Treatment of Active Hepatitis C Infection

Introduction to HCV Treatment

• The American Association for the Study of Liver Diseases recommends that all patients with confirmed active 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

Preferred First-Line Regimen

• Sofosbuvir/velpatasvir is the preferred pangenotypic option, administered as a single tablet (400mg/100mg) once daily for 12 weeks, achieving 98% sustained virological response (SVR) rates across all genotypes (1-6) regardless of treatment history 1, 3

Alternative First-Line Regimen

• Glecaprevir/pibrentasvir serves as an equally effective alternative with treatment duration stratified by cirrhosis status: 8 weeks for patients without cirrhosis 1, 2, 3
• Glecaprevir/pibrentasvir for 12 weeks for patients with compensated cirrhosis (Child-Pugh A) 1, 2, 3

Pre-Treatment Assessment Requirements

Genotype-Specific Considerations

• For genotype 1a, ledipasvir/sofosbuvir 90mg/400mg daily for 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis) is recommended 4, 5, 2
• For genotype 1b, ledipasvir/sofosbuvir 90mg/400mg daily for 12 weeks is recommended 5, 6, 2
• For genotype 3, sofosbuvir/velpatasvir for 12 weeks without ribavirin is recommended for treatment-naive patients without cirrhosis 7, 2

Treatment Modifications for Cirrhosis

• For compensated cirrhosis (Child-Pugh A), the same pangenotypic regimens as non-cirrhotic patients should be used, with glecaprevir/pibrentasvir duration extended to 12 weeks 1, 2
• For decompensated cirrhosis (Child-Pugh B or C), sofosbuvir/velpatasvir plus ribavirin for 12 weeks is recommended 2

Special Populations

• For HIV/HCV coinfection, the same HCV treatment regimens as HCV mono-infected patients should be used, with verification of antiretroviral drug interactions before prescribing 1, 3

Critical Drug-Drug Interactions

• Absolute contraindications include P-glycoprotein (P-gp) inducers, moderate-to-strong CYP3A4 inducers, efavirenz-containing antiretroviral regimens, and St. John's wort 1, 3

Monitoring Protocol

• During treatment, HCV RNA should be monitored at baseline, weeks 4 and 12, and at the end of treatment 1, 3
• Post-treatment, HCV RNA at 12 weeks (SVR12) is the primary measure of cure, achieved in >99% of patients who reach this endpoint 1, 3

Expected Outcomes

• With modern DAA regimens, expected outcomes include SVR rates exceeding 95% in most patient populations, improvement in liver histology, decreased risk of cirrhotic complications, reduced occurrence of hepatocellular carcinoma, improved survival rates, and resolution of extrahepatic manifestations 1