title: Safety of long-term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection.
abstract: European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long-term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti-HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1× upper normal limit at least once during follow-up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered.
  
  
  CONCLUSIONS
  Among patients with a prHBV infection and rheumatologic indications for long-term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost-effective in this clinical setting.
authors.affiliation: Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.affiliation: Rheumatology Unit, Medical School, University of Bari, Bari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Notarnicola
authors.affiliation: Rheumatology Unit, Medical School, University of Bari, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lopalco
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Viggiani
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sebastiani
authors.affiliation: Rheumatology Unit, Medical School, University of Bari, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Covelli
authors.affiliation: Rheumatology Unit, Medical School, University of Bari, Bari, Italy.
authors.forename: Florenzo
authors.initials: F
authors.lastname: Iannone
authors.affiliation: Department of Surgery-Transplantation Service, Catholic University of Rome, Rome, Italy.
authors.forename: Alfonso W
authors.initials: AW
authors.lastname: Avolio
authors.affiliation: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: Rheumatology Unit, Department Research Center of Systemic Autoimmune and Autoinflammatory Diseases, University of Siena, Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
authors.affiliation: Rheumatology Unit, Medical School, University of Bari, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lapadula
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D001168:Arthritis / Q000097:blood / Q000188:drug therapy*; D001691:Biological Therapy / Q000009:adverse effects*; D005260:Female; D006509:Hepatitis B / Q000139:chemically induced*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D000069283:Rituximab; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000637:Transaminases