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Gastroenterology. 2015 Sep;149(3):649-59. doi: 10.1053/j.gastro.2015.05.010. Epub 2015 May 15.

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.

Author information

1
Division of Hepatology and Liver Transplantation, Intermountain Medical Center, Salt Lake City, Utah. Electronic address: michael.charlton@imail.org.
2
Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado.
3
Division of Gastroenterology and Hepatology, Northwestern Feinberg School of Medicine, Chicago, Illinois.
4
Division of Infectious Diseases, Georgetown University, Washington, District of Columbia.
5
Division of Gastroenterology and Hepatology, University of Washington/Harborview Medical Center, Seattle, Washington.
6
Division of Digestive and Liver Diseases, Columbia University Medical Center/New York Presbyterian, New York, New York.
7
Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill/University of North Carolina School of Medicine, Chapel Hill, North Carolina.
8
Division of Gastroenterology and Hepatology, University of California, San Francisco, California.
9
Division of Gastroenterology and Hepatology, Baylor University Medical Center, Dallas, Texas.
10
Division of Hepatology, Mayo Clinic Arizona, Phoenix, Arizona.
11
Division of Gastroenterology and Hepatology, University of California, San Diego, California.
12
Division of Gastroenterology and Hepatology, University of Miami, Miami, Florida.
13
Division of Infectious Diseases, Johns Hopkins University, Lutherville, Maryland.
14
Division of Gastroenterology and Hepatology, University of Kansas Medical Center Research Institute, Kansas City, Kansas.
15
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
16
Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan.
17
Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana.
18
Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
19
Division of Gastroenterology, Washington University, Saint Louis, Missouri.
20
Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina.
21
Division of Transplant Surgery, New York University School of Medicine, New York, New York.
22
Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
23
Gilead Sciences, Inc, Foster City, California.
24
Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
25
Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 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 assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point 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 (nontransplant), 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. ClinTrials.gov: NCT01938430.

KEYWORDS:

Decompensated Cirrhosis; Fibrosing Cholestatic Hepatitis; Hepatitis C Virus Infection; Liver Transplantation

Comment in

PMID:
25985734
DOI:
10.1053/j.gastro.2015.05.010
[Indexed for MEDLINE]
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