Guidelines for Laboratory Testing and Result Reporting for Antibody to Hepatitis C Virus

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Guidelines for Laboratory Testing and Result
Reporting for Antibody to Hepatitis C Virus
BPAC September 18, 2003

• Miriam J. Alter, Ph.D.
• Division of Viral Hepatitis
• Centers for Disease Control and Prevention

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Guidelines Development

• Other collaborators
• Blood collection establishments
• Manufacturers

• Working group
• Federal agencies
• CDC, FDA (CDRH, CBER)
• Professional associations
• APHL
• ASCP
• CAP
• NACB
• AACC
• ACLA
• Other experts
• University and VA hospital laboratories

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These Guidelines Are NOT Intended

• For screening or notification of blood, plasma or
  other donors, as provided for under FDA guidance
  or regulations
• To change manufacturers labeling for performing a
  specific test
• To dictate medical practice, i.e., what tests
  physicians are able to order

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Testing for Anti-HCV

• Recommended for initially identifying persons
  with HCV infection
• Antibody screening assay followed by more
  specific assay for screening-test-positives
• As is done for HBsAg and anti-HIV
• Verifying presence of anti-HCV
• Minimizes unnecessary medical visits and
  psychological harm for persons who test falsely
  positive
• Ensures counseling, medical referral and
  evaluation targeted for persons serologically
  confirmed as having been HCV infected

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Performance of Screening Tests

• Positive Predictive Value (PPV)
• Probability that a person with a positive test is
  a true positive
• Varies depending on prevalence of infection in
  population being screened

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How Anti-HCV Test Results Are Used

• Clinical diagnosis of etiology of liver disease
• Postexposure management
• Screening asymptomatic persons
• Most being tested for the first time
• Risk for infection highly variable
• High-risk (e.g., injection drug users)
• Low-risk (e.g., health-care workers)
• Lower-risk (e.g., worried well)
• Public health surveillance
• Monitor incidence and prevalence to target and
  evaluate prevention efforts

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Testing Practices

• In 1998, CDC published recommendations that all
  screening-test positives undergo more specific
  testing
• Broad educational programs targeted to physicians
  and other health care providers
• Little impact on test ordering practices
• Substantial variation among laboratories in
  routine testing algorithms
• Many report screening test positive results only
• Those that confirm use different methods (RIBA,
  NAT)
• Without additional information, may not be able
  to determine true antibody or HCV infection
  status

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Anti-HCV Testing Practices of State and
Territorial Public Health and VA Medical Center
Laboratories, 2002
Testing Practices Public health VAMC
Tests offered n43 n67 Screening
test 65 100 RIBA 38
21 Qualitative NAT 29 75 Quantitative
NAT 13 98 Supplemental testing
performed n29 n67 All screening-test-positiv
e results 35 22 Low-positive screening-test
results 10 3 Only by physician
request 17 75 None offered 38 0
Signal to cut-off ratio below a specified value
Source Werner B, APHL, 2002 Dufour R, VA, 2002
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Purpose of Laboratory Guidelines

• Adoption of standard algorithm by all
  laboratories that perform in vitro diagnostic
  testing
• Ensure results reflect true antibody status
• Independent of clinical information or origin of
  sample
• Educate
• Importance of more specific testing
• Accurate interpretation of screening and
  supplemental results
• When more specific testing should be performed
• Which tests to use
• Eliminate cost as barrier to more specific
  testing

Not intended for screening or notification of
donors
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Options for More Specific Testing When Anti-HCV
Test Requested

• Perform more specific testing on all
  screening-test positives or
• Use screening test positive signal to cutoff
  ratios to determine need for more specific
  testing
• Cutoff performs the same regardless of the
  population being tested

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Evaluation of Anti-HCV S/CO Ratios

• Screening tests
• Ortho 3.0 enzyme immunoassay (EIA) (n25,532)
• Abbott 2.0 EIA (N8,754)
• Ortho VITROS enhanced chemiluminescent assay
  (CIA) (n1326)
• More specific testing of screening-test positives
• RIBA 3.0
• NAT (Amplicor, Procleix, Nested RT-PCR)

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Study Groups for Evaluating EIA and CIA S/Co
Ratios by Prevalence of HCV Infection
1187
2066
6606
gt9000
388
6340
Number tested
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Proportion of Anti-HCV RR EIA Results Testing
RIBA Positive by S/CO Ratio
_
(N18)
(N21)
(N231)
(N765)
EIA S/CO Ratio
Source MMWR 200352(No. RR-3)1-15.
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Proportion of Anti-HCV EIA Screening-Test
Positives Testing RIBA or NAT Positive by Average
S/Co Ratio
_
EIA 2.0 or EIA 3.0
Source MMWR 200352(No. RR-3)1-15.
14
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Proportion of Anti-HCV CIA Screening Test
Positives Testing RIBA Positive by S/Co Ratio
Prevalence
gt
VITROS Anti-HCV assay
Source MMWR 200352(No. RR-3)1-15
15
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Proportion of Anti-HCV Screening Test Positives
Requiring RIBA Based on Low S/Co Ratiosby HCV
Prevalence
Source MMWR 200352(No. RR-3)1-15
16
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Using Screening Test Positive S/Co Ratio to
Determine Need For Additional Testing

• Positives with high s/co ratios can be reported
  based on screening test results alone
• gt95 will be RIBA positive
• Only positives with low s/co ratios require
  additional testing (most falsely positive)
• lt20 will confirm positive
• Limits cost while improving accuracy of reported
  results
• lt5 of high risk persons require additional
  testing

Applies only to HCV EIA 2.0, HCV version 3.0
ELISA, and VITROS Anti-HCV
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Implementation

• Determine reflex testing option to be used
• Revise SOP
• Algorithm chosen
• Procedure for reporting results
• Provide interpretation of results with report
• Educate staff and customers
• Modify requisition form

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Implications

• Patients and physicians can reliably interpret
  results
• Further clinical evaluation limited to true
  positives
• Limit unnecessary medical visits and
  psychological stress on patients who test falsely
  positive
• Substantially improve ability to establish public
  health surveillance systems to monitor effect of
  prevention and intervention activities

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Interpretation of HCV Test Results
Screening RIBA for NAT for Anti-HCV HCV
Infection Test Anti-HCV HCV RNA Status Status
Not done Not done Unknown Unknown
- NA - None
Not done Past/current
/ not done Current