How to monitor viral response in an adult patient with confirmed Hepatitis C Virus (HCV) infection treated with Direct-Acting Antivirals (DAAs)?

Monitoring Viral Response in HCV Patients Treated with DAAs

Confirm sustained virologic response (SVR) by testing HCV RNA at 12 weeks after completing DAA treatment—this single post-treatment timepoint is the standard endpoint that defines virologic cure. 1

During Treatment Monitoring

On-Treatment HCV RNA Testing

• On-treatment laboratory monitoring is NOT required for most patients receiving DAAs unless treatment-related side effects occur or adherence concerns arise 1
• For patients receiving DAA regimens, viral kinetics during treatment do not predict SVR and routine monitoring adds limited clinical value 1, 2, 3
• If monitoring is performed during treatment, HCV RNA can be measured at weeks 4,8, and 12-24 of treatment or at end of treatment, though this is not mandatory 1

Stopping Rules (When Applicable)

• For older combination regimens with simeprevir + peginterferon + ribavirin: stop if HCV RNA >25 IU/mL at week 4 with good compliance 1
• For sofosbuvir + peginterferon + ribavirin: consider stopping if HCV RNA is detected at week 4 with good compliance 1
• For interferon-free DAA regimens, there are no clear stopping criteria, but if HCV RNA exceeds 25 IU/mL at week 4, retest at week 6 and consider stopping if levels remain ≥1 log or are elevated 1

Post-Treatment Monitoring

Primary Assessment of Treatment Success

• Test HCV RNA at 12 weeks post-treatment (SVR12) to confirm virologic cure—undetectable HCV RNA at this timepoint represents sustained virologic response and virologic cure 1
• SVR12 has replaced SVR24 as the primary endpoint with DAA regimens, with fewer than 1% of patients relapsing after achieving SVR12 1

Extended Post-Treatment Monitoring

• Routine confirmation of SVR at 48 weeks post-treatment is recommended 1
• Testing at 24 weeks post-treatment should be considered on an individual patient basis 1
• Routine testing for HCV RNA beyond 48 weeks to evaluate for late virologic relapse is NOT supported by evidence 1

Monitoring for Reinfection

• Periodic HCV RNA testing is recommended only for patients with ongoing risk factors for reinfection (e.g., people who inject drugs, men who have sex with men with high-risk practices) 1, 4
• For patients with ongoing risk factors, perform HCV RNA testing annually or anytime hepatic aminotransferase levels increase 1, 4
• Recurrent viremia after SVR represents either reinfection or relapse; with reinfection, treatment approaches are identical to initial treatment 1

Alternative Monitoring: HCV Core Antigen Testing

When HCV Core Antigen May Be Used

• HCV core antigen (HCVAg) testing can monitor DAA efficacy as well as HCV RNA assays and may be preferred from an economical and organizational perspective 2, 3, 5
• HCVAg shows good concordance (kappa = 0.62) and correlation with HCV RNA testing 3
• At end of treatment, undetectable HCVAg showed sensitivity 74%, specificity 100%, NPV 97%, and PPV 100% for predicting SVR 5

Limitations of HCV Core Antigen

• HCVAg becomes undetectable more slowly than HCV RNA during treatment (71% vs 10% at week 2,84% vs 43% at week 4) 2
• Measurement of HCV RNA after treatment is needed to rule out relapse in HCVAg-positive patients 2
• Both HCVAg and HCV RNA have limited predictive value for SVR when measured during DAA treatment 3

Long-Term Post-SVR Management

Patients With Cirrhosis or Advanced Fibrosis

• Surveillance for hepatocellular carcinoma (HCC) with liver imaging ± serum AFP should be pursued twice annually indefinitely for all patients with stage 3 fibrosis or cirrhosis post-SVR 1
• Initial endoscopic screening for esophagogastric varices is recommended for all cirrhotic patients, independent of SVR 1
• Repeat endoscopic screening at 2-3 years post-SVR if no varices or small varices were identified initially 1
• Assessment for liver disease progression every 6-12 months is recommended if retreatment is delayed or not feasible 1

Patients Without Advanced Fibrosis

• HCC surveillance is NOT recommended for patients with stages 0-2 fibrosis post-SVR 1
• In the absence of cirrhosis, persons who attain SVR require no liver-specific follow-up 1

Monitoring for Other Liver Disease

• Patients who achieve SVR but have persistently elevated hepatic aminotransferase levels require evaluation for other causes of liver disease (alcohol, fatty liver, other hepatotoxins) 1
• Counsel all patients regarding sources of liver injury that can independently contribute to fibrosis progression 1
• Regular liver enzyme monitoring is recommended, with any elevation prompting immediate HCV RNA testing in those with ongoing risk factors 4

Special Monitoring Considerations

HBV Coinfection

• Test all patients for current or prior HBV infection (HBsAg and anti-HBc) before initiating DAA treatment 6, 7, 8
• Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up 6, 7, 8

Concomitant Medications

• Patients taking diabetes medications should have glucose monitoring during and after DAA treatment due to potential for symptomatic hypoglycemia; dosage adjustments may be needed 1
• Patients taking warfarin require INR monitoring for subtherapeutic anticoagulation during and after DAA treatment; warfarin dosage adjustments may be needed 1