Hepatitis C Management
First-Line Treatment Recommendation
For all patients with confirmed chronic hepatitis C infection, initiate treatment with a pangenotypic direct-acting antiviral (DAA) regimen: either sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks OR glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status. 1, 2, 3
Treatment Selection Algorithm
Standard First-Line Options (All Genotypes)
Sofosbuvir/velpatasvir is the preferred pangenotypic regimen with 98% SVR rates across all genotypes 1, 2:
- Dosing: Single tablet (400mg/100mg) once daily for 12 weeks 3
- Advantages: Works for all genotypes, simple dosing, minimal drug interactions 1
Glecaprevir/pibrentasvir is an equally effective alternative 1, 3:
- Without cirrhosis: 8 weeks of treatment 1, 3
- With compensated cirrhosis (Child-Pugh A): Extend to 12 weeks 1, 3
- Dosing: 3 tablets once daily with food 3
Treatment Modifications by Clinical Scenario
Patients with Compensated Cirrhosis (Child-Pugh A)
- Use the same pangenotypic regimens as non-cirrhotic patients 1
- Extend glecaprevir/pibrentasvir duration to 12 weeks 1, 3
- Sofosbuvir/velpatasvir remains 12 weeks 1
Patients with Decompensated Cirrhosis (Child-Pugh B or C)
- Sofosbuvir/velpatasvir PLUS ribavirin for 12 weeks 2, 3, 4
- Ribavirin starting dose: 600mg daily, titrate up to weight-based dosing (1000mg if <75kg, 1200mg if ≥75kg) in divided doses 4
Liver Transplant Recipients (Genotype 1 or 4)
- Sofosbuvir/velpatasvir PLUS ribavirin for 12 weeks 4
- Applies to both pre- and post-transplant settings 5
- Treatment should be prioritized in transplant candidates and recipients 5
Treatment-Experienced Patients with Cirrhosis (Genotype 1)
- Sofosbuvir/velpatasvir for 24 weeks (without ribavirin) 4
- Alternative: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 4
Patients with Severe Renal Impairment (GFR <30 mL/min or ESRD)
- Glecaprevir/pibrentasvir is preferred as sofosbuvir is contraindicated in severe renal impairment 5
- Ledipasvir/sofosbuvir can be used in ESRD patients on dialysis for 8-12 weeks 4
Pre-Treatment Assessment Requirements
Mandatory Testing Before Initiating DAAs
HBV screening is critical - test ALL patients for HBsAg and anti-HBc before starting treatment 4, 6:
- HBV reactivation has been reported during DAA therapy, with cases resulting in fulminant hepatitis and death 4, 6
- Monitor HCV/HBV coinfected patients during and after treatment 4, 6
Additional baseline assessments 1, 3:
- HCV RNA quantitative testing 3
- HCV genotype and subtype determination (genotype 1a vs 1b affects some treatment decisions) 1
- Fibrosis staging using noninvasive methods or biopsy to determine treatment urgency 1
- Comprehensive drug-drug interaction screening with ALL concurrent medications 3
Treatment Prioritization
Immediate treatment priority should be given to 5:
- Patients with advanced fibrosis (≥F3) or any cirrhosis (compensated or decompensated) 5
- Pre- and post-liver transplant patients 5
- Patients with severe extrahepatic manifestations (cryoglobulinemia, glomerulonephritis) 5
- Patients with hepatocellular carcinoma (HCV eradication reduces HCC recurrence) 5
Critical Drug-Drug Interactions
Absolute contraindications - do NOT use DAAs with 1:
- P-glycoprotein (P-gp) inducers
- Moderate-to-strong CYP inducers (significantly decrease DAA concentrations and reduce efficacy)
Common problematic medications 1:
- Antiretrovirals (require careful dose adjustments)
- Cardiac medications
- Acid-suppressing agents
- First-generation anticonvulsants (carbamazepine, phenytoin, phenobarbital) - though small case series suggest SVR may still be achievable, avoidance is strongly recommended 7
Monitoring Protocol
During Treatment
- HCV RNA levels: Baseline, weeks 4 and 12 during treatment, end of treatment, and 12 weeks post-treatment 1, 2, 3
Definition of Cure
- SVR12: Undetectable HCV RNA 12 weeks after treatment completion defines cure in >99% of patients 5, 3
Post-SVR Surveillance
For patients with cirrhosis who achieve SVR 1, 2:
- Continue HCC surveillance with ultrasound every 6 months indefinitely
- Risk of HCC is significantly reduced but not eliminated 1, 2
Treatment Goals and Expected Outcomes
Primary goal: Eradicate HCV to prevent cirrhosis complications, hepatocellular carcinoma, extrahepatic manifestations, and death 5
Expected outcomes with modern DAA regimens 3:
- SVR rates exceed 95% in most patient populations 3, 8
- Improvement in liver histology 5
- Decreased risk of cirrhotic complications 5
- Reduced occurrence of hepatocellular carcinoma 5
- Improved survival rates 5
- Resolution of extrahepatic manifestations 5
Common Pitfalls to Avoid
Do not defer treatment in patients with advanced fibrosis (F3-F4) - these patients have the most urgent need and greatest short-term benefit from viral eradication 1
For genotype 1 patients: Do not use genotype 1a-specific regimens without confirming subtype; if genotype 1 cannot be subtyped, treat as 1a 1
Always verify drug-drug interactions before prescribing - this is a critical step that cannot be skipped 1
For treatment failures (particularly NS5A inhibitor failures): Resistance-associated substitutions (RAS) develop in most patients who fail treatment 9. NS5A variants persist for >2 years, while NS3-4A variants disappear gradually 9. Re-treatment requires sofosbuvir backbone plus a drug from a different class for 24 weeks, with weight-based ribavirin added unless contraindicated 9