Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.
Gastroenterology. 2015 Sep;149(3):649-59.
Charlton M1, Everson GT2, Flamm SL3, Kumar P4, Landis C5, Brown RS Jr6, Fried MW7, Terrault NA8, O’Leary JG9, Vargas HE10, Kuo A11, Schiff E12, Sulkowski MS13, Gilroy R14, Watt KD15, Brown K16, Kwo P17, Pungpapong S18, Korenblat KM19, Muir AJ20, Teperman L21, Fontana RJ22, Denning J23, Arterburn S23, Dvory-Sobol H23, Brandt-Sarif T23, Pang PS23, McHutchison JG23, Reddy KR24, Afdhal N25; SOLAR-1 Investigators.
Kumar P, Schiff E, Afdhal N, Brown RS, Fried M, Kowdley K, Terrault N, Charlton M, Kwo P, Flamm S, Lake J, Everson G, Sulkowski M, Curry M, Reddy R, Teperman L, Vargas H, Pungpapong S, Muir A, Zaman A, Brown K, Landis C, Kuo A, Fontana R, O’Leary J, Gilroy R, Shaikh O, Korenblat K, Stravitz R, Watt K, Menon N, Bredfeldt J, Romero-Marrero C.
1Division of Hepatology and Liver Transplantation, Intermountain Medical Center, Salt Lake City, Utah. Electronic address: firstname.lastname@example.org.
2Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado.
3Division of Gastroenterology and Hepatology, Northwestern Feinberg School of Medicine, Chicago, Illinois.
4Division of Infectious Diseases, Georgetown University, Washington, District of Columbia.
5Division of Gastroenterology and Hepatology, University of Washington/Harborview Medical Center, Seattle, Washington.
6Division of Digestive and Liver Diseases, Columbia University Medical Center/New York Presbyterian, New York, New York.
7Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill/University of North Carolina School of Medicine, Chapel Hill, North Carolina.
8Division of Gastroenterology and Hepatology, University of California, San Francisco, California.
9Division of Gastroenterology and Hepatology, Baylor University Medical Center, Dallas, Texas.
10Division of Hepatology, Mayo Clinic Arizona, Phoenix, Arizona.
11Division of Gastroenterology and Hepatology, University of California, San Diego, California.
12Division of Gastroenterology and Hepatology, University of Miami, Miami, Florida.
13Division of Infectious Diseases, Johns Hopkins University, Lutherville, Maryland.
14Division of Gastroenterology and Hepatology, University of Kansas Medical Center Research Institute, Kansas City, Kansas.
15Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
16Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan.
17Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana.
18Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
19Division of Gastroenterology, Washington University, Saint Louis, Missouri.
20Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina.
21Division of Transplant Surgery, New York University School of Medicine, New York, New York.
22Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
23Gilead Sciences, Inc, Foster City, California.
24Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
25Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: email@example.com.
BACKGROUND & AIMS:
There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease.
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).
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.
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.