title: Are current screening protocols for chronic hepatitis B virus infection adequate?
abstract: Chronic hepatitis B virus (HBV) infection screening usually includes only HBV surface antigen (HBsAg) testing; HBV core and surface antibody (anti-HBc, anti-HBs) assays, indicating resolved infection and immunity, are not routinely performed. Yet, serum HBV DNA is measurable in approximately 10% of HBsAg-negative/anti-HBc-positive cases, representing occult HBV infection (OBI). Patient blood samples from 2 Veterans Affairs medical center look-back investigations were screened for HBV infection using HBsAg enzyme immunoassays. Supplementary testing included anti-HBc and anti-HBs enzyme immunoassays. For anti-HBc-positive samples, HBV DNA testing was performed. Background OBI prevalence was further estimated at these 2 facilities based on HBV serology testing results from 1999-2012. Finally, a literature review was performed to determine OBI prevalence in the published literature. Of 1887 HBsAg-negative cohort patients, 98 (5.2%) were anti-HBc positive/anti-HBs negative; and 175 (9.3%), anti-HBc positive/anti-HBs positive. Six of 273 were HBV DNA positive, representing 0.3% of the total tested and 2.2% who were anti-HBc positive/anti-HBs negative or anti-HBc positive/anti-HBs positive. Among 32,229 general population veterans at these 2 sites who had any HBV testing, 4/108 (3.7%) were HBV DNA positive, none of whom were part of the cohort. In 129 publications with HBsAg-negative patients, 1817/1,209,426 (0.15%) had OBI. However, excluding blood bank studies with greater than 1000 patients, the OBI rate increased to 1800/17,893 (10%). OBI is not rare and has implications for transmission and disease detection. HBsAg testing alone is insufficient for detecting all chronic HBV infections. These findings may impact blood donation, patient HBV screening, follow-up protocols for patients assumed to have cleared the infection, and initiation of immunosuppression in patients with distant or undetected HBV.
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA, USA; Stanford University, Stanford, CA, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Mortensen
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA, USA; Stanford University, Stanford, CA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Kamali
authors.affiliation: Office of Public Health, Department of Veterans Affairs, Washington, DC, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Schirmer
authors.affiliation: Office of Public Health, Department of Veterans Affairs, Washington, DC, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lucero-Obusan
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Winston
authors.affiliation: Office of Public Health, Department of Veterans Affairs, Washington, DC, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Oda
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA, USA; Stanford University, Stanford, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Winters
authors.affiliation: Office of Public Health, Department of Veterans Affairs, Washington, DC, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Durfee
authors.affiliation: Office of Public Health, Department of Veterans Affairs, Washington, DC, USA; Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Martinello
authors.affiliation: Office of Public Health, Department of Veterans Affairs, Washington, DC, USA.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Davey
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA, USA; Stanford University, Stanford, CA, USA; Office of Public Health, Department of Veterans Affairs, Washington, DC, USA. Electronic address: mark.holodniy@va.gov.
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
mesh_terms: D004279:DNA, Viral / Q000097:blood; D003955:Diagnostic Tests, Routine / Q000379:methods*; D006302:Health Services Research; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000175:diagnosis*; D008403:Mass Screening / Q000379:methods*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens
keywords: Epidemiology; Hepatitis B virus (HBV); Review; Serology; Veterans