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Abstract Details
Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients with Advanced Liver Disease
Author information
1Intermountain Medical Center, Salt Lake City, UT. Electronic address: michael.charlton@imail.org.
2University of Colorado Denver, Aurora, CO.
3Northwestern Feinberg School of Medicine, Chicago, IL.
4Georgetown University, Washington, DC.
5University of Washington/Harborview Medical Center, Seattle, WA.
6Columbia University Medical Center/ New York Presbyterian, New York, NY.
7University of North Carolina at Chapel Hill / UNC School of Medicine, Chapel Hill, NC.
8University of California, San Francisco, CA.
9Baylor University Medical Center, Dallas, TX.
10Mayo Clinic Arizona, Phoenix, AZ.
11University of California, San Diego, CA.
12University of Miami, Miami, FL.
13Johns Hopkins University, Lutherville, MD.
14University of Kansas Medical Center Research Institute, Kansas City, KS.
15Mayo Clinic, Rochester, MN.
16Henry Ford Health System, Detroit, MI.
17Indiana University School of Medicine, Indianapolis, IN.
18Mayo Clinic Jacksonville, FL.
19Washington University, Saint Louis, MO.
20Duke University, Durham, NC.
21New York University School of Medicine, New York, NY.
22University of Michigan, Ann Arbor, MI.
23Gilead Sciences, Inc., Foster City, CA.
24University of Pennsylvania School of Medicine, Philadelphia, PA.
25Beth Israel Deaconess Medical Center, Boston, MA. Electronic address: nafdhal@bidmc.harvard.edu.
Abstract
BACKGROUND & AIMS:
There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease.
METHODS:
In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were randomly assigned (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12).
RESULTS:
We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (non-transplant), SVR12 was achieved by 86%-89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%-98% of patients without cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation.
CONCLUSION:
The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation.