Hepatitis C Testing and Treatment Protocol
HCV-antibody testing with reflex HCV RNA polymerase chain reaction testing is the recommended initial screening approach for hepatitis C infection, followed by appropriate treatment based on viral confirmation and disease staging. 1
Recommended Testing Algorithm
Initial Screening
- First-line test: Anti-HCV antibody testing using FDA-approved assays (laboratory-based or point-of-care) 1
- Reflex testing: Positive antibody tests should automatically reflex to HCV RNA testing to confirm active infection 1
- Testing approach: Ideally, use a single blood collection with automatic reflex testing to avoid the need for return visits 1
Special Testing Considerations
- For recent exposure (within 6 months): HCV RNA testing or follow-up antibody testing ≥6 months after exposure 1
- For immunocompromised patients: Consider direct HCV RNA testing as part of initial evaluation 1
- For persons at risk of reinfection after previous clearance: HCV RNA testing is recommended (antibody test will remain positive) 1
- For patients on hemodialysis or immunocompromised: HCV antigen testing can be used as an alternative when RNA testing is unavailable 1, 2
Who Should Be Tested
Universal Screening
- One-time screening for all adults ≥18 years (no upper age limit) 1
Risk-Based Screening
- One-time testing for persons <18 years with risk factors 1
- Annual testing for:
- Periodic testing for anyone with ongoing risk behaviors 1
Pre-Treatment Assessment
- Quantitative HCV RNA testing: Required prior to treatment initiation to document baseline viral load 1
- HCV genotype testing: May be considered when it could alter treatment recommendations 1
- Liver disease assessment: Evaluate for cirrhosis and liver disease severity 1
- HBV co-infection screening: Test all patients for HBsAg and anti-HBc before starting HCV treatment 3, 4
Treatment Protocol
Treatment Regimens
Based on patient characteristics:
Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis (Child-Pugh A):
Patients with decompensated cirrhosis (Child-Pugh B or C):
Liver transplant recipients:
Important Clinical Considerations
Interpretation of results: Patients with positive antibody but negative RNA should be informed they do not have current infection but are not protected from reinfection 1
Monitoring during acute infection: Regular laboratory monitoring (every 4-8 weeks for 6-12 months) until ALT normalizes and HCV RNA becomes undetectable 1
Counseling: Advise patients to avoid hepatotoxic substances (alcohol, certain medications) and prevent transmission 1
Treatment goal: The endpoint of therapy is sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion 1
Common Pitfalls to Avoid
Failing to reflex test: Not automatically ordering HCV RNA testing after a positive antibody test is a major barrier to care 1
Missing acute infections: In early infection, antibody tests may be negative; consider RNA testing for suspected recent exposures 1
Inadequate follow-up: Ensure proper linkage to care for positive cases to prevent loss to follow-up 1
Overlooking HBV co-infection: Failure to screen for HBV before HCV treatment can lead to HBV reactivation 3, 4
Ignoring high-risk populations: Integrate testing services into substance use treatment programs and other settings to reach people who inject drugs 1
The early identification and treatment of HCV infection significantly reduces the risk of liver-related morbidity and mortality by facilitating earlier access to highly effective direct-acting antiviral therapy 5, 6.