AntiHBc Testing

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Anti-HBc Testing

• National Liaison Committee
• July 8, 2002

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Objectives

• to educate the NLC on the biology of Hepatitis B
  (HBV)
• to present options for an additional test for
  screening donors for HBV (anti-HBc testing)
• to discuss the factors to consider for each option

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Hepatitis B Detection in Donated Blood

• current test is for the detection of the virus,
  i.e. Hepatitis B surface antigen (HBsAg)
• anti-HBc tests for the antibody to the Hepatitis
  B core antigen

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Anti-HBc Testing

• not for the detection of early infections, i.e.
  does not shorten the window period
• detects chronic carriers whose HBsAg level is too
  low to be detected with current tests

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Frequency of Transfusion Transmitted HBV (TT-HBV)
Potentially Eliminated by Anti-HBc Testing

• British study 1999 1/50,000 units
• USA study 2001 1/50,000 units
• confidence intervals for both studies
• 1/12,800 - 1/333,333 units
• both used HBsAg tests that are less sensitive
  than tests used in Canada

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Anti-HBc Testing vs NAT to Prevent TT-HBV

• unlikely to be decreased with minipool NAT
• may be slightly decreased with single unit NAT

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Approximate Residual Risks for Transfusion
Transmitted HIV and HCV

• HIV - 1/2,500,000
• HCV - 1/500,000

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Severity of HBV Infection

• immunocompentent adults
• lt 5 develop chronic infection (with the
  potential for liver failure, carcinoma)
• chronicity much higher if infected in neonatal
  period (up to 90)
• fulminant infection occurs but is rare
• unknown for immunosuppressed persons but likely
  poorer outcomes
• immunization programs targeting children and
  adolescents are increasing

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Estimated Potential Benefits of anti-HBc Testing
at CBS per year (800,000 units)
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Testing Options for Anti-HBc

• A number of testing options are possible - each
  has its advantages disadvantages.

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Factors to Consider for Each Option

• decrease in HBV transmission
• donor loss
• potential effects on manufactured plasma
  derivatives (issue resolved)
• logistics
• cost

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Options for anti-HBc Testing

• test first donations relapsed donors, defer if
  anti-HBc positive (one time)
• rationale - most chronic infections occur in
  persons infected at a young age so would increase
  ratio true vs false positives
• test all donations, defer if anti-HBc positive
  (all)

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Options for Anti-HBc Testing

• test all donations, defer only on second anti-HBc
  positive donation (repeat)
• would decrease number of donors deferred for
  false positive results
• test all donations, defer only if anti-HBc
  positive and anti-HBs negative (re-entry)
• would decrease the deferral of non-infectious,
  naturally immunized donors

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Safety - Decrease in HBV Transmission

• all/repeat - maximum impact
• one time - less than all/repeat
• re-entry - same (or slightly less??) than
  all/repeat

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Causes of Donor Loss

• infectious units
• true positive, naturally immunized,
  non-infectious donors (anti-HBs positive)
• false positives

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Rate of anti-HBc Positivity in American Red
Cross Donors

• first time donors - 1.3
• repeat donors - 0.2
• weighted first time/repeat donors (22/78) -
  0.43

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Donations and Donor Loss - Years 1 and 2 (n
740,000)
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Costs Associated withDonor Loss

• costs of recruiting new donors
• irritation/bewilderment of non-infectious
  anti-HBc positive donors, particularly repeat
  donors

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Laboratory Costs

• testing personnel and reagents in 11 labs
• assuming repeat reactive rate of 1.4
• does not include SOP development and
  implementation
• does not include IT support
• does not include replacement of lost donors

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Laboratory Costs

• one time testing
• year 1 - 1,360,000
• subsequent years - 650,000
• testing all donations
• 2,100,000 per year

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Cost of anti-HBc Testing on PRISM

• approximately 2.03 per test

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Anti-HBc -- Risk Management Analysis

• a risk management strategy should be implemented
  to reduce the risk of HBV transmission
• however, ideally, this risk should be assessed
  and prioritized relative to other risks that CBS
  faces
• re-entry algorithm preferable (good balance
  between optimizing safety and minimizing
  unnecessary donor loss)
• prepare now to implement re-entry option in order
  to be able to start as soon as the conversion to
  MAK occurs

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Anti-HBc Testing in Other Countries

• USA -- repeat testing, since early 1980s
• Japan -- do test, use re-entry algorithms
• UK - do not test, under discussion
• rest of Europe -- variable
• France, Germany -- all
• Sweden -- one time

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Hema-Quebecs Position

• Board of Directors mandated H-Q to pursue
  anti-HBc testing
• met with Health Canada (HC) in September 2001, to
  explore anti-HBc testing using a re-entry
  algorithm - HC opposed to this strategy
• met with HC in March 2002, to explore anti-HBc
  testing using a repeat strategy - HC open to
  this strategy

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Expert Advisory Committee -- Blood Regulations
(EAC-BR)

• 2000-2001 - diverse opinions
• November 23, 2001 - A panel will be struck to
  review all scientific data and risk-benefit
  analysis
• February 13, 2002 -

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Summary

• small but real risk of TT-HBV that can be further
  decreased with currently available, fairly
  affordable technology
• donor loss at a level that could be replaced
• if CBS does not proceed we will be alone in North
  America

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EMT Proposal

• EMT has endorsed a policy to proceed with
  anti-HBc testing
• exactly how and when to implement yet to be
  determined although likely plan will be to
  implement simultaneously with MAK
• this position is supported by the Safety, Science
  Ethics Committee of the Board

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EMT Proposal (Contd)

• strategies to collect data that could eventually
  lead to Health Canada approval for re-entry of
  non-infectious donors should be developed

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Testing for Anti-HBc Next Steps

• presentation discussion at NLC (July,
  September)
• review of NLC input by SSEC
• presentation of motion by SSEC to the Board
• development of a comprehensive business case

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Testing for anti-HBc -- Additional Reading

• Kleinman SH, Busch MP. HBV amplified and back
  in the blood safety spotlight. Transfusion
  2001411081-1085.
• Kleinman SH. An analysis of possible blood donor
  anti-HBc screening scenarios. Submitted to CBS,
  September 4, 2001.
• Petraszko T. Testing for Antibody to Hepatitis B
  Core Antigen. CBS Position Paper, February 2001.