Hepatitis C virus (HCV) infection is a significant global health concern, and alarmingly, nearly one in three individuals infected with hepatitis C are unaware of their status. Furthermore, a large majority, approximately 75%–85%, of those with hepatitis C may not experience noticeable symptoms. This silent nature of the infection is a critical issue because without proper Hepatitis C Virus Diagnosis and testing, individuals can unknowingly transmit the virus to others.
Currently, there is no vaccine available to prevent hepatitis C. Therefore, the most effective strategy for prevention is to avoid behaviors that can lead to virus transmission.
Who Should Be Tested for Hepatitis C? Guidelines for Clinicians
To facilitate timely hepatitis C virus diagnosis and care, clinicians should implement universal screening protocols. The guidelines recommend:
- Universal One-Time Screening: All adults aged 18 years and older should be screened at least once in their lifetime. This is a broad recommendation, except for settings where the prevalence of chronic HCV infection (HCV RNA-positivity) is exceptionally low, specifically below 0.1%.
- Screening During Pregnancy: All pregnant women should be screened for HCV during each pregnancy. Similar to adult screening, an exception is made for settings with very low HCV prevalence (under 0.1%).
In addition to universal screening, targeted hepatitis C virus diagnosis is crucial for individuals with recognized risk factors or exposures. The Centers for Disease Control and Prevention (CDC) recommends one-time hepatitis C testing for the following groups:
- People Who Inject Drugs (PWID): Individuals who currently or have a history of injecting drugs, especially those who shared needles, syringes, or drug preparation equipment. This is a major risk factor for HCV transmission.
- Individuals with HIV: People with human immunodeficiency virus (HIV) infection are at higher risk for HCV co-infection.
- Selected Medical Conditions:
- Hemodialysis Patients: People who have ever received maintenance hemodialysis are at increased risk due to potential exposure in healthcare settings.
- Elevated ALT Levels: Individuals with persistently abnormal alanine aminotransferase (ALT) levels, which can indicate liver damage, should be tested for HCV.
- Prior Transfusion or Transplant Recipients:
- Clotting Factor Concentrates Before 1987: Recipients of clotting factor concentrates produced before 1987 are at risk due to less stringent screening of blood products at that time.
- Blood Transfusion Before July 1992: People who received a transfusion of blood or blood components before July 1992, when more sensitive HCV screening of blood donations became standard.
- Organ Transplant Before July 1992: Individuals who received an organ transplant before July 1992, due to similar reasons as blood transfusions.
- Notification of HCV-Positive Donor: People notified that they received blood from a donor who later tested positive for HCV infection.
- Healthcare and Public Safety Personnel: Health care, emergency medical, and public safety personnel after needle sticks, sharps injuries, or mucosal exposures to HCV-positive blood.
- Infants Born to HCV-Positive Mothers: Infants born to individuals with known hepatitis C, as perinatal transmission is possible.
Furthermore, routine periodic hepatitis C virus diagnosis is recommended for patients with ongoing risk factors, regardless of the setting’s HCV prevalence. These include:
- Current PWID: People who continue to inject drugs and share equipment.
- Maintenance Hemodialysis Patients: Individuals receiving ongoing maintenance hemodialysis.
It is also important to note that clinicians should offer hepatitis C testing to anyone who requests it, irrespective of self-reported risk factors. Patients may be hesitant to disclose stigmatizing behaviors, making open access to testing essential for comprehensive hepatitis C virus diagnosis efforts.
Hepatitis C Screening and Diagnostic Testing Procedures
The recommended initial test for hepatitis C virus diagnosis is an HCV antibody test. This blood test detects antibodies to the hepatitis C virus, indicating past or present exposure to HCV.
Reflex to HCV RNA Testing: If the HCV antibody test is positive or reactive, it should be followed by a nucleic acid test (NAT) for HCV RNA. This is known as “reflex testing”. The HCV RNA test detects the genetic material of the virus and is crucial for confirming current HCV infection. A positive HCV RNA test indicates active infection, while a negative result in someone antibody-positive usually indicates resolved past infection.
Streamlining Hepatitis C Virus Diagnosis: Operational Guidance
To improve the efficiency of hepatitis C virus diagnosis and accelerate the pathway to treatment, the CDC recommends a streamlined approach. This involves collecting all necessary samples for diagnosis during a single patient visit and automatically ordering HCV RNA testing when the HCV antibody test is reactive. This automatic reflex testing eliminates delays and the need for additional patient visits, significantly improving the speed of diagnosis and linkage to care.
Understanding False Negative Results in Early Infection
It’s important to be aware of the possibility of false negative HCV antibody results, especially in cases of recent HCV infection. Antibodies may not become detectable until 8–11 weeks after infection. Therefore, individuals who suspect recent exposure and test negative for HCV antibodies should be considered for virologic testing, specifically HCV RNA testing. Similarly, some individuals may have weakened immune responses and not develop detectable antibodies within this timeframe, also necessitating HCV RNA testing if infection is suspected.
HCV RNA Testing for Recent Hepatitis C Infection
For individuals who may have been exposed to HCV within the past 6 months, HCV RNA testing is recommended regardless of the HCV antibody test result. HCV RNA becomes detectable much earlier than antibodies, typically within 1-2 weeks after infection. This is particularly relevant for individuals with known recent risk factors, such as PWID presenting to syringe service programs, where recent exposure may be inferred.
