An All-Oral Regimen for Hepatitis C Succeeds in 68% of Difficult-to-Treat Patients

Sixty-eight percent of patients with preexisting liver damage and other poor prognostic factors treated with a combination of sofosbuvir and ribavirin attained functional cure of hepatitis C, as measured by sustained viral response 24 weeks after the end of treatment.

On August 28, 2013, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) published results of a trial evaluating the efficacy of an all-oral treatment for hepatitis C. Sixty treatment-naive patients with genotype 1 hepatitis C virus (HCV) infection received treatment for 24 weeks. As in other trials of hepatitis C treatments, the primary endpoint was the percentage of patients experiencing sustained viral response 24 weeks after the end of treatment (SVR₂₄). In patients who achieve SVR₂₄, the chance of relapse is lower than 1%, so attainment of SVR₂₄ constitutes a functional cure of hepatitis C. Patients received 2 oral medications: sofosbuvir, a polymerase inhibitor, and the antiviral ribavirin.

At the start of the study, a liver biopsy of each patient confirmed that each patient had liver fibrosis indicating a chronic, untreated hepatitis C infection. Investigators screened 79 patients, excluding patients with HIV coinfection, patients with low hemoglobin levels, patients with low platelet counts, and patients with HCV genotypes other than type 1, resulting in 60 qualified participants. Two-thirds of participants were of African descent, two-thirds were men, and just under half (48%) were obese. Almost one-fourth (23%) had advanced liver disease, and more than half (62%) had high levels of HCV (>800,000 copies/mL).

Each of these 60 patients’ level of liver fibrosis was assessed using the Knodell histology activity index (HAI). Because investigators were unsure of the safety of these medications in patients with liver fibrosis, investigators selected 10 patients who had low levels of liver fibrosis to receive medication in the first part of the trial. These 10 patients received low-dose sofosbuvir (400 mg daily) with weight-based dosing of ribavirin (1000 mg daily or 1200 mg, depending on weight). Results, published in January 2013, showed that all 10 achieved SVR₂₄.

After the promising results of this early phase, the remaining 50 patients received medication—even patients with compensated cirrhosis. Investigators assigned each of the 50 patients randomly to either group A or group B. The 25 patients in group A received low-dose sofosbuvir (400 mg daily) with weight-based dosing of ribavirin (1000 mg daily or 1200 mg, depending on weight). The other 25 patients, assigned to group B, received a high dose of sofosbuvir (600 mg daily) with low-dose ribavirin (600 mg daily). By the fourth week of treatment, investigators found that levels of HCV were suppressed in 24 of 25 patients in each group. Despite this, 24 weeks after therapy was complete, 7 patients in group A (400 mg sofosbuvir/weight-based ribavirin) and 10 patients in group B (400 mg sofosbuvir/600 mg ribavirin) failed to achieve SVR₂₄.

Using an intent-to-treat analysis, 68% (95% CI: 46% to 85%) of patients in group A and 48% (95% CI: 28% to 69%) of patients in group B achieved SVR₂₄. The difference in SVR₂₄ was not statistically significant, with a 20% probability that the lower rate of SVR₂₄ in group B occurred due to chance.

In a per-protocol analysis, investigators analyzed data by including only patients who received medication for at least 8 weeks, which amounted to 24 of 25 patients in group A and 22 of 25 patients in group B. In this analysis, 71% (95% CI: 49% to 87%) of patients in group A and 55% (95% CI: 32% to 76%) of patients in group B achieved SVR₂₄. Again, the difference between groups was not statistically significant.

Prior results with 12 weeks of sofosbuvir and ribavirin treatments in less difficult-to-treat patients have shown an 84% (95% CI: 64% to 96%) rate of SVR₂₄ in patients with type 1 HCV. A group of 9 patients with type 2 and 3 HCV showed a 100% SVR₂₄ rate following a 12-week course of sofosbuvir and ribavirin. The 68% cure rate observed in this trial shows that sofosbuvir and ribavirin retains good efficacy in a group of patients who have not responded well to treatment in the past—patients with liver fibrosis and compensated cirrhosis.