lamivudine.
authors.affiliation: Gastroenterology Department, Athens University Medical School, Laikon General Hospital of Athens, Athens, Attica, Greece.
authors.forename: G V
authors.initials: GV
authors.lastname: Papatheodoridis
authors.forename: S
authors.initials: S
authors.lastname: Manolakopoulos
authors.forename: G
authors.initials: G
authors.lastname: Touloumi
authors.forename: G
authors.initials: G
authors.lastname: Nikolopoulou
authors.forename: M
authors.initials: M
authors.lastname: Raptopoulou-Gigi
authors.forename: C
authors.initials: C
authors.lastname: Gogos
authors.forename: I
authors.initials: I
authors.lastname: Vafiadis-Zouboulis
authors.forename: D
authors.initials: D
authors.lastname: Karamanolis
authors.forename: A
authors.initials: A
authors.lastname: Chouta
authors.forename: A
authors.initials: A
authors.lastname: Ilias
authors.forename: C
authors.initials: C
authors.lastname: Drakoulis
authors.forename: K
authors.initials: K
authors.lastname: Mimidis
authors.forename: I
authors.initials: I
authors.lastname: Ketikoglou
authors.forename: E
authors.initials: E
authors.lastname: Manesis
authors.forename: M
authors.initials: M
authors.lastname: Mela
authors.forename: G
authors.initials: G
authors.lastname: Hatzis
authors.forename: G N
authors.initials: GN
authors.lastname: Dalekos
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D006115:Greece / Q000453:epidemiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine
keywords: cirrhosis; entecavir; hepatitis B; hepatocellular carcinoma; lamivudine