Michael P Curry1, Jacqueline G O'Leary, Natalie Bzowej, Andrew J Muir, Kevin M Korenblat, Jonathan M Fenkel, K Rajender Reddy, Eric Lawitz, Steven L Flamm, Thomas Schiano, Lewis Teperman, Robert Fontana, Eugene Schiff, Michael Fried, Brian Doehle, Di An, John McNally, Anu Osinusi, Diana M Brainard, John G McHutchison, Robert S Brown, Michael Charlton. 1. From the Beth Israel Deaconess Medical Center, Boston (M.P.C.); Baylor University Medical Center, Dallas (J.G.O.), and Texas Liver Institute, University of Texas Health Science Center, San Antonio (E.L.) - both in Texas; Ochsner Medical Center, New Orleans (N.B.); Duke University, Durham (A.J.M.), and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (M.F.) - both in North Carolina; Washington University School of Medicine, St. Louis (K.M.K.); Thomas Jefferson University (J.M.F.) and University of Pennsylvania School of Medicine (K.R.R.) - both in Philadelphia; Northwestern University, Chicago (S.L.F.); Mount Sinai Hospital (T.S.), New York University School of Medicine (L.T.), and Weill Cornell Medical College (R.S.B.) - all in New York; University of Michigan, Ann Arbor (R.F.); University of Miami, Miami (E.S.); Gilead Sciences, Foster City, CA (B.D., D.A., J.M., A.O., D.M.B., J.G.M.); and Intermountain Medical Center, Salt Lake City (M.C.).
Abstract
BACKGROUND: As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS: We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS: Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.).
BACKGROUND: As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS: We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS: Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.).
Authors: David Goldberg; Ivo C Ditah; Kia Saeian; Mona Lalehzari; Andrew Aronsohn; Emmanuel C Gorospe; Michael Charlton Journal: Gastroenterology Date: 2017-01-11 Impact factor: 22.682
Authors: Sabrina A Assoumou; Shayla Nolen; Liesl Hagan; Jianing Wang; Golnaz Eftekhari Yazdi; William W Thompson; Kenneth H Mayer; Jon Puro; Lin Zhu; Joshua A Salomon; Benjamin P Linas Journal: Am J Med Date: 2020-06-27 Impact factor: 4.965
Authors: Josh Levitsky; David Goldberg; Abigail R Smith; Sarah A Mansfield; Brenda W Gillespie; Robert M Merion; Anna S F Lok; Gary Levy; Laura Kulik; Michael Abecassis; Abraham Shaked Journal: Clin Gastroenterol Hepatol Date: 2016-08-25 Impact factor: 11.382