Interpretation of Test Results

The presence of HCV RNA in serum or plasma defines active infection, and HCV RNA is usually detectable within the first week after exposure. However, a single negative HCV RNA test result does not exclude the possibility of active infection because viremia may be intermittent in some chronically infected patients. An HCV RNA test may be the only evidence of infection in individuals with false-negative antibody tests. False-negative HCV antibody tests can occur in HIV-1 infected individuals, patients undergoing hemodialysis, and patients with HCV-associated essential mixed cryoglobulinemia.91-93

In addition to HCV diagnosis, qualitative HCV RNA tests are used to assess virological response to therapy. A negative HCV RNA test at the completion of therapy defines an end-of-treatment response (ETR), and a negative test 6 months after the completion of therapy defines a sustained virological response (SVR).

HCV RNA quantitation is useful in planning duration of therapy and in predicting the likelihood of response to treatment. Patients with high HCV RNA levels tend to respond less well to IFN and ribavirin, but lengthening the course of therapy from 24 to 48 weeks more than doubles the response rate. Patients with viral loads greater than 800,000 IU/ml are considered to have high HCV RNA levels. HCV viral load does not predict disease progression, is not correlated with disease severity, and, consequently, should not be routinely monitored in untreated patients.

Viral load testing can be used in an early assessment of viral kinetics in patients undergoing treatment with IFN and ribavirin. Patients who fail to achieve at least a 2 log10 decline in viral load after 12 weeks of treatment have little chance of an SVR and therapy should be discontinued.

Viral genotyping, like viral load, helps predict the outcome of therapy and determine its duration. Currently, the only clinically relevant distinction for patients undergoing therapy is between genotype 1 and other genotypes. Patients with a genotype 1 infection require higher doses of ribavirin and treatment for 48 weeks rather than 24 weeks to increase the likelihood of an SVR. There is no proven association between genotype and disease progression or severity, so genotyping should be reserved for those patients being considered for treatment. Routine determination of HCV subtypes (e.g., 1a or 1b), other than for epi-demiological purposes, is not warranted.

In summary, a qualitative HCV test is used for the initial evaluation of HCV antibody-positive individuals to distinguish active from resolved infections. Before initiating treatment,HCV viral load and genotype tests are performed to determine the dosing and length of treatment. After 12 weeks of treatment, the HCV viral load is measured to confirm at least a 2 log10 decline in viral load, which will be used to decide whether to continue or terminate treatment. At the end of either 24 or 48 weeks of treatment, a negative qualitative HCV test defines an ETR, and a negative qualitative test 6 months after the end of treatment defines an SVR. Assays with a limit of detection of <50 IU/ml should be used to define ETR and SVR to avoid misclassifying therapeutic outcomes. For patients not achieving an SVR, there is little experience with retreatment.

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