Treatment of Hepatitis C Genotype 2
For HCV genotype 2 infection, treat with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks without ribavirin, regardless of treatment history or cirrhosis status, achieving SVR rates of 99%. 1
First-Line Recommended Regimen
Sofosbuvir/velpatasvir is the preferred option based on the Phase III ASTRAL-2 trial demonstrating SVR12 in 99% (133/134) of genotype 2 patients, including those with compensated cirrhosis (14%) and treatment-experienced patients (14%). 1 This single-tablet, once-daily regimen is administered for 12 weeks without ribavirin for both treatment-naïve and treatment-experienced patients, with or without compensated cirrhosis. 1, 2
- In HIV-coinfected patients, this same regimen achieved 100% (11/11) SVR12 rates in the ASTRAL-5 trial. 1
- The deferred treatment study confirmed 100% (20/20) SVR12 in genotype 2 patients who received sofosbuvir-velpatasvir for 12 weeks. 3
Alternative Regimen
Sofosbuvir plus daclatasvir (400mg and 60mg daily, respectively) for 12 weeks without ribavirin is an acceptable alternative for both treatment-naïve and treatment-experienced patients with or without compensated cirrhosis. 1 This recommendation is based on daclatasvir's in vitro activity against genotype 2 and extrapolation from sofosbuvir/velpatasvir data, though direct clinical evidence is limited. 1
- In HIV-coinfected patients, daclatasvir dosing requires adjustment: 30mg daily with ritonavir- or cobicistat-boosted atazanavir or cobicistat-boosted elvitegravir, and 90mg daily with efavirenz. 1, 4
Treatment-Experienced Patients
For patients who failed prior peginterferon/ribavirin therapy:
- Without cirrhosis: Sofosbuvir/velpatasvir for 12 weeks achieves the same high SVR rates as treatment-naïve patients. 1
- With cirrhosis: The same 12-week regimen without ribavirin is recommended, maintaining 99% efficacy. 1
Older Sofosbuvir/Ribavirin Regimen (Now Superseded)
The combination of sofosbuvir 400mg plus weight-based ribavirin (1000mg if <75kg, 1200mg if ≥75kg) was previously used but has been replaced by more effective options. 1 Real-world data showed this regimen achieved only 83% SVR12 in intention-to-treat analysis and 89% per-protocol, significantly lower than the 99% with sofosbuvir/velpatasvir. 5
- Treatment-experienced patients without cirrhosis: 12 weeks achieved 93% SVR. 6
- Treatment-experienced patients with cirrhosis: Required extension to 16-24 weeks, achieving only 60-88% SVR depending on the study. 1, 6
This regimen is no longer recommended given superior alternatives. 2, 7
Critical Treatment Considerations
Duration
- 12 weeks is standard for all genotype 2 patients receiving sofosbuvir/velpatasvir, regardless of cirrhosis or treatment history. 1, 2
- Do not extend treatment duration beyond 12 weeks with modern DAA regimens—this does not improve outcomes and increases cost. 1
Ribavirin
- Ribavirin is not needed with sofosbuvir/velpatasvir or sofosbuvir/daclatasvir for genotype 2, even in cirrhotic or treatment-experienced patients. 1
- Adding ribavirin does not improve SVR rates and only increases adverse effects (anemia, fatigue). 1
Monitoring
- Measure HCV RNA at baseline, during treatment (weeks 4 and 12), at end of treatment, and 12 weeks post-treatment to confirm SVR12. 2, 7, 4
- For patients with cirrhosis, continue hepatocellular carcinoma surveillance with ultrasound every 6 months indefinitely, even after achieving SVR. 2, 7, 4
Common Pitfalls to Avoid
Do not use ledipasvir/sofosbuvir for genotype 2—ledipasvir lacks adequate activity against this genotype. 1 This is a genotype 1-specific regimen.
Do not extend treatment to 16 weeks in cirrhotic patients when using sofosbuvir/velpatasvir—the 12-week duration is equally effective. 1 The older recommendation for 16-week extension applied only to the inferior sofosbuvir/ribavirin regimen. 1
Verify drug-drug interactions before prescribing, particularly with antiretrovirals, proton pump inhibitors, and cardiac medications, as these can significantly reduce DAA concentrations. 2, 7
Do not defer treatment in patients with advanced fibrosis (F3-F4)—these patients have the most urgent need for viral eradication to prevent progression to decompensation. 7
Adverse Events
The most common adverse events with sofosbuvir/velpatasvir are headache, fatigue, nausea, and insomnia, occurring in <10% of patients. 8, 3 Discontinuation rates due to adverse events are extremely low (1%). 8, 3 The safety profile is comparable to placebo in controlled trials. 3