title: Systemic diseases and biotherapies: understanding, evaluating, and preventing the risk of hepatitis B reactivation.
abstract: Hepatitis B virus (HBV) reactivation can occur in chronic carriers of the HBV surface antigen (HBsAg) and constitutes a well-known complication of immunosuppressive therapy. HBV reactivation has also been reported after contact with the HBV. The increasing use of biological agents (TNFα antagonists, rituximab, abatacept, and tocilizumab) to treat systemic diseases has resulted in numerous publications about the risk of HBV reactivation. The relevant scientific societies have issued recommendations designed to prevent HBV reactivation. The main measures consist of screening for markers indicating chronic HBV infection (HBsAg) or HBV infection in the distant past (antibodies to the HBV core antigen) before initiating biological therapies, vaccinating marker-negative patients, and considering close follow-up or antiviral treatment before immunosuppressive treatment initiation or in the event of HBV reactivation. Here, we discuss the pathophysiological mechanisms underlying HBV reactivation during biological treatments, most notably in patients with occult HBV infection or markers for remote HBV infection, whose hepatocyte nuclei may contain a resistance form of HBV DNA known as covalently closed circular DNA (cccDNA). Assessment of the risk of reactivation relies on the HBV status, drugs used, and data from the literature. Finally, we discuss the various recommendations and modalities for HBV vaccination, preemptive treatment, and patient management, according to the level of risk and to the circumstances in which reactivation occurs.
authors.affiliation: Laboratoire de virologie et laboratoire HIFIH, UPRES EA 3859, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Lunel-Fabiani
authors.affiliation: Service de rhumatologie, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France. Electronic address: ChMasson@chu-angers.fr.
authors.forename: Charles
authors.initials: C
authors.lastname: Masson
authors.affiliation: Laboratoire de virologie et laboratoire HIFIH, UPRES EA 3859, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ducancelle
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D001691:Biological Therapy; D017325:Hepatitis B Vaccines / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination; D014775:Virus Activation / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D017325:Hepatitis B Vaccines; D014409:Tumor Necrosis Factor-alpha
keywords: Biotherapies; HBV DNA; HBsAg; Hepatitis B; Immunosuppressive treatment; Rheumatoid arthritis; Spondyloarthritis; Systemic disease; TNFα antagonists; Viral reactivation