First-line treatment regimens for Gt 3 HCV now include sofosbuvir plus velpatasvir, glecaprevir plus pibrentasvir, and sofosbuvir plus daclatasvir with or without ribavirin. The other regimens available on the PBS — including sofosbuvir plus ribavirin, and sofosbuvir plus pegIFN plus ribavirin — can no longer be recommended as first-line therapy.
The combination of sofosbuvir plus velpatasvir is a safe and effective treatment for Gt 3 HCV (Sofosbuvir plus velpatasvir and Tables 3 and 4). The recommended treatment duration is 12 weeks for all patients. Cure rates > 95% were observed in clinical trials, including among people with cirrhosis.[35] Patients with Gt 3 HCV who have cirrhosis have been observed to have slightly lower rates of SVR (89%–93%). [35] For this group, consider adding ribavirin to the treatment regimen (Table 4).
The combination of glecaprevir plus pibrentasvir is a safe and effective treatment for Gt 3 HCV (Glecaprevir plus pibrentasvir and Table 3). The recommended treatment duration is 8 weeks for people with no cirrhosis and 12 weeks for people with cirrhosis. Cure rates > 95% were observed in clinical trials.[36]
Combination therapy with sofosbuvir and daclatasvir for 12 weeks in people with Gt 3 HCV infection and no cirrhosis is very effective, with SVR rates of 94%–97%. [56] Lower SVR rates of 58%–69% are observed in those with cirrhosis, regardless of treatment history. [56] Therefore, for people with Gt 3 HCV and cirrhosis, it is recommended that, if this regimen is selected, treatment be extended to 24 weeks. Evidence supporting treatment extension comes from a French multicentre compassionate access program, which reported an SVR rate of 86% in patients with Gt 3 HCV infection and cirrhosis who were treated for 24 weeks with sofosbuvir plus daclatasvir. [57]
Recent data suggest that sofosbuvir plus daclatasvir plus ribavirin for 12 weeks has similar efficacy in people with cirrhosis. The ALLY-3+ Study reported an overall SVR rate of 90% in people with advanced fibrosis or cirrhosis treated for 12 or 16 weeks with sofosbuvir plus daclatasvir plus ribavirin. [58] The SVR rate in the cirrhosis subgroup was 86%. SVR rates were similar with 12 or 16 weeks’ treatment duration. The combination of sofosbuvir plus daclatasvir plus ribavirin for 12 weeks’ duration is available on the PBS for the treatment of Gt 3 HCV in people with cirrhosis.
Treatment response rates for people with Gt 3 HCV, cirrhosis and decompensated liver disease remain suboptimal; in this population, the recommended treatment regimen is sofosbuvir plus daclatasvir plus ribavirin for 24 weeks (see treatment of decompensated liver disease).
Prescriptions for sofosbuvir plus daclatasvir have decreased since the introduction of sofosbuvir plus velpatasvir, which is a single-tablet, ribavirin-free, 12-week regimen for all patients with Gt 3 HCV. There may be certain clinical situations in which sofosbuvir plus daclatasvir would be the preferred regimen, including for patients with severe symptomatic reflux oesophagitis requiring high-dose proton pump inhibitor therapy, or for patients with decompensated cirrhosis who are intolerant of ribavirin and in whom 24-week treatment duration is planned (see treatment of decompensated liver disease).