Purpose / DescriptionIn the ION-2 trial, investigators randomized 440 treatment-experienced patients with genotype 1 chronic hepatitis C infection to receive a 12- or 24-week treatment with fixed-dose combination ledipasvir-sofosbuvir, with or without ribavirin. Patients were considered treatment-experienced if they had not achieved an SVR with a previous regimen of peginterferon plus ribavirin, with or without an NS3/4A protease inhibitor. For the treatment experienced patients, 41 to 46% had a prior nonresponse (null responder). Patients were allowed to enroll if they had cirrhosis, but the number of patients with cirrhosis enrolled could not exceed 20% of the total enrolled. The SVR12 rate with 12 weeks of ledipasvir-sofosbuvir was 94% without ribavirin and 96% with ribavirin.  Both groups of patients who received 24 weeks of therapy had an SVR12 rate of 99%.  For patients with cirrhosis, the SVR rates were lower with 12 weeks of therapy (86% with ledipasvir-sofosbuvir and 82% with ledipasvir-sofosbuvir with ribavirin) compared with the respective 95% and 100% SVR rates with 12 weeks in patients who did not have cirrhosis.  The SVR rates were 99 to 100% in both treatment groups receiving 24 weeks of therapy, including those with cirrhosis. The investigators clearly established that ledipasvir-sofosbuvir is highly effective in treatment-experienced patients, even those who previously received an NS34A protease inhibitor. Treatment-experienced patients with cirrhosis may benefit by extending treatment duration from 12 to 24 weeks.