What is the recommended initial treatment approach for a patient with Hepatitis C Virus (HCV) positive status?

Initial Treatment Approach for HCV Positive Patients

For patients with newly diagnosed HCV infection, the recommended initial treatment approach is a direct-acting antiviral (DAA) regimen, specifically either glecaprevir/pibrentasvir for 8 weeks or sofosbuvir/velpatasvir for 12 weeks, depending on patient characteristics and comorbidities. 1

Pre-Treatment Assessment

Before initiating treatment, the following evaluations are essential:

1. HBV coinfection screening:

   • Test all patients for HBsAg and anti-HBc to rule out current or prior HBV infection 2, 3
   • HBV reactivation can occur during or after HCV treatment, potentially causing fulminant hepatitis

2. Fibrosis assessment:

   • Calculate FIB-4 score
   • Consider transient elastography (FibroScan), serum biomarkers, or imaging
   • Determine presence of cirrhosis (affects treatment duration and monitoring) 1

3. Cirrhosis evaluation:

   • Calculate Child-Pugh score for patients with suspected cirrhosis
   • Perform liver ultrasound to exclude HCC and subclinical ascites 1

4. Medication reconciliation:

   • Document all current medications including over-the-counter drugs and supplements
   • Assess for potential drug-drug interactions using AASLD/IDSA guidance or University of Liverpool interaction checker 1

Treatment Eligibility Assessment

Simplified Treatment Eligible Patients 1

• Adults with chronic HCV (any genotype)
• Treatment-naïve or treatment-experienced with compensated cirrhosis (Child-Pugh A)
• No evidence of decompensated liver disease

Patients NOT Eligible for Simplified Treatment 1

• Current or prior decompensated cirrhosis (Child-Pugh B or C)
• Prior hepatitis C treatment failure with DAAs
• End-stage renal disease (eGFR <30 mL/min/m²)
• HIV or HBsAg positive
• Current pregnancy
• Known or suspected hepatocellular carcinoma
• Prior liver transplantation

Recommended Treatment Regimens

First-line options (for simplified treatment eligible patients):

1. Glecaprevir (300 mg)/pibrentasvir (120 mg):

   • Dosing: Once daily with food
   • Duration: 8 weeks for non-cirrhotic patients; 12 weeks for compensated cirrhosis 1, 4
   • Advantages: Shorter treatment duration, high efficacy across genotypes

2. Sofosbuvir (400 mg)/velpatasvir (100 mg):

   • Dosing: Once daily with or without food
   • Duration: 12 weeks 1, 2
   • Advantages: Pangenotypic coverage, fewer drug interactions than glecaprevir/pibrentasvir

Treatment considerations:

• For genotype 3 with cirrhosis: Consider adding ribavirin to sofosbuvir/velpatasvir 1
• For decompensated cirrhosis: Use sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2
• For patients with prior NS5A inhibitor failure: Consider sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 5

Monitoring During Treatment

1. For most patients:

   • No routine laboratory monitoring required during treatment 1
   • Optional telehealth/in-person visit for support and symptom assessment

2. Special monitoring:

   • For patients on diabetes medications: Monitor for hypoglycemia 1
   • For patients on warfarin: Monitor INR for subtherapeutic anticoagulation 1

Post-Treatment Assessment

1. SVR assessment:

   • Check HCV RNA and hepatic function panel at 12 weeks post-treatment to confirm cure 1
   • SVR (sustained virologic response) = undetectable HCV RNA 12 weeks after treatment completion

2. Follow-up for treatment failure:

   • Refer to specialist for retreatment evaluation if SVR not achieved
   • For patients unable to be retreated, monitor disease progression every 6-12 months 1
   • Advise all patients to avoid excess alcohol use

Common Pitfalls to Avoid

1. Missing HBV coinfection: Always screen for HBV before starting treatment to prevent reactivation 2, 3

2. Overlooking drug interactions: DAAs have significant interaction potential, especially glecaprevir/pibrentasvir with cardiovascular medications

3. Inappropriate treatment duration: Treatment duration varies based on cirrhosis status and prior treatment history

4. Inadequate ribavirin dosing: When required, ribavirin should be dosed based on weight (1,000 mg for <75 kg, 1,200 mg for ≥75 kg) 6, 2

5. Missing post-treatment assessment: Failure to confirm SVR may result in unrecognized treatment failure

The treatment of HCV has evolved dramatically with highly effective DAA regimens that can achieve >95% cure rates with short-duration, well-tolerated therapy. Proper patient assessment, appropriate regimen selection, and post-treatment confirmation of cure are essential components of successful HCV management.