What are the recommendations for Hepatitis C (HCV) screening and treatment?

Hepatitis C Screening Recommendations

Primary Recommendation

All adults aged 18-79 years should receive universal, one-time screening for hepatitis C virus (HCV) infection, regardless of risk factors. 1, 2

Who Should Be Screened

Universal Screening

• Adults aged 18-79 years require one-time HCV screening regardless of the presence or absence of risk factors, as recommended by the U.S. Preventive Services Task Force in 2020. 1
• The American Association for the Study of Liver Diseases (AASLD) recommends universal screening for all adults aged 18 years and older without an upper age limit, citing excellent quality of life in many octogenarians and more rapid disease progression with advanced age. 1
• All pregnant women should be screened during each pregnancy, as HCV prevalence has doubled in women aged 15-44 years from 2006 to 2014, with a 68% increase in infants born to HCV-infected mothers. 1, 3

Risk-Based Screening for Special Populations

• Persons younger than 18 years with risk factors (particularly injection drug use history) should undergo screening. 1, 2
• Persons older than 79 years with risk factors should be considered for screening. 1

Periodic Screening for Ongoing Risk

• People who inject drugs require annual testing due to continued risk of new infection. 2, 3
• Men with HIV who have unprotected sex with men require annual testing. 2
• Persons with continued risk factors should receive periodic screening, though optimal frequency remains undefined for most risk groups. 1, 2

Screening Test Methodology

Initial Testing Approach

Use HCV antibody testing with reflex HCV RNA PCR testing as the initial screening strategy, requiring only a single blood draw. 2, 4 This two-step reflex approach eliminates the need for return visits for confirmatory testing and addresses a major barrier in the HCV care continuum. 2

Test Interpretation

• Positive antibody + positive RNA = current active infection requiring treatment evaluation. 2, 4
• Positive antibody + negative RNA = past resolved infection or false positive; patient does not have current infection but is not protected from reinfection. 2, 4
• Negative antibody = no evidence of current or past infection, unless recent exposure or immunocompromised status. 2, 4

Special Testing Scenarios

Recent Exposure (Within 6 Months)

If initial antibody test is negative in persons with recent exposure, perform direct HCV RNA testing or repeat antibody testing ≥6 months after exposure, as antibody production may be delayed 8-9 weeks. 2, 4

Immunocompromised Patients

Consider direct HCV RNA testing for immunocompromised patients, as antibody production may be delayed or inadequate. 2, 4

Previously Infected Patients at Risk for Reinfection

Use HCV RNA testing rather than antibody testing to detect reinfection, since antibody tests remain positive after prior clearance. 2, 4

Hard-to-Access Populations

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 Testing

Once active HCV infection is confirmed (positive HCV RNA):

• Obtain quantitative HCV RNA viral load to establish baseline. 2, 4
• HCV genotype testing may be considered when it would alter treatment recommendations, though this is becoming less necessary with pangenotypic direct-acting antiviral regimens. 2, 4
• Perform complete blood count, comprehensive metabolic panel, hepatic function panel, and INR before initiating therapy. 4
• Test for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment, as HBV reactivation has been reported during HCV treatment with direct-acting antivirals. 5, 6, 4
• HIV antibody testing is recommended due to overlapping risk factors. 4

Rationale for Universal Screening

The shift from birth cohort (1945-1965) screening to universal screening is driven by:

• HCV incidence nearly quadrupled from 2010 to 2017, primarily from increased injection drug use related to the opioid epidemic. 1
• Most new HCV infections now occur in persons born after 1965, with those aged 20-39 years accounting for the majority of cases. 1
• Risk-based screening failed to identify the majority of individuals with HCV infection due to both clinician and patient barriers. 1
• Universal screening is cost-effective (<$30,000/quality-adjusted life years) compared with birth-cohort screening. 1

Common Pitfalls to Avoid

• Never rely solely on antibody testing, as this misses the distinction between active and resolved infection. 2, 4
• Do not use antibody testing to detect reinfection in previously infected patients; antibodies remain positive after clearance—use HCV RNA instead. 2, 4
• Ensure reflex RNA testing is implemented to avoid loss to follow-up between antibody and confirmatory testing. 2, 4
• Do not overlook screening in high-risk groups, especially people who inject drugs or immunocompromised patients. 2
• Remember that immunocompromised patients may have false-negative antibody tests; consider direct RNA testing in these populations. 2, 4

Screening Implementation

Screening should be voluntary and undertaken only with the patient's knowledge, using an opt-out approach where patients are informed orally or in writing that HCV testing will be performed unless they decline. 1 Before screening, patients should receive an explanation of HCV infection, how it can and cannot be acquired, the meaning of positive and negative test results, and the benefits and harms of treatment. 1