title: Distribution of total DNA and cccDNA in serum and PBMCs may reflect the HBV immune status in HBsAg+ and HBsAg- patients coinfected or not with HIV or HCV.
abstract: BACKGROUND
  The potential reservoir role of serum and peripheral blood mononuclear cells (PBMCs) for total HBV DNA (tDNA) and cccDNA still remains unknown.
  
  
  METHODS
  We analyzed tDNA and cccDNA with a single sensitive and validated standardized real-time PCR method in serum and PBMCs in two populations of chronic HBV infection coinfected or not with HCV and/or HIV viruses: a retrospective cohort of 130 HBsAg-negative (HBsAg-) patients with "anti-HBc alone" or anti-HBc and anti-HBs antibodies (Ab) and a cohort of 70 HBsAg-positive patients, 16 of them being prospectively followed under treatment.
  
  
  RESULTS
  Among HBsAg- patients, HBV DNA was detected in serum or PBMCs in about half of the cases with various distributions of tDNA and cccDNA: in HIV-negative patients with an "antiHBc alone" profile, tDNA was mostly detected in PBMCs suggesting a possible active role of PBMCs; although cccDNA was not detected in PBMCs in HIV-positive patients, tDNA and cccDNA were mostly observed in serum, suggesting a specific pattern of more "persistent" than "occult" infection in this population. Patients with anti-HBc and anti-HBs Ab harbored tDNA in serum or in PBMCs, regardless of their HIV or HCV status, raising the question of a viral reactivation risk during immunosupression in these patients. Among HBsAg+ patients, tDNA was detected in serum and PBMCs of 88.5% of the cases and cccDNA in 22%. Levels of tDNA in both compartments were highly correlated during treatment, suggesting a passive reservoir role for PBMCs.
  
  
  CONCLUSIONS
  The respective distribution of tDNA and cccDNA in serum and PBMCs may reflect the different immune statuses of the host in HBsAg+ and HBsAg- patients. The frequency of HBV DNA in PBMCs from AgHBs- patients suggests a viral reactivation risk during immunodepression in those patients.
authors.affiliation: Inserm UMR 1092, Faculté de médecine, Université Limoges, 2, rue du Docteur-Marcland, 87025 Limoges cedex, France.
authors.forename: V
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.forename: A
authors.initials: A
authors.lastname: Wagner
authors.forename: P
authors.initials: P
authors.lastname: Carrier
authors.forename: V
authors.initials: V
authors.lastname: Marczuk
authors.forename: I
authors.initials: I
authors.lastname: Chemin
authors.forename: F
authors.initials: F
authors.lastname: Lunel
authors.forename: I
authors.initials: I
authors.lastname: Fouchard-Hubert
authors.forename: S Si
authors.initials: SS
authors.lastname: Ahmed
authors.forename: A
authors.initials: A
authors.lastname: Abergel
authors.forename: A
authors.initials: A
authors.lastname: Rousseau
authors.forename: A
authors.initials: A
authors.lastname: Lefebvre
authors.forename: M
authors.initials: M
authors.lastname: Debette-Gratien
authors.forename: F
authors.initials: F
authors.lastname: Denis
authors.forename: S
authors.initials: S
authors.lastname: Alain
mesh_terms: D060085:Coinfection; D004270:DNA, Circular / Q000097:blood*; D004279:DNA, Viral / Q000097:blood*; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000276:immunology*; D006509:Hepatitis B / Q000097:blood* / Q000150:complications / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear; D012189:Retrospective Studies
chemical_list: D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens