Treatment of Chronic Hepatitis C
For most patients with chronic hepatitis C, sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks is the preferred first-line treatment, regardless of genotype, treatment history, or presence of compensated cirrhosis. 1, 2, 3
First-Line Pangenotypic Regimens
The current standard of care centers on two highly effective pangenotypic options:
Primary Option: Sofosbuvir/Velpatasvir
- Administer sofosbuvir/velpatasvir (400mg/100mg) as a single tablet once daily for 12 weeks for treatment-naïve and treatment-experienced patients with or without compensated cirrhosis 4, 1
- This regimen achieves 95-98% sustained virologic response (SVR12) across all genotypes 1, 5, 6
- Effective in HIV/HCV coinfected patients with 92-95% SVR rates using the same 12-week duration 4, 2
- In Asian populations, demonstrated 97% overall SVR12, though lower efficacy (50%) was noted in genotype 3b cirrhotic patients 7
Alternative Option: Glecaprevir/Pibrentasvir
- For non-cirrhotic patients: administer glecaprevir/pibrentasvir (300mg/120mg) as three tablets once daily for 8 weeks 1, 2, 3, 8
- For compensated cirrhotic patients: extend treatment to 12 weeks 1, 2, 3, 8
- Achieves >95% SVR rates across genotypes 1-6 9
- Critical warning: Contraindicated in decompensated cirrhosis (Child-Pugh B or C) 2, 8
Genotype-Specific Considerations
Genotype 1 (Most Common in Western Countries)
- Ledipasvir/sofosbuvir for 12 weeks is an effective alternative 4
- Can shorten to 8 weeks in treatment-naïve, non-cirrhotic patients with baseline HCV RNA <6 million IU/mL 2, 3
- For cirrhotic patients, maintain 12-week duration without ribavirin 4
- All pangenotypic regimens achieve 95-98% SVR rates 1
Genotype 2
- Sofosbuvir plus ribavirin for 12 weeks (non-cirrhotic) or 16 weeks (cirrhotic) remains an option 2, 3
- Sofosbuvir/velpatasvir achieved 100% SVR in genotype 2 patients with advanced fibrosis or cirrhosis 10
Genotype 3 (Historically Difficult to Treat)
- Sofosbuvir/velpatasvir for 12 weeks is recommended for treatment-naïve non-cirrhotic patients 4, 2
- For treatment-experienced or cirrhotic patients: add ribavirin or extend to 24 weeks 4, 1, 2
- Daclatasvir plus sofosbuvir for 12 weeks (non-cirrhotic) or 24 weeks with ribavirin (cirrhotic) is an alternative 4, 3
- Important caveat: Genotype 3b with cirrhosis shows reduced efficacy (50% SVR) with standard sofosbuvir/velpatasvir 7
Genotype 4
- Multiple effective options: ledipasvir/sofosbuvir, elbasvir/grazoprevir, ombitasvir/paritaprevir/ritonavir plus ribavirin, or glecaprevir/pibrentasvir, all for 12 weeks 4, 1
- Treatment-naïve patients without cirrhosis: 8 weeks of glecaprevir/pibrentasvir 4
- Ombitasvir/paritaprevir/ritonavir plus ribavirin achieved 97-98% SVR in cirrhotic patients 4
Genotypes 5 and 6
- Sofosbuvir/velpatasvir for 12 weeks or ledipasvir/sofosbuvir for 12 weeks 4, 1
- Both achieved 100% SVR in clinical trials 10
Treatment-Experienced Patients
Prior NS5A Inhibitor Failure (Without Prior Protease Inhibitor)
- Glecaprevir/pibrentasvir for 16 weeks regardless of cirrhosis status 8
- This represents the most challenging retreatment scenario 9
Prior NS3/4A Protease Inhibitor Failure (Without Prior NS5A Inhibitor)
- Glecaprevir/pibrentasvir for 12 weeks regardless of cirrhosis status 8
Prior Peginterferon/Ribavirin/Sofosbuvir (No DAA Exposure)
- Genotypes 1,2,4,5,6: glecaprevir/pibrentasvir for 8 weeks (non-cirrhotic) or 12 weeks (cirrhotic) 8
- Genotype 3: glecaprevir/pibrentasvir for 16 weeks regardless of cirrhosis status 8
Special Populations
Decompensated Cirrhosis (Child-Pugh B or C)
- Ledipasvir/sofosbuvir plus ribavirin for 12 weeks 2
- Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2, 5, 6
- Never use glecaprevir/pibrentasvir in decompensated cirrhosis 2, 8
- SVR rates of 85-100% reported 5
HIV/HCV Coinfection
- Use the same regimens and durations as HCV monoinfection 4, 2
- Sofosbuvir/velpatasvir achieves 92-95% SVR rates 4, 2
- Critical: Perform comprehensive medication reconciliation to identify antiretroviral drug interactions 3
Chronic Kidney Disease and Dialysis
- Glecaprevir/pibrentasvir is safe and effective in patients with any stage of renal impairment, including dialysis 8, 9
- No dose adjustment required 8
- Avoid sofosbuvir-containing regimens in severe renal impairment (eGFR <30 mL/min) due to accumulation of metabolites 9
Pre-Treatment Assessment
Mandatory testing before initiating therapy:
- HCV genotype determination 1, 3
- HCV RNA viral load 1, 3
- Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) to assess for HBV coinfection 8
- Assessment for cirrhosis using FIB-4 score, transient elastography (FibroScan), or FibroTest 1, 3
- Comprehensive medication reconciliation to identify potential drug-drug interactions 1, 3
Monitoring During and After Treatment
- No routine laboratory monitoring required during treatment for most patients 3
- Measure HCV RNA at 12 weeks post-treatment (SVR12) to confirm virologic cure 1, 2, 3
- Undetectable HCV RNA at SVR12 defines virologic cure 1
- Obtain hepatic function panel after treatment to assess for normalization of liver enzymes 1, 3
Critical Warnings and Common Pitfalls
Hepatitis B Reactivation
- HBV reactivation has been reported in HCV/HBV coinfected patients receiving DAAs, with cases resulting in fulminant hepatitis, hepatic failure, and death 8
- Monitor HCV/HBV coinfected patients for hepatitis flare during and after HCV treatment 8
- Initiate HBV antiviral therapy as clinically indicated 8
Ribavirin Considerations
- When ribavirin is required, use weight-based dosing 1
- Reduce dose in renal impairment (CrCl ≤50 mL/min) 1
- Ribavirin is teratogenic and requires strict contraception 4
Resistance-Associated Substitutions (RAS)
- For genotype 1a with NS5A RAS, adding ribavirin improves SVR from 88% to 94% in cirrhotic patients 4
- Baseline NS5A RAS do not significantly impair SVR with sofosbuvir/velpatasvir 5, 6
- All genotype 3b patients have baseline NS5A RAS; consider this when treating cirrhotic genotype 3b patients 7