title: HIV-induced immune deficiency is associated with a higher risk of hepatocarcinoma, ANRS CO3 Aquitaine Cohort, France, 1998-2008.
abstract: OBJECTIVE
  HIV and viral hepatitis co-infected patients are at high risk for hepatocarcinoma. The contribution of immunodeficiency is not well documented. We aimed at estimating the relationship between the occurrence of hepatocarcinoma and both types of measures of immunodeficiency, current and cumulative (time below a given threshold), to assess their independent effects.
  
  
  METHODS
  HIV-infected adults included in the ANRS CO3 Aquitaine Cohort with no history of cancer, ≥ 3 months of follow-up between 1998 and 2008, ≥ 1 CD4+ cell count (CD4+), and documented hepatitis virus status were eligible. Extended Cox proportional hazards models with delayed entry were used to estimate the risk of hepatocarcinoma. Exposure to a CD4+ < 350 or <500 cells/mm(3) (current and cumulative duration) was time-updated. Hepatitis B or C virus co-infection and gender were fixed-effect variables.
  
  
  RESULTS
  Sixteen cases of hepatocarcinoma were diagnosed among the 2864 eligible patients, the incidence rate was 0.78 case/1000 person-years (95% Confidence Interval [CI]: 0.40-1.16). Current CD4+ < 350 or < 500 was independently associated with a higher risk of hepatocarcinoma (Hazard Ratio [HR]: 5.0, CI 1.5-16.8, p = 0.009 and HR = 10.3, CI 1.3-82.8, p = 0.029, respectively). The occurrence of hepatocarcinoma was independent of the cumulative exposure to a CD4+ < 350 or < 500 (p = 0.38 or p = 0.80, respectively).
  
  
  CONCLUSIONS
  Presenting with CD4+ < 500 was associated with a higher risk of hepatocarcinoma, whereas the cumulative duration with immunodeficiency was not. These results suggest that moving CD4+ count above 500 following antiretroviral therapy initiation is associated with a decreased risk of hepatocarcinoma, regardless of the duration of HIV-induced immunodeficiency.
authors.affiliation: INSERM U 897, Bordeaux School of Public Health (ISPED), Université Bordeaux Segalen, Bordeaux, France. mathias.bruyand@isped.u-bordeaux2.fr
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruyand
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Vandenhende
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: Olivier
authors.initials: O
authors.lastname: Leleux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Geffard
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000276:immunology; D060085:Coinfection / Q000150:complications; D005260:Female; D005602:France / Q000453:epidemiology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D016174:Hepacivirus; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents