title: Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study.
abstract: OBJECTIVE
  To evaluate the risk and predictors of hepatocellular carcinoma (HCC) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy.
  
  
  METHODS
  Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective-prospective cohort who were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy for ≥12 months.
  
  
  METHODS
  A nationwide network of liver centres.
  
  
  METHODS
  818 patients were included: 517 with chronic hepatitis B only; 160 with compensated cirrhosis; 56 with decompensated cirrhosis; 85 with unclassified disease severity.
  
  
  METHODS
  All patients were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy.
  
  
  METHODS
  Development of HCC.
  
  
  RESULTS
  During a median follow-up of 4.7 years, HCC developed in 49 (6.0%) patients. The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only (11.5% vs 3.2%, respectively; p<0.001). HCC developed in 0.7%, 6.7% and 11.7% of patients <50, 50-60 and >60 years old, respectively (p<0.001). Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis, but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only (p=0.076). In multivariate analysis, age, gender and cirrhosis were independently associated with HCC risk regardless of virological remission.
  
  
  CONCLUSIONS
  Long-term therapy with nucleos(t)ide analogue(s) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis, who should remain under HCC surveillance even during effective therapy. Older age and male gender remain independent risk factors for HCC, while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC.
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, Athens, Greece. gepapath@med.uoa.gr
authors.forename: George V
authors.initials: GV
authors.lastname: Papatheodoridis
authors.forename: Spilios
authors.initials: S
authors.lastname: Manolakopoulos
authors.forename: Giota
authors.initials: G
authors.lastname: Touloumi
authors.forename: Georgia
authors.initials: G
authors.lastname: Vourli
authors.forename: Maria
authors.initials: M
authors.lastname: Raptopoulou-Gigi
authors.forename: Irini
authors.initials: I
authors.lastname: Vafiadis-Zoumbouli
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Vasiliadis
authors.forename: Kostas
authors.initials: K
authors.lastname: Mimidis
authors.forename: Charalambos
authors.initials: C
authors.lastname: Gogos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Ketikoglou
authors.forename: Emanuel K
authors.initials: EK
authors.lastname: Manesis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006115:Greece / Q000453:epidemiology; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine