Hepatitis C is a significant global health concern, often progressing silently without noticeable symptoms for years. A concerning statistic reveals that nearly one in three individuals with hepatitis C are unaware they are infected. Furthermore, a large majority, approximately 75% to 85%, of those with hepatitis C experience no symptoms. This lack of awareness is a critical issue because without proper diagnosis through testing, individuals can unknowingly transmit the virus to others.
Currently, there is no vaccine available to prevent hepatitis C infection. Therefore, the most effective preventive measure is to avoid behaviors that are known to transmit the virus. Early and accurate diagnosis is paramount for managing hepatitis C, preventing further transmission, and initiating timely treatment.
Who Should Be Tested for Hepatitis C? Updated Guidelines for Diagnosis
For healthcare providers seeking guidance on hepatitis C testing for their patients, comprehensive resources are available, such as the Hepatitis C Testing guidelines.
Universal screening recommendations are crucial for broad detection and management of hepatitis C. Clinicians are advised to screen:
- All adults aged 18 years and older should undergo hepatitis C virus (HCV) testing at least once in their lifetime. An exception is made for settings with extremely low HCV prevalence (below 0.1% HCV RNA-positivity).
- All pregnant women should be screened for HCV during each pregnancy, again with the exception of settings where HCV prevalence is under 0.1%.
In addition to universal screening, the CDC recommends one-time hepatitis C testing for individuals with recognized risk factors or past exposures. These risk factors include:
- Individuals who currently inject drugs or have a history of injection drug use, especially those who shared needles, syringes, or drug preparation equipment.
- People living with human immunodeficiency virus (HIV).
- Individuals with specific medical conditions, such as those who have received long-term hemodialysis and individuals with persistently elevated alanine aminotransferase (ALT) levels.
- Recipients of blood transfusions or organ transplants prior to enhanced screening measures:
- People who received clotting factor concentrates produced before 1987.
- Individuals who received a blood transfusion or blood components before July 1992.
- People who underwent organ transplantation before July 1992.
- People who were informed that they received blood from a donor who later tested positive for HCV.
- Healthcare workers, emergency medical personnel, and public safety staff who have experienced needle stick injuries, sharps exposures, or mucosal contact with HCV-positive blood.
- Infants born to mothers known to have hepatitis C.
Regular, periodic hepatitis C testing is also recommended by the CDC for patients with ongoing risk factors, irrespective of the general prevalence in their setting. This includes:
- People who continue to inject drugs and share needles, syringes, or drug preparation equipment.
- Individuals with certain medical conditions, including those receiving maintenance hemodialysis.
It is also important for clinicians to offer hepatitis C testing to anyone who requests it, regardless of whether they report traditional risk factors. Patients may be reluctant to disclose stigmatized behaviors, making open access to testing essential.
Hepatitis C Screening and Diagnostic Testing Procedures
The recommended initial step in hepatitis C diagnosis is an HCV antibody test. If this antibody test is positive or reactive, it should be followed by a Nucleic Acid Test (NAT) for HCV RNA. For a detailed visual representation of this process, refer to the complete testing sequence flowchart.
If a patient’s antibody test is reactive, and HCV RNA is detected, it indicates a current HCV infection. In such cases, patient counseling is crucial, and evaluation for treatment with an appropriate direct-acting antiviral (DAA) regimen should be initiated.
Recommended Testing Sequence for Identifying Current HCV Infection
Streamlining Hepatitis C Diagnosis: Operational Guidance
To expedite diagnosis, evaluation, and the start of treatment, the CDC advocates for collecting all necessary samples for hepatitis C diagnosis during a single patient visit. Furthermore, automatic ordering of HCV RNA testing when the HCV antibody test is reactive is highly recommended. This reflex testing protocol, where laboratories automatically perform NAT testing for HCV RNA upon a reactive antibody result, significantly streamlines the diagnostic pathway, requiring no additional action from either the patient or the clinician. For comprehensive recommendations, consult the CDC guidelines on updated operational guidance for hepatitis C testing.
Understanding False Negative Possibilities in Hepatitis C Antibody Testing
It’s important to be aware that false negative results can occur with HCV antibody tests, particularly during acute HCV infection. Antibodies may not become detectable until 8 to 11 weeks post-infection. Therefore, in cases of suspected recent exposure, a negative antibody test may not definitively rule out infection. Additionally, some individuals may not mount a sufficient immune response to produce detectable antibodies within this timeframe. In these scenarios, virologic testing, specifically HCV RNA testing, should be considered.
Utilizing HCV RNA Testing for Recent Hepatitis C Infection
HCV RNA testing is particularly valuable in diagnosing current HCV infection in individuals who may have been exposed to HCV within the previous 6 months, regardless of the HCV antibody test result. HCV RNA can be detected as early as 1 to 2 weeks after HCV infection. Suspicion of recent exposure may arise from a patient’s medical history or the context of the patient encounter, such as individuals who inject drugs presenting at a syringe service program.
Point-of-Care Testing for Hepatitis C: Implementation Considerations
The implementation of point-of-care (POC) HCV testing can vary significantly depending on the setting. There is no universal approach, and each site needs to consider its unique characteristics when deciding whether and how to implement POC HCV testing.
Both laboratory-based and POC tests are available for HCV antibody and HCV RNA detection. Choosing the optimal testing strategy requires careful consideration of various factors. The CDC document, “Considerations for the Implementation of Point-of-Care Testing for the Diagnosis of Hepatitis C Virus Infection,” provides detailed guidance on selecting the most appropriate testing approach, determining suitable locations for different testing modalities, and developing strategies to link HCV screening and testing with readily accessible treatment options.
Recommended Hepatitis C Diagnostic Tests
Clinicians are advised to use an FDA-approved HCV antibody test as the initial screening test, followed by a NAT for HCV RNA if the antibody test is positive or reactive. Recommended tests include:
- HCV antibody test (anti-HCV), such as an enzyme immunoassay (EIA). This test detects the presence of antibodies to the hepatitis C virus, indicating past or current exposure.
- Nucleic acid test (NAT) for HCV RNA (qualitative RNA test). This test detects the presence of the virus’s genetic material and confirms current infection.
- NAT to quantify HCV RNA levels (quantitative RNA test). This test measures the amount of virus in the blood and is used for monitoring treatment response.
A reactive HCV antibody test indicates a history of HCV exposure, which could be due to a current or past infection (including resolved infection). A detectable HCV RNA test result definitively indicates a current, active HCV infection.
For individuals with suspected HCV exposure within the last 6 months, NAT for HCV RNA detection should be used, even if the antibody test is negative.
For infants born to mothers with hepatitis C, HCV RNA testing using NAT should be performed at 2–6 months of age. Infants with detectable HCV RNA require coordinated care with a pediatric hepatitis C specialist. Infants with undetectable HCV RNA generally do not need further follow-up unless clinically indicated.
Interpreting Hepatitis C Test Results: A Guide for Clinicians
Accurate interpretation of hepatitis C test results is essential for appropriate patient management. The following table summarizes the interpretation of different test outcomes and recommended further actions:
Interpretation of Hepatitis C Test Results and Further Actions
| Test Outcome | Interpretation | Further Actions
