What is the recommended treatment for a patient with a positive Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) result?

Treatment for Patients with Positive HCV PCR Results

Direct-acting antiviral (DAA) therapy is the recommended first-line treatment for all patients with a positive Hepatitis C Virus (HCV) PCR result, with regimen selection based on viral genotype, liver disease severity, and comorbidities. 1

Initial Assessment

Before starting treatment, the following assessments are essential:

• HCV genotype determination (1-6)
• Liver fibrosis assessment (non-invasive methods preferred)
• Testing for HBV coinfection (HBsAg and anti-HBc) 2
• Baseline HCV viral load
• Assessment of liver function (Child-Pugh score if cirrhotic)
• Evaluation of renal function
• Review of current medications for potential drug interactions

Treatment Regimens by Patient Population

For Non-Cirrhotic Patients or Compensated Cirrhosis (Child-Pugh A)

• Pangenotypic regimen (all genotypes 1-6): Sofosbuvir/velpatasvir for 12 weeks 2
• Genotype-specific options:
  • Genotype 1: Sofosbuvir/ledipasvir, glecaprevir/pibrentasvir, or elbasvir/grazoprevir
  • Genotype 2-3: Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir
  • Genotype 4-6: Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir

For Decompensated Cirrhosis (Child-Pugh B or C)

• All genotypes: Sofosbuvir/velpatasvir + ribavirin for 12 weeks 2
• Ribavirin dosing: 1,000 mg/day for patients <75 kg and 1,200 mg/day for patients ≥75 kg (divided twice daily)

Special Populations

HCV/HIV Coinfection

• Same DAA regimens as HCV monoinfection
• Careful assessment of antiretroviral drug interactions

HCV/HBV Coinfection

• Test all patients for HBV (HBsAg and anti-HBc) before starting treatment 2
• Monitor for HBV reactivation during and after HCV treatment
• Consider concurrent HBV treatment if indicated

Patients with Renal Impairment

• No dosage adjustment of sofosbuvir/velpatasvir needed for any degree of renal impairment 2
• For severe renal impairment, glecaprevir/pibrentasvir may be preferred

Post-Liver Transplant

• Sofosbuvir/velpatasvir for 12 weeks for non-cirrhotic or compensated cirrhosis 1

Monitoring During Treatment

• Assess adherence at each visit
• Monitor for adverse effects
• For patients on ribavirin: CBC at weeks 2 and 4, then monthly
• For patients with cirrhosis: liver function tests at weeks 2,4,8, and 12
• For HBV/HCV coinfected patients: monitor for HBV reactivation 2

Post-Treatment Follow-up

• Check HCV RNA 12 weeks after completing therapy to confirm SVR (cure)
• Patients with cirrhosis require continued HCC surveillance every 6 months even after achieving SVR 1
• Counsel patients on risk reduction to prevent reinfection

Important Considerations and Pitfalls

1. Avoid older treatment regimens: Pegylated interferon and ribavirin alone or with first-generation protease inhibitors (telaprevir, boceprevir) are no longer recommended due to lower efficacy and higher toxicity 1

2. Drug interactions: Many DAAs interact with common medications. Always check for interactions before starting therapy 1

3. HBV reactivation risk: HBV can reactivate during or after HCV treatment, potentially causing severe hepatitis or liver failure 2

4. Amiodarone warning: Coadministration of amiodarone with sofosbuvir-containing regimens may cause serious symptomatic bradycardia 2

5. Alcohol consumption: Advise patients to abstain from alcohol during treatment 1

6. Adherence importance: Emphasize the importance of medication adherence to achieve cure and prevent resistance 1

Modern DAA therapy has transformed HCV treatment with cure rates exceeding 95% in most patient populations, including those previously difficult to treat 3. The goal of therapy is to achieve sustained virological response (SVR), defined as undetectable HCV RNA 12 weeks after completing treatment, which is associated with resolution of liver disease in non-cirrhotic patients and reduced risk of complications in cirrhotic patients 1.