Clinical Significance

Hepatitis C virus (HCV) is recognized as the cause of most cases of posttransfusion hepatitis and is a significant cause of morbidity and mortality worldwide. In the United States, HCV infection is quite common, with an estimated 2.4 million chronic HCV carriers.

Laboratory testing for HCV infection usually begins by screening for the presence of HCV antibodies in serum, using an FDA-approved screening test. Specimens that are repeatedly reactive by screening tests should be confirmed with HCV tests with higher specificity, such as direct detection of HCV RNA by reverse transcription-PCR (RT-PCR) or HCV-specific antibody confirmatory tests.

HCV antibodies are usually not detectable during the first 2 months following infection, but they are usually detectable by the late convalescent stage (>6 months after onset) of infection. These antibodies do not neutralize the virus and they do not provide immunity against this viral infection. Decrease in the HCV antibody level in serum may occur after resolution of infection.

Current screening serologic tests to detect antibodies to HCV include EIA and chemiluminescence immunoassay. Despite the value of serologic tests to screen for HCV infection, several limitations of serologic testing exist:

• There may be a long delay (up to 6 months) between exposure to the virus and the development of a detectable HCV antibody
• False-reactive screening test result can occur
• A reactive screening test result does not distinguish between past (resolved) and present HCV infection
• Serologic tests cannot provide information on clinical response to anti-HCV therapy

Reactive screening test results should be followed by a supplemental or confirmatory test, such as nucleic acid test for HCV RNA or HCV antibody confirmatory test. Nucleic acid tests provide a very sensitive and specific approach for the direct detection of HCV RNA.