What is the recommended treatment for Hepatitis C Virus (HCV) infection?

Treatment of Hepatitis C Virus (HCV) Infection

All patients with chronic HCV infection should be treated with a pangenotypic direct-acting antiviral (DAA) regimen, specifically sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status. 1, 2, 3

First-Line Treatment Regimens

Sofosbuvir/velpatasvir is the preferred pangenotypic regimen, achieving 98% SVR rates across all HCV genotypes (1-6), administered as a single tablet once daily for 12 weeks regardless of genotype. 1, 2, 4

Glecaprevir/pibrentasvir is an equally effective alternative, with treatment duration stratified by cirrhosis status:

• 8 weeks for patients without cirrhosis 1, 2
• 12 weeks for patients with compensated cirrhosis (Child-Pugh A) 1, 2

Both regimens are effective in treatment-naïve and treatment-experienced patients, including those who previously failed pegylated interferon and ribavirin. 3, 4

Treatment Modifications by Clinical Scenario

Compensated Cirrhosis (Child-Pugh A)

Use the same pangenotypic regimens as non-cirrhotic patients, with glecaprevir/pibrentasvir extended to 12 weeks. 1, 2

Decompensated Cirrhosis (Child-Pugh B or C)

Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks (1,000 mg daily if <75 kg; 1,200 mg daily if ≥75 kg, divided twice daily). 4

Liver Transplant Recipients

Sofosbuvir/velpatasvir plus ribavirin for 12 weeks, applicable both pre- and post-transplant. 1

HIV/HCV Coinfection

The same HCV treatment regimens can be used in HIV-coinfected patients as in HCV mono-infected patients, with identical virological outcomes. 5, 3 Critical caveat: Dose adjustments may be required based on antiretroviral drug interactions—daclatasvir requires adjustment to 30 mg daily with atazanavir/ritonavir and 90 mg daily with efavirenz. 5

Pre-Treatment Assessment Requirements

Before initiating DAA therapy, mandatory testing includes:

• HCV RNA quantitative testing 1
• HCV genotype and subtype determination 1, 2
• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) to identify HBV coinfection risk 4
• Fibrosis staging using noninvasive methods or liver biopsy 1, 2
• Comprehensive drug-drug interaction screening 1, 2

Treatment Prioritization

Immediate treatment priority should be given to:

• Patients with advanced fibrosis (≥F3) or any cirrhosis 1, 2
• Pre- and post-liver transplant patients 1
• Patients with severe extrahepatic manifestations 1
• Patients with hepatocellular carcinoma 1

Critical Drug-Drug Interactions

Absolute contraindications: P-glycoprotein (P-gp) inducers and moderate-to-strong CYP inducers, which significantly decrease DAA concentrations and reduce efficacy. 1, 2 Always verify interactions before prescribing, particularly with antiretrovirals, cardiac medications (especially amiodarone), and acid-suppressing agents. 2, 6

Monitoring Protocol

HCV RNA monitoring schedule:

• Baseline 1, 2
• Weeks 4 and 12 during treatment 1, 2
• End of treatment 1, 2
• 12 weeks post-treatment (SVR12) 1, 2

SVR12 (undetectable HCV RNA 12 weeks after treatment completion) is the primary measure of cure, achieved in >99% of patients who reach this endpoint. 1, 2 This represents viral eradication and is associated with resolution of liver disease in non-cirrhotic patients. 5

Treatment Goals and Expected Outcomes

The primary goal is HCV eradication, preventing:

• Cirrhosis complications 1
• Hepatocellular carcinoma 1
• Extrahepatic manifestations 1
• Death 1

Expected outcomes with modern DAA regimens:

• SVR rates exceeding 95% in most patient populations 1, 7
• Improvement in liver histology 1
• Decreased risk of cirrhotic complications 1
• Reduced occurrence of hepatocellular carcinoma 1
• Improved survival rates 1

Retreatment After DAA Failure

For the rare patients who fail initial DAA therapy:

If failed sofosbuvir alone or sofosbuvir plus ribavirin: Retreat with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir with ribavirin for 12 weeks (F0-F2) or 24 weeks (F3-F4). 5

If failed NS5A inhibitor-containing regimen (ledipasvir, velpatasvir, daclatasvir, ombitasvir, elbasvir): Use combination of sofosbuvir with a protease inhibitor (grazoprevir/elbasvir or simeprevir) plus ribavirin for 12 weeks (genotype 1b or 4 without cirrhosis) or 24 weeks (genotype 1a or cirrhosis). 5, 8

Critical Pitfalls to Avoid

Do not defer treatment in patients with advanced fibrosis (F3-F4), as these patients have the most urgent need and greatest short-term benefit from viral eradication. 2

Do not use genotype 1a-specific regimens without confirming subtype—if genotype 1 cannot be subtyped, treat as 1a. 2

Continue HCC surveillance with ultrasound every 6 months indefinitely in cirrhotic patients, even after achieving SVR, as HCC risk is reduced but not eliminated. 1, 2, 3

Warn patients about serious symptomatic bradycardia when coadministering with amiodarone—advise immediate medical evaluation for near-fainting, dizziness, weakness, or chest pain. 6