What is the recommended treatment for a patient with confirmed active Hepatitis C (HCV) infection based on HCV RNA detection?

Treatment of Confirmed Active Hepatitis C Infection

All patients with confirmed active HCV infection (positive HCV RNA) should be treated with pangenotypic direct-acting antiviral (DAA) regimens, specifically sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients without cirrhosis. 1, 2

Confirmation of Active Infection

• Positive HCV RNA confirms current active infection requiring treatment, distinguishing it from past resolved infection where only antibodies would be present 3, 4
• HCV RNA testing should use a sensitive molecular method with a lower limit of detection ≤15 IU/ml 1
• Quantitative HCV RNA (viral load) should be measured at baseline prior to treatment initiation 4

First-Line Treatment Regimens

Treatment-Naïve Patients Without Cirrhosis

• Sofosbuvir/velpatasvir (400mg/90mg) once daily for 12 weeks 1, 2
• Glecaprevir/pibrentasvir (300mg/120mg) once daily for 8 weeks 1, 2, 5
• Both regimens are pangenotypic and effective for HCV genotypes 1-6 1, 2

Treatment-Naïve Patients With Compensated Cirrhosis

• Sofosbuvir/velpatasvir for 12 weeks 1
• Glecaprevir/pibrentasvir for 12 weeks (extended from 8 weeks due to cirrhosis) 1, 5

Treatment-Experienced Patients

• Duration varies by prior treatment history and presence of cirrhosis 1
• Patients previously treated with NS5A inhibitors require 16 weeks of glecaprevir/pibrentasvir 5
• Patients previously treated with NS3/4A protease inhibitors (without NS5A inhibitor) require 12 weeks 5

Treatment Goal and Success Definition

• The goal is to eradicate HCV infection to prevent cirrhosis, hepatocellular carcinoma, and death 1, 4
• Treatment success is defined as sustained virologic response (SVR12): undetectable HCV RNA 12 weeks after treatment completion 1, 4
• SVR12 corresponds to definitive cure in >99% of cases 1

Treatment Monitoring

Efficacy Monitoring

• Measure HCV RNA at baseline and at 12 weeks post-treatment (SVR12) to confirm cure 1
• Optional on-treatment monitoring at weeks 2-4 can assess adherence 1
• In high SVR rate pangenotypic regimens, checking SVR is dispensable except in patients at risk of reinfection or with poor adherence 1
• HCV core antigen can substitute for HCV RNA testing when molecular assays are unavailable 1

Safety Monitoring

• Monitor for drug-drug interactions with all concurrent medications, including over-the-counter and recreational drugs 1
• DAA regimens are generally well-tolerated with <1% discontinuation rates due to adverse events 1
• Renal function should be checked regularly in patients receiving sofosbuvir 1
• No dose adjustments are required for any recommended DAA regimens 1

Critical Pre-Treatment Assessment

• Test all patients for hepatitis B (HBsAg and anti-HBc) before initiating HCV treatment due to risk of HBV reactivation 5
• Assess liver disease severity to identify cirrhosis, as this affects treatment duration 1
• Determine HCV genotype when available, though pangenotypic regimens eliminate this requirement in most cases 2
• Screen for HIV coinfection in at-risk patients; same DAA regimens can be used with attention to antiretroviral drug interactions 1, 2

Special Populations

Recently Acquired Acute Hepatitis C

• Treat with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for 8 weeks 1
• Assess SVR at both 12 and 24 weeks post-treatment, as late relapses have been reported 1
• No indication for post-exposure prophylaxis without documented HCV transmission 1

Severe Renal Impairment/Dialysis

• Glecaprevir/pibrentasvir is preferred as it does not require dose adjustment in renal impairment 5
• Ledipasvir/sofosbuvir can be used in patients with end-stage renal disease on dialysis for 8-12 weeks 6

Pediatric Patients ≥3 Years

• Same treatment regimens and durations as adults 5, 6
• Weight-based dosing for children <45 kg using oral pellets 5

Post-Treatment Surveillance

• Patients with cirrhosis who achieve SVR must continue hepatocellular carcinoma surveillance with ultrasound every 6 months indefinitely 1, 4, 2
• HCV eradication reduces but does not eliminate HCC risk in cirrhotic patients 1
• Patients at risk of reinfection (active injection drug use, HIV-positive men who have sex with men) should be retested annually 3

Common Pitfalls to Avoid

• Do not delay treatment waiting for fibrosis assessment—all patients with confirmed active HCV should be treated regardless of fibrosis stage 1
• Do not use interferon-based regimens—all-oral DAA regimens have replaced interferon entirely 7, 8
• Do not stop interacting medications without checking alternatives—many drug interactions can be managed through temporary cessation, dose adjustment, or switching to non-interacting alternatives 1
• Do not forget HBV screening—HBV reactivation can cause fulminant hepatitis and death in coinfected patients 5