What is the recommended treatment for a patient with a positive Hepatitis C Virus (HCV) antibody test and significant viral load as indicated by Reverse Transcription Polymerase Chain Reaction (RT-PCR)?

Treatment for Hepatitis C Virus with Positive Antibody and Quantifiable Viral Load

Direct-acting antiviral (DAA) therapy is recommended for all adults with chronic HCV infection confirmed by positive antibody test and detectable HCV RNA by PCR, regardless of liver disease severity. 1

Diagnostic Confirmation

Before initiating treatment, the following diagnostic steps should be completed:

1. Confirm active infection: A positive HCV antibody test with detectable HCV RNA by PCR confirms current infection requiring treatment 1

2. Baseline testing:

   • HCV genotype determination (to guide treatment selection)
   • Baseline HCV RNA quantification
   • Assessment of liver disease severity (fibrosis/cirrhosis)
   • Screening for HBV (HBsAg) and HIV coinfection 1

Treatment Algorithm

Step 1: Assess for Simplified Treatment Eligibility

Patients are eligible for simplified treatment if they have:

• No prior HCV treatment
• No decompensated cirrhosis
• No HIV or HBsAg positivity
• No pregnancy
• No known hepatocellular carcinoma
• No prior liver transplantation 2

Step 2: Select Appropriate DAA Regimen

For patients eligible for simplified treatment:

• Without cirrhosis:

  • Glecaprevir/pibrentasvir for 8 weeks, OR
  • Sofosbuvir/velpatasvir for 12 weeks 2

• With compensated cirrhosis:

  • Glecaprevir/pibrentasvir for 12 weeks, OR
  • Sofosbuvir/velpatasvir for 12 weeks 2

For patients requiring genotype-specific treatment:

• Genotype 1:

  • Sofosbuvir/ledipasvir for 12 weeks (8 weeks may be considered in treatment-naïve patients without cirrhosis and HCV RNA <6 million IU/mL) 3
  • Glecaprevir/pibrentasvir for 8-12 weeks
  • Sofosbuvir/velpatasvir for 12 weeks

• Genotypes 2-6:

  • Glecaprevir/pibrentasvir for 8-12 weeks
  • Sofosbuvir/velpatasvir for 12 weeks

Step 3: Medication Reconciliation

Perform medication reconciliation to identify potential drug-drug interactions with DAAs, documenting all current medications including over-the-counter drugs and supplements 2

Monitoring During Treatment

1. Adherence assessment at each visit
2. Laboratory monitoring:
   • Complete blood count, hepatic function panel, and renal function tests at 4 weeks and as clinically indicated
   • HCV RNA testing is generally not needed during treatment with current DAA regimens 4
   • Patients on warfarin require INR monitoring 2

Post-Treatment Follow-up

1. HCV RNA testing at 12 weeks post-treatment to confirm sustained virologic response (SVR12)
2. For patients with cirrhosis: Continue hepatocellular carcinoma surveillance with ultrasound every 6 months 2
3. For patients with ongoing risk factors: Education about prevention of reinfection and periodic HCV RNA testing 1, 2

Special Considerations

Patients with Cirrhosis

• Patients with compensated cirrhosis can be treated with standard DAA regimens but may require longer duration of therapy 2
• Patients with decompensated cirrhosis should be referred to specialists with experience in managing advanced liver disease 1

HBV/HIV Coinfection

• Screen all patients for HBV and HIV before initiating HCV treatment 1
• Patients with HBsAg positivity require monitoring for HBV reactivation during HCV treatment 1
• HIV-coinfected patients may require adjustment of antiretroviral therapy to avoid drug interactions with DAAs 5

Treatment Efficacy and Outcomes

Current DAA regimens achieve SVR rates exceeding 95% in most patient populations, significantly reducing the risk of liver-related morbidity and mortality 1. Successful HCV treatment results in:

• Reduced rates of all-cause mortality
• Reduced progression to cirrhosis
• Reduced risk of hepatic decompensation and hepatocellular carcinoma
• Improvement in extrahepatic manifestations of HCV 1

Common Pitfalls to Avoid

1. Failing to screen for HBV coinfection - HBV reactivation can occur during DAA therapy
2. Overlooking drug-drug interactions - Many medications interact with DAAs
3. Unnecessarily delaying treatment - Early treatment prevents progression of liver disease
4. Inadequate post-treatment follow-up for patients with cirrhosis - They remain at risk for hepatocellular carcinoma despite SVR

The availability of highly effective, well-tolerated DAA regimens has revolutionized HCV treatment, making cure possible for the vast majority of patients with chronic HCV infection. Early identification and prompt treatment initiation are crucial for improving long-term outcomes and preventing complications.