Daclatasvir/Sofosbuvir Improves Liver Parameters in HCV, Advanced Cirrhosis
SAN FRANCISCO, CA—Patients from the advanced cirrhosis cohort of the Phase 3 ALLY-1 study had high rates of sustained virologic response (SVR12) when treated with daclatasvir/sofosbuvir/ribavirin, as well as improved clinical and biochemical indicators of liver disease, investigators reported at The Liver Meeting® 2015.
In “multiple high-need patient populations with chronic HCV infection,” the “pangenotypic combination of daclatasvir and sofosbuvir, with or without ribavirin, has achieved SVR12 rates of 82% to 98%,” Robert J. Fontana, MD, University of Michigan Medical Center, Ann Arbor, MI, noted.
For example, in the open-label ALLY-1 study, “daclatasvir + sofosbuvir + ribavirin achieved SVR12 in 83% of patients with advanced cirrhosis and in 94% of those with post-liver transplant recurrence.”
In this analysis, he and his colleagues evaluated changes over time in liver disease parameters among patients from the advanced cirrhosis cohort of ALLY-1. The trial enrolled treatment-naive or treatment-experienced adults who had HCV infection of any genotype (GT).
Those in the advanced cirrhosis cohort (n=60) received 12 weeks of treatment with daclatasvir 60mg plus sofosbuvir 400mg once daily and ribavirin. Initially, sofosbuvir was administered at 600mg/day; however, the dose was adjusted for hemoglobin and creatinine clearance. The primary endpoint was HCV RNA <LLOQ (25 IU/mL) at post-treatment Week 12 in patients with GT1 infection.
A total of 60% of patients were treatment-experienced and 6 patients had hepatocellular carcinoma (HCC). Genotypes were as follows: GT1a, 57%; GT1b, 18%; GT2, 8%; GT3, 10%; and GT4, 7%. At baseline, Child-Pugh classifications were A, 20%; B, 53%; and C, 27%. MELD scores ranged from 8 to 27.
The primary endpoint, SVR12, was achieved by 11 patients (92%) with Child-Pugh A, 30 (94%) with B, and 9 (56%) with C. Four patients, all of whom had HCC, underwent transplantation during treatment and were excluded from analysis.
“During the 24 weeks between baseline and post-treatment Week 12, Child-Pugh scores, FibroTest scores, albumin levels, and total bilirubin levels all demonstrated consistent trends toward improvement, with no marked differences according to Child-Pugh class,” Dr. Fontana noted.
In addition, in 30 of 45 patients who achieved SVR12, MELD scores improved or remained stable. This was also observed in 6 (100%) patients with Child-Pugh C disease and 6 (60%) of those who did not attain SVR12.
Dr. Fontana concluded, "Further follow-up will provide additional information about longer-term improvements in liver disease status."