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

Publication ,  Journal Article
Charlton, M; Everson, GT; Flamm, SL; Kumar, P; Landis, C; Brown, RS; Fried, MW; Terrault, NA; O'Leary, JG; Vargas, HE; Kuo, A; Schiff, E ...
Published in: Gastroenterology
September 2015

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.

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Published In

Gastroenterology

DOI

EISSN

1528-0012

Publication Date

September 2015

Volume

149

Issue

3

Start / End Page

649 / 659

Location

United States

Related Subject Headings

  • Uridine Monophosphate
  • United States
  • Treatment Outcome
  • Time Factors
  • Sofosbuvir
  • Ribavirin
  • Middle Aged
  • Male
  • Liver Transplantation
  • Liver Cirrhosis
 

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Charlton, M., Everson, G. T., Flamm, S. L., Kumar, P., Landis, C., Brown, R. S., … SOLAR-1 Investigators. (2015). Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology, 149(3), 649–659. https://doi.org/10.1053/j.gastro.2015.05.010
Charlton, Michael, Gregory T. Everson, Steven L. Flamm, Princy Kumar, Charles Landis, Robert S. Brown, Michael W. Fried, et al. “Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.Gastroenterology 149, no. 3 (September 2015): 649–59. https://doi.org/10.1053/j.gastro.2015.05.010.
Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS, et al. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology. 2015 Sep;149(3):649–59.
Charlton, Michael, et al. “Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.Gastroenterology, vol. 149, no. 3, Sept. 2015, pp. 649–59. Pubmed, doi:10.1053/j.gastro.2015.05.010.
Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS, Fried MW, Terrault NA, O’Leary JG, Vargas HE, Kuo A, Schiff E, Sulkowski MS, Gilroy R, Watt KD, Brown K, Kwo P, Pungpapong S, Korenblat KM, Muir AJ, Teperman L, Fontana RJ, Denning J, Arterburn S, Dvory-Sobol H, Brandt-Sarif T, Pang PS, McHutchison JG, Reddy KR, Afdhal N, SOLAR-1 Investigators. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology. 2015 Sep;149(3):649–659.
Journal cover image

Published In

Gastroenterology

DOI

EISSN

1528-0012

Publication Date

September 2015

Volume

149

Issue

3

Start / End Page

649 / 659

Location

United States

Related Subject Headings

  • Uridine Monophosphate
  • United States
  • Treatment Outcome
  • Time Factors
  • Sofosbuvir
  • Ribavirin
  • Middle Aged
  • Male
  • Liver Transplantation
  • Liver Cirrhosis