title: Hepatitis B virus reactivation in HBsAg-negative patients is associated with emergence of viral strains with mutated HBsAg and reverse transcriptase.
abstract: OBJECTIVE
  Virological factors associated with hepatitis B virus reactivation (HBV-R), following chemotherapy for cancer in hepatitis B surface antigen (HBsAg)-negative patients, are not well known.
  
  
  METHODS
  HBV strains from 16 patients presenting HBV-R following chemotherapy were studied and compared to those obtained from 51 HBV chronically-infected patients.
  
  
  RESULTS
  HBsAg variability was significantly increased within the major hydrophilic region, the a determinant and the C-terminal region. Amino acid substitutions were more frequently found in HBV-R patients as compared to controls at 17 and 11 positions within HBsAg and HBV-RT, respectively. This resulted in atypical serological testing in 56% of patients and detection of resistance mutation to nucleoside analogs in 12.5%.
  
  
  CONCLUSIONS
  HBsAg and HBV-RT mutations are frequently encountered in patients with HBV-R, resulting in atypical serological testing and emergence of HBV strains resistant to nucleos(t)ides analogs.
authors.affiliation: IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique - Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, URMITE UM63 CNRS 7278 IRD 198 INSERM U1095, Facultés de Médecine et de Pharmacie, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Colson
authors.affiliation: Service d'Hépato-Gastroentérologie Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université UMR INSERM 911. Facultés de Médecine et de Pharmacie, Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Borentain
authors.affiliation: Service d׳Onco-hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Coso
authors.affiliation: IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique - Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, URMITE UM63 CNRS 7278 IRD 198 INSERM U1095, Facultés de Médecine et de Pharmacie, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Motte
authors.affiliation: Service d׳Onco-hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Therese
authors.initials: T
authors.lastname: Aurran-Schleinitz
authors.affiliation: Service d׳Onco-hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.affiliation: Service d׳Onco-hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Stoppa
authors.affiliation: Service d׳Onco-hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.affiliation: Service d'Hépato-Gastroentérologie Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Serrero
authors.affiliation: Service d'Hépato-Gastroentérologie Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bertrand
authors.affiliation: Aix Marseille Université - Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology and Therapeutic Innovations Department, Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.affiliation: Service de Médecine Interne, Centre Hospitalier Universitaire de la Timone. Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Serratrice
authors.affiliation: Service d'Hépato-Gastroentérologie Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Portal
authors.affiliation: Service d'Hépato-Gastroentérologie Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
authors.forename: Daniele
authors.initials: D
authors.lastname: Botta-Fridlund
authors.affiliation: IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique - Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université, URMITE UM63 CNRS 7278 IRD 198 INSERM U1095, Facultés de Médecine et de Pharmacie, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
authors.affiliation: Service d'Hépato-Gastroentérologie Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France; Aix-Marseille Université UMR INSERM 911. Facultés de Médecine et de Pharmacie, Marseille, France. Electronic address: rene.gerolami@ap-hm.fr.
authors.forename: René
authors.initials: R
authors.lastname: Gerolami
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D014775:Virus Activation
chemical_list: D000970:Antineoplastic Agents; D006514:Hepatitis B Surface Antigens; D050505:Mutant Proteins; D012194:RNA-Directed DNA Polymerase
keywords: Chemotherapy; HBV therapy; HBV-DNA detection; HBsAg; Hepatitis B virus reactivation