Purpose / DescriptionIn this phase 2, open label trial, 337 patients with HCV genotype 1 or 4 and advanced liver disease were randomized to receive either a 12-week or 24-week course of ledipasvir-sofosbuvir plus ribavirin. The study included two cohorts: the cohort A (pretransplantation) arm of the study enrolled patients with cirrhosis and moderate to severe hepatic impairment; cohort B consisted of patients who were post liver transplantation. Patients were also stratified based on no cirrhosis, Child-Turcotte-Pugh (CTP) class A, B or Class C, and fibrosing cholestatic hepatitis. In the cohort A (pre-transplant) group, the SVR12 rate was 87% in the 12-week arm and 89% in the 24-week arm. In the cohort B (post-transplant) group, SVR12 results with combined 12 and 24 week data show clearly better in patients with less advanced liver disease: 96% in CTP A versus 87% in CTP  B versus 67% in CTP C.  The results were similar with either 12- or 24 weeks of treatment except for patients with CTP C: nine post-transplant patients with CTP C received therapy and SVR rates 60% with 12 weeks of therapy and 75% with 24 weeks. The treatment was well-tolerated and there were few treatment-related adverse events. The patients with virologic response had significant improvement in liver function, including improvements in bilirubin, albumin, Modified End Stage Liver Disease (MELD) scores, and Child-Turcotte-Pugh scores. These results are very promising for the treatment of patients with advanced liver disease, including post-transplantation patients, and it appears that a 12-week course is equivalent to the 24-week course, except perhaps with patients who have CTP C liver disease.