title: Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma.
abstract: BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded.
  
  
  RESULTS
  HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003).
  
  
  CONCLUSIONS
  Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.
authors.affiliation: Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: Pellicelli
authors.affiliation: Instituto Superiore Sanità Rome, Italy.
authors.forename: Pascal
authors.initials: P
authors.lastname: Vignally
authors.affiliation: Infectious Disease Ospedale Sant'Anna e San Sebastiano Caserta, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Messina
authors.affiliation: Infectious Disease Ospedale D. Cotugno Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Izzi
authors.affiliation: Liver Unit Policlinico Casilino Rome, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Mazzoni
authors.affiliation: Liver Unit ASL/RMA Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Barlattani
authors.affiliation: Liver Unit Ospedale di Casarano Rome, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Bacca
authors.affiliation: Liver unit Ospedale S. Pertini Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
authors.affiliation: Liver Unit Ospedale Santo Spirito Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mecenate
authors.affiliation: Infectious and Tropical Disease Policlinico Umberto I Rome, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Stroffolini
authors.affiliation: Infectious and Tropical Disease Policlinico Umberto I Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Furlan
authors.affiliation: Liver Unit University "Campus Biomedico" Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Picardi
authors.affiliation: Liver Unit University "Campus Biomedico" Rome, Italy.
authors.forename: Umberto V
authors.initials: UV
authors.lastname: Gentilucci
authors.affiliation: Infectious Disease IRCCS San Matteo Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gulminetti
authors.affiliation: Infectious Disease Ospedale San Camillo de Lellis Rieti, Italy.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Bonaventura
authors.affiliation: Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Villani
authors.affiliation: Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: D'Ambrosio
authors.affiliation: Infectious Disease Policlinico Umberto I Rome, Italy.
authors.forename: Amerigo
authors.initials: A
authors.lastname: Paffetti
authors.affiliation: Infectious Disease Policlinico Umberto I Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mastropietro
authors.affiliation: Liver Unit Azienda Ospedaliera Sant'Andrea, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Marignani
authors.affiliation: Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Fondacaro
authors.affiliation: Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cerasari
authors.affiliation: Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Andreoli
authors.affiliation: Infectious Disease IRCCS San Matteo Pavia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Barbarini
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D000077712:Telbivudine; D000068698:Tenofovir; D013936:Thymidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine; C106812:adefovir dipivoxil; D013936:Thymidine