HCV Diagnosis

Features of Hepatitis C Virus InfectionFeatures of Hepatitis C Virus Infection

Incubation periodIncubation period Average 6-7 Average 6-7 weeksweeks

Range 2-26 Range 2-26 weeksweeks

Acute illness (jaundice)Acute illness (jaundice) Mild (Mild (<<20%)20%)

Case fatality rateCase fatality rate LowLow

Chronic infectionChronic infection 75%-85%75%-85%

Chronic hepatitisChronic hepatitis 70% (most asx)70% (most asx)

CirrhosisCirrhosis 10%-20%10%-20%

Mortality from CLDMortality from CLD 1%-5%1%-5%

Chronic Hepatitis C Factors Promoting Progression or Severity

• Increased alcohol intake

• Age > 40 years at time of infection

• HIV co-infection

• ?Other– Male gender– Other co-infections (e.g., HBV)

Serologic Pattern of Acute HCV Infection with Recovery

Symptoms +/-

Time after Exposure

Tit

eranti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4YearsMonths

HCV RNA

Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection

Symptoms +/-

Time after Exposure

Tit

eranti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4YearsMonths

HCV RNA

Estimated Incidence of Acute HCV InfectionUnited States, 1960-1999

0

20

40

60

80

100

120

140

1960 1965 1970 1975 1980 1985 1989 1995 1999

Year

New

Inf

ecti

ons

/100

,000

Decline intransfusion recipients

Decline in injection drug users

Source: Hepatology 2000;31:777-82; Hepatology 1997;26:62S-65S

Transmission of HCV

• Percutaneous – Injecting drug use– Clotting factors before viral inactivation– Transfusion, transplant from infected donor – Therapeutic (contaminated equipment,

unsafe injection practices)– Occupational (needlestick)

• Permucosal– Perinatal– Sexual

Sources of Infection forPersons with Hepatitis C

Sexual 15%

Other* 5%

Unknown 10%

Injecting drug use 60%

Transfusion 10%(before screening)

*Nosocomial; Health-care work; Perinatal

Source: Centers for Disease Control and Prevention

Posttransfusion Hepatitis C

0

5

10

15

20

25

30

1965 1970 1975 1980 1985 1990 1995 2000

Year

% o

f Rec

ipie

nts I

nfec

ted

All volunteer donors

HBsAg

Donor Screening for HIV Risk Factors

Anti-HIV

ALT/Anti-HBc

Anti-HCV

Improved HCV Tests

Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997

HCV Testing Routinely Recommended

• Ever injected illegal drugs• Received clotting factors made before 1987• Received blood/organs before July 1992 • Ever on chronic hemodialysis• Evidence of liver disease

• Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood

• Children born to HCV-positive women

Based on increased risk for infection

Based on need for exposure management

Routine HCV Testing Not Recommended(Unless Risk Factor Identified)

• Health-care, emergency medical, and public safety workers

• Pregnant women

• Household (non-sexual) contacts of HCV-positive persons

• General population

HCV Counseling

• Prevent transmission to others– Direct exposure to blood– Perinatal exposure– Sexual exposure

• Refer to support group

Preventing HCV Transmission to Others

• Do not donate blood, body organs, other tissue or semen

• Do not share items that might have blood on them– personal care (e.g., razor, toothbrush)– home therapy (e.g., needles)

• Cover cuts and sores on the skin

Avoid Direct Exposure to Blood

HCV Counseling

Mother-to-Infant Transmission of HCV

• Postexposure prophylaxis not available• No need to avoid pregnancy or breastfeeding

– Consider bottle feeding if nipples cracked/bleeding

• No need to determine mode of delivery based on HCV infection status

• Test infants born to HCV-positive women– Consider testing any children born since woman

became infected– Evaluate infected children for CLD

HCV Counseling

History of HCV Testing

• First tests licensed by the Food and Drug Administration in 1990

• Since 1990 new versions of these and other FDA- approved anti HCV tests have been used for– Clinical Diagnosis of HCV– Screening of asymptomatic persons

Testing Rationale

• Testing for HCV infection by using anti-HCV is performed for

1) Clinical diagnosis of patients with signs or symptoms of liver disease

2) Management of occupational and perinatal exposures

3) Screening asymptomatic persons to identify HCV-infected persons who should receive counseling and related to the persons tested is often lacking, and even persons with risk factors for HCV infection might be at sufficiently low enough risk for infection that there screening tests could be falsely positive (e.g. health care professionals-risk but low prevalence)

HCV Infection Testing AlgorithmHCV Infection Testing Algorithmfor Diagnosis of Asymptomatic Personsfor Diagnosis of Asymptomatic Persons

