Treatment-Naive Genotype 2 With Compensated Cirrhosis

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

Treatment-Naive 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 8 weeks I, B
a For decompensated cirrhosis, please refer to the appropriate section.
b Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily. Please refer to the prescribing information.​


Recommended Regimens


The daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks was approved by the FDA for the treatment of genotype 2 infection in patients without cirrhosis or with compensated cirrhosis. ASTRAL-2 compared 12 weeks of sofosbuvir/velpatasvir to 12 weeks of sofosbuvir plus ribavirin in 266 treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis. The study showed superior efficacy of sofosbuvir/velpatasvir compared to sofosbuvir plus ribavirin (SVR12 99% vs 94%); (Foster, 2015a). ASTRAL-1 also included 104 genotype 2 treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis, all of whom achieved SVR12 (Feld, 2015).

Pooled analysis of all genotype 2 patients in ASTRAL-1 and ASTRAL-2 demonstrated 100% SVR12 in those with compensated cirrhosis (29/29) and 99% SVR12 in treatment-naive participants (194/195). Among patients with genotype 2 receiving sofosbuvir/velpatasvir, the presence of baseline NS5A or NS5B RASs was not associated with virologic failure (Asselah, 2018).

The POLARIS-2 phase 3 study randomized DAA-naive patients to 8 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) versus 12 weeks of sofosbuvir/velpatasvir. Fifty-three patients with genotype 2 were included in the sofosbuvir/velpatasvir arm and all achieved SVR12 (100%). This study confirms the high efficacy and safety of this 12-week regimen in patients with genotype 2 infection (Jacobson, 2017). A real-world, pooled analysis of 12 cohort studies demonstrated an SVR of 98.5% (266/270) among adults with genotype 2 infection and compensated cirrhosis who were treated with 12 weeks of sofosbuvir/velpatasvir (Mangia, 2020).


EXPEDITION-1 was a multicenter, open-label, single-arm, phase 3 trial that enrolled 146 treatment-naive or -experienced patients (interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon) with genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. Participants were treated with the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills for 12 weeks. Across all genotypes, 145/146 (99%) achieved SVR12 (Forns, 2017). EXPEDITION-1 included 31 treatment-naive and -experienced persons with genotype 2 infection and compensated cirrhosis; all achieved SVR12. Baseline NS5A RASs were detected (by next-generation sequencing using a 15% detection cutoff) in 40% of 133 tested participants. Baseline NS5A RASs had no effect on SVR rates among treatment-naive and -experienced patients with genotype 2 infection.

EXPEDITION-8 evaluated glecaprevir/pibrentasvir for a reduced duration of 8 weeks in 280 treatment-naive patients with compensated cirrhosis and genotype 1, 2 (n=26), 4, 5 or 6 infection. Patients with a prior history of decompensation, hepatocellular carcinoma, and HIV or HBV coinfection were excluded from this study. SVR12 was 99% with no virologic failures (Brown, 2018). Real-world data support the use of 8 weeks in cirrhotic patients (Flamm, 2020).

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Last update: 
October 24, 2022