After a needlestick or mucosal exposure to blood from a known or suspected hepatitis C virus–positive source, what post‑exposure prophylaxis is recommended?

Hepatitis C Post-Exposure Prophylaxis

No immunoglobulin or antiviral agents are recommended for post-exposure prophylaxis after needlestick or mucosal exposure to hepatitis C virus—the standard of care is baseline and serial testing with early referral to a specialist if infection is detected. 1

Why No Prophylaxis Exists

The CDC explicitly states that neither immune globulin (IG) nor antiviral agents should be administered as post-exposure prophylaxis for hepatitis C. 1 This recommendation has remained consistent across multiple guideline iterations and reflects several key factors:

• Low transmission risk: The average risk of HCV transmission after percutaneous exposure to infected blood is approximately 1.8% (range 0-7%), which is substantially lower than hepatitis B. 2
• Lack of efficacy data: No adequately powered clinical trials have demonstrated that antiviral prophylaxis prevents HCV infection after exposure. 3, 4
• Cost-effectiveness concerns: Even with modern direct-acting antivirals (DAAs), the low transmission rate makes prophylaxis economically unjustifiable. 4, 5
• Natural history considerations: A significant proportion of acute HCV infections resolve spontaneously, and early treatment of confirmed acute infection achieves excellent cure rates. 6, 4

Recommended Post-Exposure Management Protocol

Immediate Actions (Within 48 Hours)

Test the source patient immediately using one of two CDC-recommended approaches: 7

1. Preferred option: Test directly for HCV RNA using nucleic acid testing (NAT), particularly if the source has recent high-risk behaviors (e.g., injection drug use within 4 months) or if risk cannot be reliably assessed. 7
2. Alternative option: Test for anti-HCV antibody first, then reflex to HCV RNA if positive. 7

Test the exposed healthcare worker at baseline for anti-HCV with reflex to HCV RNA if positive, ideally within 48 hours of exposure. 7

Follow-Up Testing Schedule

If the source is HCV RNA-positive or anti-HCV-positive with unavailable RNA results: 7

• At 3-6 weeks post-exposure: Test the exposed person for HCV RNA using NAT for early diagnosis. 1, 7
• At 4-6 months post-exposure: Test for anti-HCV and ALT activity to assess seroconversion. 1, 7
• Confirm all positive anti-HCV results with supplemental testing (not just enzyme immunoassay alone). 1, 2

If the source is HCV-negative or the exposure involves mucous membranes with unknown source status: Generally no follow-up testing is required, though testing may be considered if exposure to an HCV-infected source is highly likely based on epidemiologic assessment. 1

Critical Management Points

When HCV Infection Is Detected Early

Immediate specialist referral is mandatory. 1 The CDC notes that while limited data suggest antiviral therapy may be beneficial when started early in acute HCV infection, no formal guidelines exist for treatment timing during the acute phase—this decision must be made by a specialist experienced in hepatitis C management. 1

Modern evidence suggests that interferon monotherapy (in older literature) or DAAs (current era) can achieve high cure rates when initiated during acute infection, with earlier treatment associated with better outcomes. 6 However, the 2020 AASLD/IDSA guidelines recommend treatment for all chronic HCV infections, and specialists may elect to treat acute infection based on individual circumstances. 1

Baseline Testing Components

For the exposed healthcare worker, obtain: 2

• Anti-HCV antibody (with reflex to HCV RNA if positive)
• Alanine aminotransferase (ALT) level
• Document hepatitis B vaccination status and immunity (anti-HBs)
• HIV testing if not recently documented

Counseling During Follow-Up Period

Advise exposed persons to: 1, 2

• Seek immediate medical evaluation for any acute illness during the follow-up period (fever, fatigue, jaundice, abdominal pain)
• Avoid donating blood, organs, tissue, or semen until cleared
• Use barrier precautions during sexual activity if multiple partners or sexually transmitted infections are present (though sexual transmission risk is low in monogamous relationships)
• Avoid sharing toothbrushes, razors, or other items that might contact blood

Common Pitfalls to Avoid

Do not administer antiviral prophylaxis "just in case"—this is explicitly not recommended and wastes resources while exposing the worker to unnecessary drug toxicity. 1, 4

Do not skip the 3-6 week HCV RNA test if early diagnosis is desired—waiting only for the 4-6 month antibody test delays identification of acute infection by months. 7

Do not test discarded needles or syringes for virus contamination—results are unreliable and should not guide management. 2

Do not assume immunity exists—unlike hepatitis B, there is no vaccine and no post-exposure immunoglobulin that provides protection. 1

Do not fail to complete the full 6-month follow-up testing—seroconversion can be delayed, and early negative tests do not rule out infection. 2

Special Populations

For infants born to HCV-positive mothers: IG and antiviral agents are also not recommended for prophylaxis. Test for anti-HCV at ≥12 months of age (when maternal antibodies have waned), or use HCV RNA testing at 1-2 months if earlier diagnosis is needed. 1

For correctional facility exposures: The same testing and management algorithm applies, with emphasis on discharge planning that includes referral to medical care and risk-reduction programs. 1