guidelines for laboratory testing and result reporting for antibody to hepatitis c virus
DESCRIPTION
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. Working group Federal agencies CDC, FDA (CDRH, CBER) Professional associations - PowerPoint PPT PresentationTRANSCRIPT
Guidelines for Laboratory Testing and Result Reporting for Antibody to
Hepatitis C Virus
Miriam J. Alter, Ph.D.
Division of Viral Hepatitis
Centers for Disease Control and Prevention
BPAC September 18, 2003
2
Guidelines Development
Working group– Federal agencies• CDC, FDA (CDRH, CBER)
– Professional associations• APHL• ASCP• CAP• NACB• AACC• ACLA
– Other experts• University and VA hospital laboratories
Other collaborators– Blood collection
establishments– Manufacturers
3
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
4
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
5
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
Tests offered n=43 n=67
Screening test 65% 100%
RIBA 38% 21%
Qualitative NAT 29% 75%
Quantitative NAT 13% 98%
Supplemental testing performed n=29 n=67
All screening-test-positive 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
Testing Practices Public health VAMC
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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) (n=25,532)– Abbott 2.0 EIA (N=8,754)– Ortho VITROS enhanced chemiluminescent assay
(CIA) (n=1326) More specific testing of screening-test positives– RIBA 3.0– NAT (Amplicor, Procleix, Nested RT-PCR)
Study Groups for Evaluating EIA and CIA S/Co Ratios by Prevalence of HCV Infection
0 5 10 15 20 25
Percentage Anti-HCV Positive
College students
Prison HCWs
Gen Population
STD patients
Hemodialysis
Selected for Risk 1187*
2066
6606
388
6340
* Number tested
>9000
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Proportion of Anti-HCV RR EIA Results Testing RIBA Positive by S/CO Ratio
0
20
40
60
80
100
1.0-<3.0 3.0-<3.5 3.5-<3.8 >3.8
Per
cent
RIB
A P
osit
ive
Students HCWs NHANES IV STD Dialysis Hi-risk
Source: MMWR 2003;52(No. RR-3):1-15.
(N=231) (N=18) (N=21) (N=765)
EIA S/CO Ratio
_
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Proportion of Anti-HCV EIA* Screening-Test Positives Testing RIBA or NAT Positive by Average S/Co Ratio
0
20
40
60
80
100
Per
cent
RIB
A o
r N
AT
P
osit
ive
<3.8 >3.8
Screening-test-positive average s/co ratio
Source: MMWR 2003;52(No. RR-3):1-15.
* EIA 2.0 or EIA 3.0
_
Group prevalence 2% 10% 25%
RIBA positive
NAT positive
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Proportion of Anti-HCV CIA* Screening Test Positives Testing RIBA Positive by S/Co Ratio
0
20
40
60
80
100
Per
cent
RIB
A P
osit
ive
1.0-7.9 8.0
Screening-test-positive s/co ratio
2% 10% >20%
Source: MMWR 2003;52(No. RR-3):1-15
* VITROS Anti-HCV assay
Prevalence
>
15
Proportion of Anti-HCV Screening Test Positives Requiring RIBA Based on Low S/Co
Ratiosby HCV Prevalence
0
5
10
15
20
25
30
35
Per
cent
Low
S/C
o R
atio
s
1-5% 10% >20%
HCV Prevalence
EIA <3.8 CIA <8.0
Source: MMWR 2003;52(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– >95% will be RIBA positive
Only positives with low s/co ratios require additional testing (most falsely positive)– <20% will confirm positive
Limits cost while improving accuracy of reported results– <5% 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 InfectionTest Anti-HCV HCV RNA Status Status
- NA* NA - None
* Not applicable
+ - NA - None
+ + Not done + Past/current
+ +/not done + + Current
+ Not done - Unknown Unknown†
† Single negative HCV RNA result cannot determine infection status
+ + - + Past/current§
§ HCV RNA can be intermittent; repeat HCV RNA
+ Not done Not done Unknown Unknown