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Hepatitis C Test Recommendations

An estimated 3.5 million persons living in the United States are infected with hepatitis C virus (HCV) and approximately 50% are unaware they are infected. HCV is primarily transmitted through percutaneous exposure to infected blood. Other modes of transmission include mother-to-infant and contaminated devices shared for noninjection drug use. Sexual transmission also occurs but generally seems inefficient except among HIV-infected men who have unprotected sex with men. Injection drug use poses the most significant risk for HCV infection, accounting for at least 60% of acute HCV infections in the United States. 

CDC established risk-based HCV testing guidelines in 1998. These guidelines were expanded in 2012 with a recommendation to offer a one-time HCV testing to all persons born from 1945 through 1965 without prior ascertainment of HCV risk factors.  Both CDC and the USPSTF recommend a one-time HCV test in asymptomatic persons belonging to the 1945 through 1965 birth cohort, as well as other individuals based on exposures, behaviors, and conditions or circumstances that increase HCV infection risk.

Other persons should be screened for HCV infection risk factors. One-time testing should be performed for all persons with behaviors, exposures, and conditions or circumstances associated with an increased risk of HCV infection.

Risk Behaviors

  • Injection-drug use (current or ever, including those who injected only once) 
  • Intranasal illicit drug use

Risk Exposures

  • Persons on long-term hemodialysis (ever) 
  • Persons with percutaneous/parenteral exposures in an unregulated setting 
  • Healthcare, emergency medical, and public safety workers after needle-stick, sharps, or mucosal exposures to HCV-infected blood 
  • Children born to HCV-infected women 
  • Prior recipients of transfusions or organ transplants, including persons who: 
    • Were notified that they received blood from a donor who later tested positive for HCV 
    • Received a transfusion of blood or blood components, or underwent an organ transplant before July 1992 
    • Received clotting factor concentrates produced before 1987 
  • Persons who were ever incarcerated

Other Conditions and Circumstances

  • HIV infection 
  • Sexually-active persons about to start pre-exposure prophylaxis (PreP) for HIV 
  • Unexplained chronic liver disease and/or chronic hepatitis, including elevated alanine aminotransferase (ALT) levels 
  • Solid organ donors (deceased and living) 

All persons recommended for HCV screening should initially be tested for HCV antibody using an FDA approved immunoassay. FDA-approved tests include laboratory-based assays and a point-of-care assay (OraQuick HCV Rapid Antibody Test). A positive test result for HCV antibody indicates either current HCV infection (acute or chronic), past infection that has resolved, or a false-positive result. Patients with positive HCV antibody should have HCV nucleic acid test to distinguish between these possibilities. 

For patients with no apparent risk for HCV infection, the likelihood of a false-positive HCV-antibody test is directly related to the HCV prevalence in the tested population. False-positive HCV-antibody tests most commonly occur in populations with a low prevalence of HCV infection. For an immunocompetent population with HCV prevalence of <10%, the chance of a false positive antibody test ranges from 15-60%. False positive tests are seen most often in the elderly, dialysis patients, patients with autoimmune disease and following immunizations. 

If further testing is desired to distinguish between a true positive vs biologic false positivity for HCV antibody, repeat testing may be done with a different FDA-approved, HCV-antibody assay. A biologic false result should not occur with two different assays. An alternative strategy is to go directly to HCV RNA polymerase chain reaction. 

Persons who have a positive HCV-antibody test and negative results for HCV RNA PCR should be informed that they do not have laboratory evidence of current HCV infection. Additional HCV testing is typically unnecessary. The HCV-RNA test can be repeated when there is a high index of suspicion for recent infection or in patients with ongoing HCV infection risk. 

Patients with a positive HCV antibody and positive HCV RNA tests have active infection and should be referred for treatment. 

Circumstances associated with a false-negative EIA include patients with acute HCV infection, persons with major immunosuppression (advanced HIV infection or organ transplantation recipients), and persons with chronic renal failure on long-term hemodialysis. These patients may require HCV RNA PCR for diagnosis.  

The first enzyme immunoassay (EIA), which detected antibody to a single viral antigen, was introduced in 1989.  A more sensitive second generation EIA, was introduced in 1992, which detects antibody to several viral antigens. Today, laboratories usethird-generation immunoassays that detect antibodies that bind to recombinant antigens derived from four viral regions: core, nonstructural 3, nonstructural 4, and nonstructural 5. 

The third generation immunoassay has sensitivity of 98% and specificity of 99%.  HCV window period is typically 6 to 9 weeks from time a person is infected until HCV antibody becomes detectable.  

Specimen requirement is one SST tube of blood. PCR & genotype testing can usually be performed on the residual serum sample used for the HCV antibody test.  


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