What tests should be ordered and when to confirm cure of Hepatitis C (HCV) after treatment with Mavyret (glecaprevir/pibrentasvir)?

Testing for Cure After Mavyret Treatment

You should confirm sustained virologic response (SVR) by measuring HCV RNA at 12 weeks after completing Mavyret treatment, and this single test is sufficient to declare cure in most patients. 1

Primary Testing Timeline

• Measure HCV RNA at 12 weeks post-treatment (SVR12) using a sensitive assay with detection limit ≤25 IU/mL to confirm virologic cure 1, 2
• SVR12 is the definitive endpoint - less than 1% of patients relapse after achieving undetectable HCV RNA at this timepoint with modern direct-acting antivirals like Mavyret 1, 2, 3
• No routine testing beyond 12 weeks post-treatment is necessary unless the patient has ongoing risk factors for reinfection 1, 2

Optional Additional Testing

• Consider testing at 24 weeks post-treatment (SVR24) on an individual basis, though this is no longer routinely recommended since SVR12 has >97% positive predictive value for sustained cure 1, 3
• Testing at 48 weeks post-treatment may be considered but is not supported by strong evidence for routine use 1

Test Selection

• Use quantitative or qualitative HCV RNA PCR testing with FDA-approved assays having detection limits ≤25-50 IU/mL 1, 2
• Do NOT use anti-HCV antibody testing to assess cure, as antibodies persist indefinitely regardless of cure status and cannot distinguish active from resolved infection 2

Long-Term Surveillance Strategy

For Patients WITHOUT Cirrhosis (Stages 0-2 Fibrosis)

• No further HCV RNA testing is needed after confirming SVR12 if HCV RNA remains undetectable and liver enzymes normalize 1, 2
• No hepatocellular carcinoma (HCC) surveillance is recommended for non-cirrhotic patients post-SVR 1
• Patients can be discharged as cured once SVR is confirmed 2

For Patients WITH Cirrhosis (Stage 3-4 Fibrosis)

• Lifelong HCC surveillance every 6 months with abdominal ultrasound ± alpha-fetoprotein is mandatory, regardless of achieving SVR 1, 4, 2, 5
• Endoscopic screening for esophageal varices should be performed initially in all cirrhotic patients, then repeated at 2-3 year intervals post-SVR 1, 4, 2
• Consider cessation of endoscopic screening only if no varices are found 2-3 years post-SVR and there are no other risk factors for progressive cirrhosis 1

For Patients With Ongoing Reinfection Risk

• Annual HCV RNA testing is recommended for patients with persistent risk behaviors including people who inject drugs, men who have sex with men with ongoing high-risk behavior, or any patient with continued exposure risk 2
• Reinfection risk is 1-5% per year in high-risk populations 2

Critical Pitfalls to Avoid

• Do not rely on anti-HCV antibody testing alone - it remains positive after cure and cannot confirm viral eradication 2
• Do not stop HCC surveillance in cirrhotic patients even after achieving SVR, as HCC risk persists indefinitely 1, 4, 2
• Do not use insensitive assays - ensure the HCV RNA test has a lower limit of detection ≤25-50 IU/mL 1, 2
• Do not assume cure if testing earlier than 12 weeks post-treatment - the majority of relapses occur between weeks 4-12 after treatment completion 2, 3

If HCV RNA Remains Detectable

• If HCV RNA is positive at SVR12, this represents virologic relapse and requires retreatment with a different regimen 4
• Perform HCV genotype confirmation and resistance testing before selecting salvage therapy 4
• Do not retreat with the same regimen that failed, as it will almost certainly fail again due to established resistance 4