EIA for Anti-EIA for Anti-HCVHCV

Negative (non-reactive)

STOP

Positive (repeat reactive)

OR

RIBA for Anti-HCVRIBA for Anti-HCVRT-PCR for HCV

RNA

Negative

STOPAdditional Laboratory Additional Laboratory Evaluation (e.g. PCR, Evaluation (e.g. PCR,

ALT)ALT)

Negative PositiveIndeterminate

Medical Medical EvaluationEvaluation

Positive

Negative PCR, Normal ALT

Positive PCR, Abnormal ALT

Source: MMWR 1998;47 (No. RR 19)

Approved Testing Kits

• Comprised of – Two enzyme immunoassays (EIA)

• Abbot HCV EIA 2.0 • ORTHO HCV Version 3.0 ELISA

– One enhanced chemiluminescence immunoassay (CIA)

• VITROS

• All of the above immunoassays use HCV-encoded recombinant antigens

Available Supplemental Tests

• Tests include– Serologic anti-HCV assay

• Nucleic acid test (NAT)– Qualitative detection of HCV-RNA

» AMPLICOR Version 2» COBAS AMPLICOR Version 2

• Recombinant immunoblot assay (RIBA)

The Laboratory used determines the type of test performed

Interpreting Antibody to Hepatitis C Virus (anti-HCV)

Test Results

Anti-HCV -Positive

• Defined as1) Anti-HCV screening test positive*

AND

Recombinant immunoblot assay (RIBA)-positive

OR

Nucleic acid test (NAT) – positive

*Interpretation of screening immunoassasy test results based on criteria provided by the manufacturer

Anti-HCV -Positive

2) anti-HCV screening test positive, NAT- negative, RIBA- positive

– An anti-HCV positive result indicates past or current HCV infection.

• An HCV RNA-positive result indicates current (active) infection BUT the significance of a single HCV RNA-negative result is unknown; it does not differentiate intermittent viremia from resolved infection

Anti-HCV-Positive

• All anti-HCV positive persons should receive – Counseling– Undergo medical evaluating, including additional

testing for the presence of virus and liver disease• Anti-HCV testing usually does not need to be repeated

after a positive anti-HCV result has been confirmed

Anti-HCV -Negative

• Defined as:1) Anti-HCV screening test negative*

OR2) Anti-HCV screening test positive, RIBA-

negative

OR3) Anti-HCV screening test positive, NAT-

negative, RIBA-negative

*Interpretation of screening immunoassasy test results based on criteria provided by the manufacturer

Anti-HCV- Negative

• An anti-HCV person is considered uninfected

• No further evaluation or follow-up for HCV is required, unless recent infection is suspected or other evidence exists to indicate HCV infection

• Abnormal liver enzyme levels in an immuno-compromised person

• A person with no other etiology for their liver disease

Anti-HCV- Indeterminate

• Defined as:

Anti-HCV screening test positive, RIBA- indeterminate

Anti-HCV- Indeterminate

• An indeterminate anti-HCV result indicates that the HCV antibody status cannot be determined– Can indicate a false positive anti HCV

screening test result, the most likely interpretation among those at low risk for HCV infection; such persons are HCV RNA-negative

– Can occur as a transient finding in a recently infected person who is in the process of seroconversion: such persons usually are HCV RNA -positive

Anti-HCV- Indeterminate

– Can be persistent finding among persons chronically infected with HCV; such persons usually are HCV RNA -positive

• If NAT is not performed, another sample should be collected for repeat anti-HCV testing (> 1 month later)

Signal to Cutoff Ratios

• Analysis of enzyme immunoassay and chemiluminescence assay data indicates that s/co ratios can be used to predict supplemental test-positive results

• A specific s/co ratio can be identified for each test that would predict a true antibody-positive result (as defined by the results of supplemental testing) ≥95% of the time, regardless of the anti-HCV prevalence or characteristics of the population being tested.

Screening test kit name Manufacturer Assay Format

Signal-to-cut—off ratio predictive of a true

positive ≥ 95% of the time

Ortho HCV Version 3.0 ELISA Test System

OrthoEIA

(Enzyme Immunoassay)≥ 3.8

Abbott HCV EIA 2.0 AbbottEIA

(Enzyme Immunoassay)≥ 3.8

VITROS Anti-HCV OrthoCIA

(Chemiluminescennt Immunoassay)

≥ 8.0

AxSYM Anti-HCV AbbottMEIA

(Microparticle Immunoassay)≥ 10.0

Architect Anti-HCV AbbottCMIA

(Chemiluminescent Microparticle Immunoassay)

≥ 5.0

Advia Centaur HCV BayerCIA

(Chemiluminescennt Immunoassay)

≥ 11.0