title: Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration.
abstract: OBJECTIVE
  To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.
  
  
  METHODS
  We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ(2) test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.
  
  
  RESULTS
  Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up.
  
  
  CONCLUSIONS
  While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hunt
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Beste
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Elliott
authors.initials: E
authors.lastname: Lowy
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Ayako
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Moylan
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: George N
authors.initials: GN
authors.lastname: Ioannou
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelley
authors.affiliation: Christine M Hunt, Cynthia A Moylan, Michael J Kelley, Dawn Provenzale, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States.
authors.forename: Dawn
authors.initials: D
authors.lastname: Provenzale
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D018450:Disease Progression; D057286:Electronic Health Records; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D017093:Liver Failure / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D019984:Quality Indicators, Health Care; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use*; D012698:Serologic Tests; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014493:United States Department of Veterans Affairs; D014611:Vaccination; D058014:Veterans Health; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D018937:Hepatitis C Antibodies; D000069283:Rituximab
keywords: Anti-CD20 antibody; Chemotherapy; Hepatitis B; Hepatitis B antivirals; Hepatitis B reactivation; Lymphoma; Rituximab; Vaccination; Veteran