Hepatitis C Screening and Treatment for High-Risk Individuals
All adults aged 18 years and older should receive universal, one-time, opt-out HCV screening using HCV-antibody testing with reflex HCV RNA PCR testing, regardless of perceived risk factors. 1, 2
Universal Screening Approach
The American Association for the Study of Liver Diseases (AASLD-IDSA) recommends universal screening for all adults ≥18 years without an upper age limit, moving beyond the previous birth cohort approach (1945-1965) to capture younger populations affected by the opioid epidemic and injection drug use. 1
This universal screening strategy is cost-effective, aligns with WHO goals to eliminate HCV as a public health threat by 2030, and bypasses the inherent barriers in obtaining accurate risk factor assessments. 1
The reflex testing approach (antibody with automatic RNA confirmation if positive) requires only a single blood collection, eliminating the need for return visits and addressing a major barrier in the HCV care continuum. 2
High-Risk Populations Requiring Periodic Screening
Beyond universal one-time screening, certain high-risk groups require periodic repeat testing based on ongoing exposure risk:
Annual Testing Required:
- People who inject drugs (PWID) - due to high incidence and prevalence of HCV in this population 1
- HIV-positive men who have sex with men (MSM) with unprotected sex - this group has 4.1 times higher risk of acquiring HCV compared to HIV-negative MSM, with incidence of 6.08/1000 person-years 1, 3
Risk-Based Periodic Testing (frequency at clinician discretion):
- Persons with ongoing injection drug use or intranasal drug use 1
- Persons on long-term hemodialysis 1
- Healthcare workers after needlestick or mucosal exposure to HCV-positive blood 1
- Persons with HIV infection (if not already on annual testing schedule) 1
- Children born to HCV-infected mothers 1
- Persons with current sexual contact with HCV-infected individuals 1
One-Time Risk-Based Testing:
- Persons who received blood transfusions or organ transplants prior to 1992 1
- Persons younger than 18 years with any of the above risk factors 1
Initial Testing Strategy
Step 1: HCV Antibody Testing
- Use FDA-approved enzyme immunoassay (EIA) as the initial screening test 2
- A negative antibody test indicates no evidence of current or past infection (unless recent exposure within 6 months or immunocompromised) 2
Step 2: Reflex HCV RNA PCR Testing
- Automatically performed if antibody is positive, without requiring a second visit 2
- Confirms active infection and distinguishes current from resolved infection 2
Interpretation of Results
- Positive antibody + Positive RNA = Active HCV infection requiring treatment evaluation 2
- Positive antibody + Negative RNA = Past resolved infection or false positive; patient does not have current infection but is not protected from reinfection 2
- Negative antibody = No evidence of infection (with caveats below) 2
Special Testing Considerations
Recent Exposure (Within 6 Months):
- For individuals with negative antibody tests who had recent exposure, perform HCV RNA testing or follow-up HCV-antibody testing ≥6 months after exposure, as antibodies may not yet be detectable 1, 2
Immunocompromised Patients:
- Consider direct HCV RNA testing rather than antibody testing, as antibody production may be delayed or inadequate 2
Previously Infected Patients:
- Use HCV RNA testing only for reinfection monitoring, as antibody tests will remain positive after prior clearance 2
Resource-Limited Settings:
- Dried blood spot collection can be used for sequential antibody and reflex RNA testing in rural or difficult-to-access populations, requiring only a fingerstick rather than venipuncture 2
Pre-Treatment Evaluation
Once active HCV infection is confirmed:
- Quantitative HCV RNA testing to establish baseline viral load prior to antiviral therapy 2
- HCV genotype testing may be considered, though becoming less necessary with pangenotypic direct-acting antiviral (DAA) regimens that cure >90% of patients 2, 4
- Assessment for liver fibrosis stage and cirrhosis 1
- Screening for hepatocellular carcinoma in appropriate patients 1
Treatment Recommendations
- All patients with confirmed HCV infection should be evaluated for treatment with direct-acting antivirals (DAAs), which achieve sustained virological response (cure) in >90% of patients 4
- Treatment regimens typically involve combination of 2-3 DAAs targeting NS3/4A protease, NS5A protein, and NS5B polymerase 4
- Treatment duration ranges from 8-24 weeks depending on genotype, treatment history, and presence of cirrhosis 5
Common Pitfalls to Avoid
Relying solely on antibody testing will miss active infections and incorrectly classify resolved infections as current - always use reflex RNA testing 2, 6
Missing the window period - both antibody and RNA may be negative in the first 6 weeks after acute exposure; repeat testing is essential for recent exposures 7
Overlooking reinfection in previously treated patients - antibody tests remain positive after clearance, so only RNA testing can detect reinfection 2
Failing to implement reflex testing protocols leads to patients being lost to follow-up between antibody and confirmatory testing 2
Underestimating risk in HIV-negative MSM - recent data shows similar high-risk behaviors between HIV-positive and HIV-negative MSM, with new HCV diagnoses occurring in both groups 8
Missing immunocompromised patients who may have false-negative antibody tests despite active infection 2