title: Use of tumor necrosis factor-alpha-blocking agents in hepatitis B virus-positive patients: reports of 3 cases and review of the literature.
abstract: OBJECTIVE
  To evaluate the development of hepatitis B virus (HBV) infection in patients receiving tumor necrosis factor-alpha-blocking agents (TNFBA), and to evaluate whether lamivudine (LAM) prophylaxis can reduce the risk of viral reactivation in inactive HBsAg carriers.
  
  
  METHODS
  Local experience and published reports were reviewed. Patients with HBV infection were classified as having chronic HBV hepatitis, or being inactive HBsAg carriers or occult carriers.
  
  
  RESULTS
  Three patients in our series and 24 patients in the literature were identified: 2 had active HBV-associated disease, 23 were inactive HBsAg carriers, and 2 occult carriers. When exposed to TNFBA, HBsAg-inactive carriers pretreated with LAM had lower risk of having detectable HBV-DNA (p=0.02) or viral reactivation (p=0.046) than those without LAM prophylaxis. In 3 patients who discontinued TNFBA, LAM prophylaxis was also discontinued 10-12 months thereafter without hepatitis flares. Two cases of reactivation in occult carriers (HBsAg-negative, anti-HBs+, anti-HBc+) were described in the literature.
  
  
  CONCLUSIONS
  TNFBA should be avoided in patients with active HBV replication and should be used with caution in inactive HBsAg carriers. In these patients, the risk of viral reactivation seems to be high, but it might be reduced by prophylactic LAM, which should probably be given for a long time when TNFBA are discontinued (e.g., 12 mo). Potential occult carriers might carry a low, but not negligible, risk of viral reactivation. They should therefore be monitored with particular care.
authors.affiliation: Rheumatology and Clinical Immunology Service, Infectious and Tropical Diseases Department, Spedali Civili and University of Brescia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zingarelli
authors.forename: Micol
authors.initials: M
authors.lastname: Frassi
authors.forename: Chiara
authors.initials: C
authors.lastname: Bazzani
authors.forename: Mirko
authors.initials: M
authors.lastname: Scarsi
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents; D001688:Biological Products; D002908:Chronic Disease; D000075202:Contraindications; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011292:Premedication; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014775:Virus Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D007166:Immunosuppressive Agents; D018894:Reverse Transcriptase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019259:Lamivudine