Hepatitis C Reference Manual

Screening for High Risk Exposures

As part of a complete medical history for all patients, it is important to obtain a history of high risk exposures associated with transmission of HCV and other blood-borne pathogens. Such a history can be used to identify asymptomatic persons who should be offered screening for HCV infection. In addition, risk reduction counseling should be offered to persons with high risk behaviors (e.g., illicit injection drug use, high risk sexual practices).

Screening Asymptomatic Individuals

Screening asymptomatic individuals for HCV infection potentially benefits them in several ways. These include the opportunity to be

• evaluated for chronic liver disease and possible treatment
• counseled on avoiding potential hepatotoxins, such as alcohol, that may increase the severity of their disease
• counseled on how to reduce their risk of transmitting HCV to others

A number of issues should be considered when selecting persons for screening. People may not change their high risk behaviors or alcohol use based on knowing their test results, and it is not known if treating asymptomatic HCV-infected individuals results in lower morbidity or longer survival. In addition, testing for HCV infection may cause considerable anxiety, as disclosure of test results to others can result in disrupted personal relationships and possible discriminatory action such as loss of employment, insurance, and educational opportunities. In order to minimize possible adverse consequences of testing, appropriate pre- and post-test counseling should be provided (see the "Prevention and Counseling" section), and the confidentiality of patient test results should be protected.

Routine anti-HCV screening is currently recommended only for persons who belong to groups with a known high prevalence of HCV infection. These groups include

• persons who ever injected illicit drugs, even those who may have only experimented a few times many years ago
• persons who received clotting factor concentrates before 1987
• persons who received a transfusion of blood or blood products before 1992
• persons who received a solid organ transplant before 1992
• persons who have ever been on chronic hemodialysis

For management of specific exposures to HCV, screening is also recommended for

• sex partners of HCV-infected persons
• infants >=12 months of age born to HCV-infected women
• health care workers after accidental percutaneous or permucosal exposure to anti-HCV positive blood

Although there are other persons at risk of HCV infection, routine screening of these persons is not recommended because the overall prevalence of infection among these persons is low or unknown. This includes persons with multiple sex partners, men who have sex with men, health care workers (other than postexposure), pregnant women, household contacts of HCV-infected persons, and persons who were tattooed or had body parts pierced.

Diagnostic Tests

Figure 1. Algorithm for Screening Asymptomatic Patients for Hepatitis C Virus Infection

Serologic assays. An enzyme immunoassay (EIA) for anti-HCV is the most appropriate test for initial screening of patients for HCV infection (Figure 1). The currently available second and third version EIAs detect anti-HCV in >=95% of infected patients. A supplemental test, such as RIBA (recombinant immunoblot assay), should be used to verify a positive anti-HCV by EIA, especially in populations with a low prevalence of infection such as blood donors. In these low risk groups, the positive predictive value of the EIA is <50%. In patients presenting with biochemical or clinical evidence of liver disease (e.g., elevated ALT levels), a positive EIA is usually sufficient to diagnose HCV infection, especially if the patient has risk factors for infection; however, the addition of the supplemental test provides greater confidence in the test result.

Nucleic acid detection. The diagnosis of HCV infection is also possible by detecting HCV RNA using reverse transcriptase PCR (RT-PCR) techniques. HCV RNA can be detected within 1 to 2 weeks after exposure to the virus, weeks before onset of ALT elevations or the appearance of anti-HCV. In some patients, the detection of HCV RNA may be the only evidence of HCV infection. Although PCR assays for HCV RNA are available from several commercial laboratories on a research-use basis, the results may vary considerably between laboratories. Both false positive and false negative results can occur from improper collection, handling, and storage of test samples. In addition, HCV RNA may be detected intermittently during the course of infection, so the meaning of a single negative PCR result is not conclusive. Because of assay variability, rigorous proficiency testing is recommended for clinical laboratories performing this assay, and results of PCR testing should be interpreted cautiously.

Quantitative assays for measuring the titer of HCV RNA have been developed, including a branched chain DNA assay (Quantiplex HCV RNA Assay [bDNA], Chiron Corp., Emeryville, California) and quantitative PCR (Amplicor HCV Monitor, Roche Molecular Systems, Branchburg, New Jersey). These quantitative assays are less sensitive compared to standard PCR assays; thus, they should not be used as a primary test to confirm or exclude the diagnosis of HCV infection, or to monitor the endpoint of treatment. To date, sequential measurement of HCV RNA levels has not proven useful in managing patients with hepatitis C.

Several different nucleic acid detection methods also have been developed to group isolates of HCV based on genotypes. The applicability of these tests in the clinical setting, however, has not been determined.

Diagnosis

Relatively few patients will seek medical care for acute hepatitis C as most patients are asymptomatic or present with mild flu-like symptoms. Of those who do have acute hepatitis C, 70% to 80% have detectable anti-HCV at clinical presentation, and 90% have anti-HCV detectible by 12 weeks after onset. Therefore, anti-HCV testing should be repeated if acute hepatitis C is suspected and initial testing is negative. Most patients with acute hepatitis C remain chronically infected, and approximately two-thirds or more of patients with chronic infection have abnormal ALT activity. Based on serial serum samples with normal values for ALT and negative results for HCV RNA, it is estimated that 15% of HCV-infected patients resolve their infection and recover from hepatitis C.

In most instances, evidence of chronic HCV infection will be discovered by chance through screening tests at the time of blood donation or routine physical examination. Most persons who are found to be positive for anti-HCV in these situations are chronically infected. No tests are available to differentiate between acute, chronic, or resolved infection, and the diagnosis of chronic hepatitis C is usually based on the presence of elevated ALT values in patients who are anti-HCV positive. For anti-HCV positive patients with a normal ALT value, the presence of ongoing liver inflammation should be assessed by monitoring serum ALT values several times over a 6 to 12 month period, because abnormalities may be present only intermittently in patients with chronic hepatitis C.

Diagnostic criteria for perinatal HCV infection have not been established. A variety of anti-HCV patterns have been observed in both infected and uninfected infants of anti-HCV positive mothers. Because passively-acquired maternal antibody may persist for some months -- but probably not for longer than 12 months -- testing for anti-HCV should not be done until the infant is at least 12 months of age. There is no practical reason for earlier testing or for the use of RT-PCR for routine diagnosis. Cord blood never should be used for the diagnosis of perinatal HCV infection as cord blood can be contaminated by maternal blood.