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Hepatitis C virus: Prevention, screening, and interpretation of assays

Cleveland Clinic Journal of Medicine. 2010 September;77(9):616-626 | 10.3949/ccjm.77a.09162
September 1, 2010|Cleveland Clinic Journal of Medicine
Mazen Albeldawi, MD;Ernesto Ruiz-Rodriguez, MD;William D. Carey, MD
Author and Disclosure Information

Mazen Albeldawi, MD
Department of Internal Medicine, Cleveland Clinic

Ernesto Ruiz-Rodriguez, MD
Department of Internal Medicine, Cleveland Clinic

William D. Carey, MD
Transplant Center and Digestive Disease Institute, Cleveland Clinic; Director, Center for Continuing Education; Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University

Address: William D. Carey, MD, Department of Gastroenterology and Hepatology, A51, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail careyw@ccf.org

ABSTRACTPatients at risk of hepatitis C virus (HCV) infection should be screened for it so that they can be treated and potentially cured, or can at least avoid transmitting the disease to others. The authors describe why and how to screen for HCV and how to interpret the test results.

KEY POINTS

  • Patients who should be screened include intravenous drug abusers, people infected with human immunodeficiency virus, patients with unexplained elevated alanine aminotransferase levels, infants born to infected mothers, and people with infected sexual partners.
  • Patients at risk of HCV infection should be tested for anti-HCV antibody using an enzyme immunoassay (EIA).
  • Positive results on anti-HCV EIA testing should be confirmed with an assay for HCV RNA.
  • HCV genotyping can help predict the response to therapy. Genotypes 2 or 3 are more likely to respond to therapy than genotype 1.

GROUPS AT LOW RISK OF HCV

People who have had sexual relations with multiple or infected partners

Sexual activity is associated with a low but measurable risk of transmission of HCV. Large population-based studies, including the National Hepatitis Surveillance Program,25 found an independent association between HCV infection and having sexual relations with multiple partners or with a partner who is infected with HCV.

The CDC reported that 15% to 20% of patients with acute hepatitis C had a history of sexual exposure but no other risk factors. Two-thirds of them had an anti-HCV-positive sexual partner, and one-third reported having had more than two partners in the 6 months before illness.5

More data are needed to determine the risk of and the factors related to transmission of HCV between long-term steady partners as well as in persons with high-risk sexual practices, including whether other sexually transmitted diseases promote transmission of HCV by influencing viral load or modifying mucosal barriers.

Health care workers exposed to HCV, eg, by needlestick

The prevalence of HCV infection in health care workers is no greater than that in the general population, averaging 1% to 2%, and is actually 10 times lower than that of hepatitis B virus infection.47,48,61,62

However, within the disciplines, some groups have a higher prevalence of HCV infection, suggesting that some occupations carry a higher risk. In two US studies, the prevalence of HCV infection was higher in oral surgeons (2.0% and 9.3%) than in other dentists (0.7% and 0.97%).63,64

In a single study that evaluated risk factors for infection, a history of needlestick injury was the only occupational risk factor that was independently associated with HCV infection.65 The average incidence of anti-HCV seroconversion after a needlestick or after an injury with a sharp object contaminated by an HCV-positive source is 1.8% (range 0%–7%).66–69

Although no studies of incidence have documented transmission via mucous membrane or nonintact skin exposures, transmission of HCV from blood splashes to the conjunctiva have been described.70,71

Refer to Table 2 for postexposure follow-up recommendations.

It is worth noting that exposure to blood from unclean needles used in tattooing or body piercing also confers a risk of HCV infection.

SEROLOGIC SCREENING TESTS FOR HCV

Figure 2.
Figure 2 is an algorithm for laboratory investigation of suspected HCV infection,72 Table 3 summarizes how to interpret the test results, and Table 4 lists how the various tests are used in diagnosing HCV infection, estimating the prognosis, and treating HCV infection.73

Two classes of assays are used to diagnose HCV infection:

  • Serologic assays that detect specific antibody to HCV (anti-HCV)
  • Molecular assays that detect viral RNA.

Initial serologic screening tests for anti-HCV

Enzyme immunoassays (EIAs) are reproducible, inexpensive, and approved by the US Food and Drug Administration for diagnosing HCV infection. They are suitable for screening populations at risk and are recommended as the initial serologic test for patients with clinical liver disease.

Two EIAs are approved for clinical use:

  • Abbott HCV EIA 2.0 (Abbott Laboratories, Abbott Park, IL)
  • Ortho HCV Version 3.0 enzyme-linked immunosorbent assay (ELISA) (Ortho-Clinical Diagnostics, Rochester, NY).

One enhanced chemiluminescence immunoassay is also approved:

  • Vitros Anti-HCV assay (Ortho-Clinical Diagnostics). In practical terms, this test is equivalent to the two EIAs, and the discussion below about EIAs applies to this test as well.

These third-generation tests are highly sensitive (> 99%) and specific (99%) in immunocompetent patients, and eliminate the need for a confirmatory immunoblot assay in patients with clinical liver disease, particularly those with risk factors for HCV infection.

False-positive results are rare now, but they were common with earlier generations of these assays. Most false-positive results occur in patients with autoimmune liver disease or hypergammaglobulinemia who have normal liver enzyme levels and no risk factors for HCV infection. In fact, all positive anti-HCV results should be followed up with an HCV RNA test.

False-negative results are also uncommon, usually occurring only in immunosuppressed patients (eg, organ transplant recipients and HIV-positive patients) and in patients on long-term hemodialysis. Therefore, patients with a history of hemodialysis should be considered for an HCV RNA assay rather than an EIA. Measurement of ALT will not be useful because ALT levels are lower in patients with end-stage renal disease. In most other clinical situations, the HCV EIA is an outstanding screening test for HCV infection because of its high sensitivity and relatively low cost (< $50).

Although the specificity of these tests is good, the predictive value of a positive result varies substantially by the pretest probability of HCV infection. For example, in a group of injection-drug users who are very likely to have ongoing or remote infection, all positive HCV EIA results are likely truly positive.74 On the other hand, in healthy blood donors, up to half of all positive third-generation EIA tests are falsely positive.75

Important points

  • A positive anti-HCV antibody test does not distinguish acute from chronic disease or active from past infection, nor is it a sign of immunity or protection.
  • A positive anti-HCV EIA requires HCV RNA measurement to discriminate between current infection on the one hand, and either resolved HCV infection or a false-positive result on the other.
  • A positive EIA anti-HCV test is a marker that hepatitis C may be present, and it must be followed by confirmatory HCV RNA testing.
  • Physicians should be mindful of the potential tribulations associated with false-positive tests. A false-positive test may result in harm to patients that is difficult to measure, such as anxiety, labeling in the medical record, and detrimental effects on close relationships.

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