Peginterferon/Ribavirin-Experienced, Genotype 2 Patients With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for:

Peginterferon/Ribavirin-Experienced, Genotype 2 Patients With Compensated Cirrhosisa

Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, B
Daily daclatasvir (60 mg)c plus sofosbuvir (400 mg) 16 to 24 weeks IIa, B
a For decompensated cirrhosis, please refer to the appropriate section.
​b This is a 3-tablet coformulation. Please refer to the prescribing information.
c The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.


Recommended Regimens


In the randomized, open-label ASTRAL-2 study, genotype 2-infected patients were treated with 12 weeks of the daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) or sofosbuvir plus ribavirin (Foster, 2015a). Of the 266 participants, a minority (15%) had a history of previous peginterferon/ribavirin treatment failure and a similar proportion (14%) had compensated cirrhosis. Overall, the combination of sofosbuvir/velpatasvir yielded a statistically significant superior SVR12 rate of 99% vs 94% for sofosbuvir plus ribavirin. The only treatment failure in the sofosbuvir/velpatasvir arm was a patient who withdrew from the study after a single day due to side effects (anxiety). In contrast, there were 6 virologic failures in the sofosbuvir plus ribavirin arm. Fatigue and anemia were more commonly reported in patients receiving sofosbuvir plus ribavirin.

The phase 3 POLARIS-2 study randomized patients to 8 weeks of sofosbuvir/velpatasvir/voxilaprevir or 12 weeks of sofosbuvir/velpatasvir. Fifty-three genotype 2-infected patients were included in the sofosbuvir/velpatasvir arm and all achieved SVR (100%, 53/53) (Jacobson, 2017). This study confirms the high efficacy and safety of this 12-week regimen in patients with genotype 2 infection, including those with a past peginterferon/ribavirin treatment failure and patients with compensated cirrhosis.

Considering the high SVR12 rate and fewer side effects with sofosbuvir/velpatasvir, regimens with peginterferon and/or ribavirin are no longer recommended for genotype 2 infection.


The phase 3, single arm, open-label EXPEDITION-1 study investigated the safety and efficacy of a 12-week course of the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills in patients with genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis (Forns, 2017). Treatment-naive and -experienced patients (interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon) were included in the trial. Overall, only 25% (n=36) of patients were treatment experienced. The SVR12 in the genotype 2-infected patients was 100% (31/31). Overall, 91% percent (133/146) of patients had a Child-Pugh score of 5, and 9% (13/146) had a Child-Pugh score of 6. Twenty percent of patients had a platelet count <100 x 109/L and all but 1 participant had a normal albumin level. In this patient population with compensated cirrhosis, the regimen was safe and well tolerated. There were 11 serious adverse events; none were DAA-related and no adverse events led to discontinuation of the study drugs. This is a safe and highly efficacious 12-week regimen in patients with well-compensated cirrhosis.

Alternative Regimen

Daclatasvir + Sofosbuvir

Daclatasvir (60 mg) plus sofosbuvir (400 mg) for 12 weeks to 24 weeks has been shown to have efficacy in genotype 2 infection. However, available data in patients previously treated with peginterferon/ribavirin are very limited (Wyles, 2015); (Sulkowski, 2014a). For patients who require treatment and are unable to access sofosbuvir/velpatasvir, treatment with daclatasvir/sofosbuvir for 12 weeks is an alternative regimen with consideration of extension of therapy to 24 weeks in more difficult-to-treat patients, such as those with cirrhosis.

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Last update: 
September 21, 2017