TY - JOUR
T1 - Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients with Advanced Liver Disease
AU - Charlton, Michael
AU - Everson, Gregory T.
AU - Flamm, Steven L.
AU - Kumar, Princy
AU - Landis, Charles
AU - Brown, Robert S.
AU - Fried, Michael W.
AU - Terrault, Norah A.
AU - O'Leary, Jacqueline G.
AU - Vargas, Hugo E.
AU - Kuo, Alexander
AU - Schiff, Eugene
AU - Sulkowski, Mark S.
AU - Gilroy, Richard
AU - Watt, Kymberly D.
AU - Brown, Kimberly
AU - Kwo, Paul
AU - Pungpapong, Surakit
AU - Korenblat, Kevin M.
AU - Muir, Andrew J.
AU - Teperman, Lewis
AU - Fontana, Robert J.
AU - Denning, Jill
AU - Arterburn, Sarah
AU - Dvory-Sobol, Hadas
AU - Brandt-Sarif, Theo
AU - Pang, Phillip S.
AU - McHutchison, John G.
AU - Reddy, K. Rajender
AU - Afdhal, Nezam
N1 - Publisher Copyright:
© 2015 AGA Institute.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Decompensated Cirrhosis
KW - Fibrosing Cholestatic Hepatitis
KW - Hepatitis C Virus Infection
KW - Liver Transplantation
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U2 - 10.1053/j.gastro.2015.05.010
DO - 10.1053/j.gastro.2015.05.010
M3 - Article
C2 - 25985734
AN - SCOPUS:84938953785
SN - 0016-5085
VL - 149
SP - 649
EP - 659
JO - Gastroenterology
JF - Gastroenterology
IS - 3
ER -