Point-of-Care Testing for Hepatitis C Virus Diagnosis
Point-of-care (POC) HCV testing offers opportunities to expand access to hepatitis C virus diagnosis, particularly in settings where rapid results are beneficial, such as outreach programs, emergency departments, and primary care clinics. Both POC antibody and RNA tests are available. The selection of a testing strategy should consider various factors, including testing volume, resources, patient population, and linkage to care pathways. Implementing POC testing requires careful planning to ensure efficient workflow, quality control, and seamless connection to treatment services.
Recommended Tests for Hepatitis C Virus Diagnosis
For accurate hepatitis C virus diagnosis, clinicians should utilize FDA-approved tests. The recommended testing algorithm includes:
- HCV Antibody Test (Anti-HCV): This is typically an enzyme immunoassay (EIA). A reactive result indicates HCV exposure.
- Qualitative HCV RNA Test: A nucleic acid test (NAT) to detect the presence of HCV RNA. This confirms current infection in antibody-positive individuals.
- Quantitative HCV RNA Test: A NAT to measure the level of HCV RNA (viral load). This is primarily used for monitoring treatment response and is not essential for initial hepatitis C virus diagnosis.
For suspected recent HCV exposure (within 6 months), NAT for HCV RNA is the recommended diagnostic test, even if the antibody test is negative.
In infants born to mothers with hepatitis C, HCV RNA testing using NAT should be performed at 2–6 months of age for hepatitis C virus diagnosis. Infants with detectable HCV RNA require specialist care, while those with undetectable RNA generally do not need further HCV-related follow-up unless clinically indicated.
Interpreting Hepatitis C Screening Results
Accurate interpretation of hepatitis C test results is crucial for appropriate clinical management. The following table summarizes test outcomes, interpretations, and recommended actions:
Hepatitis C Test Result Interpretation and Actions
| Test Outcome | Interpretation | Further Actions |
|---|---|---|
| HCV antibody nonreactive | No HCV antibody detected | Report as negative for HCV antibody. No further action needed unless recent exposure is suspected, in which case, test for HCV RNA.* |
| HCV antibody reactive | Presumptive HCV infection | A reactive result may indicate current infection, resolved past infection, or a false positive. Perform HCV RNA test to determine current infection status. |
| HCV antibody reactive, HCV RNA detected | Current HCV infection | Provide counseling and link to care and treatment.† |
| HCV antibody reactive, HCV RNA not detected | No current HCV infection | In most cases, no further action is needed. To differentiate between true positive and false positive antibody results, and if the initial test is repeatedly reactive, consider repeat antibody testing with a different assay. In specific cases, follow up with HCV RNA testing and appropriate counseling.§ |
* If HCV RNA testing is not feasible and the person is not immunocompromised, follow-up antibody testing to demonstrate seroconversion may be considered. In immunocompromised individuals, HCV RNA testing is preferred if recent exposure is suspected.
† It is recommended to retest for HCV RNA in a subsequent sample to confirm positivity before initiating antiviral therapy.
§ Follow up with HCV RNA testing and counseling if recent HCV exposure (within 6 months) is suspected, clinical evidence of HCV disease exists, or there are concerns about specimen handling or storage.
Diagnosing Hepatitis C: A Step-by-Step Approach
In summary, hepatitis C virus diagnosis involves a clear sequence of steps:
- Initial Screening with HCV Antibody Test: If the antibody test is nonreactive (negative), HCV infection is unlikely, unless recent exposure is a concern.
- Confirmation with HCV RNA Test: If the antibody test is reactive (positive), an HCV RNA test is necessary to confirm current infection.
- Early RNA Detection: HCV RNA becomes detectable earlier than antibodies, typically 1-2 weeks post-exposure, making it valuable for diagnosing acute infection.
- Streamlined Testing: Current guidelines recommend automatic HCV RNA reflex testing for all antibody-reactive samples to expedite diagnosis and treatment initiation.
What Happens After a Hepatitis C Virus Diagnosis?
Following a hepatitis C virus diagnosis, the CDC recommends offering the following services:
- Medical Evaluation: Comprehensive medical evaluation by a primary care clinician or specialist in liver disease for treatment and ongoing monitoring of chronic hepatitis C.
- Hepatitis A and B Vaccination: Vaccination against hepatitis A and B to prevent additional liver damage from other hepatitis viruses.
- Alcohol Consumption Screening and Intervention: Screening and brief intervention for alcohol use, as alcohol can exacerbate liver disease.
- HIV Risk Assessment and Testing: HIV risk assessment and testing, as HIV and HCV co-infection is common and impacts management.
For detailed recommendations on testing, management, and treatment, refer to resources from the CDC and the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA).
Reporting Hepatitis C Cases
Hepatitis C, including acute, chronic, and perinatal cases, is a nationally notifiable condition. Healthcare providers are required to report suspected cases of healthcare-associated HCV infection to public health authorities for investigation and response. Specific event codes are used for reporting acute, chronic, and perinatal hepatitis C cases to the National Notifiable Diseases Surveillance System (NNDSS).
Resources for Hepatitis C Virus Diagnosis and Management
Several valuable resources are available to support hepatitis C virus diagnosis and patient care:
Downloadable Resources:
Scientific Guidelines and Recommendations:
- Updated Operational Guidance for Implementing CDC’s Recommendations on Testing for Hepatitis C Virus Infection
- CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children — United States, 2023
- CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020
Other Resources:
- Recommendations for Testing, Managing, and Treating Hepatitis C (AASLD and IDSA)
By understanding the importance of hepatitis C virus diagnosis, adhering to testing guidelines, and utilizing available resources, we can work towards reducing the burden of hepatitis C and improving patient outcomes.
