Hepatitis C: An Overview

HCV Testing

Who should be tested?

Testing Routinely Recommended Based on Risk of Infection
Person who ever injected illegal drugs
Persons with selected medical conditions
- Persons who received clotting factor concentrates produced before 1987
- Persons who were ever on long-term hemodialysis
- Persons with persistently abnormal alanine aminotransferace levels (persons with chronic liver disease)
Testing Routinely Recommended Based on Risk of Infection
Prior recipients of transfusions or solid organs
- Persons who were notified that they received blood from a donor who later tested positive for HCV infection
- Persons who received a transfusion of blood or blood components before July 1992
- Persons who received an organ transplant before July 1992
Testing Routinely Recommended Based on Need for Exposure
- Health care, emergency medical, and public safety workers after needlesticks, sharps, or mucosal exposures to HCV positive blood
- Children born to HCV positive women

What do test results mean?

Initial Screening
- Used to determine exposure/detect hepatitis C antibodies.
- Example: Enzyme immunoassays (EIA)
- It takes an average of 6 to 8 weeks before antibodies can be detected.
- Within three months of infection, 97 percent of persons will have sufficient antibodies to be detected with a screening test.
Initial Screening – Negative Result
- A negative test most likely means that a person is not infected.
- False negatives are uncommon.
  - May occur if a person has been recently infected.
  - May occur in individuals who are immuno-suppressed or on long-term hemodialysis.
Initial Screening - Positive Result
- False positives are uncommon.
  - Most likely to occur in individuals at low-risk for infection.
  - May occur in individuals with autoimmune liver disease.
- A positive test, especially in a person with known risk factors, most likely means that they have been exposed to the virus.
- Screening test results can be verified with a supplemental or confirmatory test.
Confirmatory Testing
- To ensure that a positive screening test result is a true positive.
- To distinguish between a resolved and an active infection.
- They can be used alone or more than one test can be used.
Supplemental Confirmatory Assay
- Detects antibodies to HCV.
- Recombinant immunoblot assay (RIBA)
- Can be done on the same blood sample as the screening assay.
- Used to determine whether an antibody positive result is a true positive result, especially in low prevalence populations.
Virus Detection Tests
- Nucleic Acid Tests (NATs)
- Tests that determine presence of the hepatitis C virus in the blood through detection of HCV RNA.
- Detection of HCV RNA provides definitive proof that an infection exists.
- There are both qualitative and quantitative virus detection tests.
Qualitative Virus Detection Tests
- Can detect the virus as early as one or two weeks after exposure.
- Can detect the virus at lower levels than quantitative tests.
- Are the preferred test for determining active infection. (AMA guidelines)
- Examples: Reverse Transcriptase-polymerase chain reaction assays (RT-PCR) or Transcription mediated amplification (TMA)
Quantitative Virus Detection Tests
- Can quantify the actual amount of the virus or the viral load.
- Often used to monitor response to treatment.
- Examples: Reverse Transcriptase-polymerase chain reaction assays (RT-PCR), Transcription mediated amplification (TMA), or branched chain DNA assays
AMA: Testing Asymptomatic People Flowchart
S/Co Ratios
- The CDC guidelines allow for the use of screening-test-positive signal-to-cut off ratios (s/co ratios) to determine need for supplemental testing.
- Positive screening tests with high s/co ratios have been demonstrated to predict a supplemental serologic-test-positive 95 percent or greater of the time.
- These tests can be reported as HCV-antibody positive without supplemental testing.
S/Co-Ratios - MDCH Flowchart

If a person is chronically infected what other tests will they do?

Genotyping
- There are at least six different genotypes of HCV.
  - Genotype 1 - 70 to 75 percent of persons infected in the US.
  - Genotypes 2 and 3 – 10 to 15 percent of persons infected in the US.
- Genotype testing should be done on all HCV positive people considering treatment.
  - Often determines length of treatment.
  - Is also a predictor of response to treatment.
Liver Enzyme Tests
- Elevated ALT levels are an indirect measure of liver cell inflammation and damage.
- In patients with risk factors and elevated liver enzymes, HCV infection is probable.
- However, the absence of elevation does not rule out significant liver damage.
- One-third to one-half of HCV infected individuals will have a normal ALT level.
Liver Biopsy
- Most sensitive measure of disease severity.
- Used to determine stage of fibrosis.
- Can be used to help predict natural history of disease.
- Often used to determine the need for treatment.
- Can also be used to predict response to treatment.
- May not be indicted for patients with genotypes 2/3.
Quantitative Virus Detection Tests
- Genotype 1:
  - A change in viral level is used to monitor response to hepatitis C treatment.
  - Test before treatment starts
  - Test at 12 weeks