Interpretive Handbook

Immunocompetent individuals infected with hepatitis C virus (HCV) will have anti-HCV antibodies detectable in their serum. In general, 70% to 80% of these individuals will develop chronic infection with ongoing viral replication in the liver and detectable HCV RNA in serum, eventually causing fibrosis and cirrhosis. The other 20% to 30% of infected individuals recover from the infection without evidence of viral replication or the presence of detectable HCV RNA.

In patients with chronic HCV infection, the response to combined interferon-alpha and ribavirin therapy is correlated with pretreatment serum HCV RNA levels (viral load) and HCV genotype. Similarly, the optimal duration of combined interferon and ribavirin therapy can be determined from the patient's pretreatment viral load and HCV genotype. Clinical studies also indicate that a decrease in HCV RNA levels of more than 2 log  IU/mL at 4 weeks and/or 12 weeks of therapy is predictive of an increased chance of achieving a sustained virologic response (undetectable HCV RNA levels in serum 6 months after completing antiviral therapy). Despite typically undergoing a longer duration of treatment (48 weeks versus 24 weeks), patients with chronic infection due to HCV genotypes 1 and 4 generally have less favorable sustained virologic response rates (40%-60%) than those infected with genotypes 2 and 3 (>80%). To determine the duration of treatment and monitor the response to anti-HCV therapy, HCV RNA levels in serum are typically measured in patients at 0 (baseline) 4 weeks (rapid virologic response, RVR), 8 weeks, 12 weeks (early virologic response: EVR), end-of-treatment (24, 28, or 48 weeks depending on HCV genotype and treatment response), and 24 weeks post-treatment (sustained virologic response: SVR).

The following algorithms are available in Special Instructions:
-Testing Algorithm for the Diagnosis of Hepatitis C
-Chronic Hepatitis C Standard-of-Care Treatment Algorithm: Combined Pegylated Interferon and Ribavirin Therapy
-Chronic Hepatitis C Treatment Algorithm: HCV Genotype 1 with Telaprevir-containing Combination Therapy

-Chronic Hepatitis C Treatment and Monitoring Algorithm: Boceprevir-Containing Combination Therapy (HCV Genotype 1 only)

Detection of acute hepatitis C virus (HCV) infection (ie, <2 months from exposure) 

Detection and confirmation of chronic HCV infection 

Quantification of HCV RNA in serum of patients with chronic HCV infection (previously anti-HCV antibody-positive) 

Monitoring disease progression in chronic HCV infection and/or response to anti-HCV therapy

This assay has a serum hepatitis C virus (HCV) RNA quantification result range from 43 to 69,000,000 IU/mL (1.63-7.84 log IU/mL).

An "Undetected" result indicates that HCV RNA was not detected in the specimen. A titer result indicates the presence of HCV infection with active viral replication.

A "Detected" result with the comment "HCV RNA level is <43 IU/mL (<1.63 log IU/mL). This assay cannot accurately quantify HCV RNA below this level" indicates that the HCV RNA level is below the lower limit of quantification for this assay. When clinically indicated, follow-up testing by this assay is recommended in 1 to 2 months. For the purposes of assessing response-guided therapy eligibility, an "Undetected" result is required; a "Detected" result below the limit of quantification should not be considered equivalent to an "Undetected" result.

A "Quantitative" result expressed in IU/mL and log IU/mL indicates the degree of active HCV viral replication in the patient. Monitoring HCV RNA levels over time can be important for assessing disease progression or monitoring a patient's response to anti-HCV therapy.

A "Detected" result with the comment "HCV RNA level is >69,000,000 IU/mL (>7.84 log IU/mL). This assay cannot accurately quantify HCV RNA above this level" indicates that the HCV RNA level is above the upper limit of quantification for this assay.

An "Indeterminate" result with the comment "Inconclusive result. Submit a new specimen for testing if clinically indicated" indicates that inhibitory substances may be present in the specimen. When clinically indicated, collection and testing of a new specimen is recommended.

This test is not licensed by the FDA as a screening test for hepatitis C virus (HCV) infections or a diagnostic test to confirm the presence of HCV infection.

Except for immunocompromised patients or patients with suspected acute hepatitis, laboratory evaluation of HCV infection status should begin with HCV serologic testing, including testing for the presence of anti-HCV antibodies (see Recommended Approach to the Diagnosis, Monitoring, and Treatment of Patients with Hepatitis C Virus in Special Instructions). A diagnosis of chronic HCV infection should not be based solely on the presence of detectable or quantifiable HCV RNA in a single serum specimen.

An "Undetected" HCV RNA test result in conjunction with a positive anti-HCV antibody status (assay signal-to-cutoff ratio of > or =3.8 by EIA, or > or =8.0 by chemiluminescence immunoassay: CIA]) does not exclude the possibility of a resolved HCV infection. When clinically indicated, to distinguish between past/resolved HCV infection and chronic HCV infection with episodic viral replication, patients should be retested for HCV RNA in 1 to 2 months.

The presence of anti-HCV antibodies (assay signal-to-cutoff ratio of <3.8 by EIA or <8.0 by CIA) in patients without detectable HCV RNA may be confirmed by RIBA/80181 Hepatitis C Virus Antibody Confirmation by Recombinant Immunoblot Assay (RIBA), Serum.

Quantitative HCV RNA results generated by this assay may be more than 0.5 log IU/mL lower than those of the VERSANT HCV RNA 3.0 Assay (bDNA) among some clinical serum specimens. Patient care providers are encouraged to use the same HCV RNA quantification assay for serial monitoring of HCV RNA levels in individual patients.

According to the manufacturer, HCV RNA levels from some patients with HCV genotype 4 may be underquantified with this assay by up to 1.0 to 1.5 log IU/mL in comparison to other methods. An internal study has confirmed this observation (see Supportive Data).

Undetected

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