Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Clinical and Laboratory Assessments
2.3. DNA Extraction and IL28B Genotyping
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Treatment Response and Efficacy of Combination Treatment with Ledipasvir plus Sofosbuvir
3.3. Analysis of Resistance-Associated Variants (RAVs) in Relapsers to Ledipasvir plus Sofosbuvir
3.4. Safety in Ledipasvir plus Sofosbuvir Treatment
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Characteristics | All (n = 240) | Treatment-Naïve (n = 138) | Treatment-Experienced (n = 102) | p-Values 1 |
---|---|---|---|---|
Age (years) | 65.8 ± 11.6 | 67.5 ± 11.3 | 63.5 ± 11.6 | 0.00787 |
Gender (male/female) | 110/130 | 59/79 | 51/51 | 0.328 |
Interferon (naive/experienced) | 138/102 | 138/0 | 0/102 | N.A. |
HCV GT (1a/1b/1) | 6/206/28 | 4/120/14 | 2/86/14 | 0.994 |
HCV RNA (L/H) | 22/218 | 20/118 | 2/100 | 0.00194 |
Body weight (kg) | 56.9 ± 10.2 | 55.9 ± 11.1 | 58.2 ± 8.8 | 0.0851 |
Body length (cm) | 160 ± 9.5 | 160 ± 9.3 | 161 ± 9.7 | 0.420 |
History of HCC +/− | 43/197 | 26/112 | 17/85 | 0.792 |
Chronic hepatitis/cirrhosis | 153/87 | 88/50 | 65/37 | 0.897 |
Liver stiffness (kPa) | 11.4 ± 12.7 | 10.8 ± 12.4 | 12.2 ± 13.1 | 0.399 |
AST (IU/L) | 51.4 ± 32.0 | 48.1 ± 24.2 | 55.9 ± 39.9 | 0.0617 |
ALT (IU/L) | 46.9 ± 40.2 | 41.6 ± 26.9 | 54.0 ± 52.5 | 0.0179 |
Hemoglobin (g/dL) | 13.4 ± 1.6 | 13.4 ± 1.5 | 13.5 ± 1.6 | 0.620 |
Platelets (×104/μL) | 15.3 ± 6.8 | 15.7 ± 7.5 | 14.9 ± 5.7 | 0.368 |
eGFR (mL/min/1.73 m2) | 74.4 ± 17.9 | 73.2 ± 16.7 | 76.3 ± 19.6 | 0.188 |
Characteristics | All (n = 240) | Treatment-Naïve (n = 138) | Treatment-Experienced (n = 102) | p-Values 1 |
---|---|---|---|---|
HCV undetectable no. (%) | ||||
During treatment | ||||
At 4 w | 177 (73.8) | 106 (76.8) | 71 (69.6) | 0.221 |
At 8 w | 237 (98.8) | 136 (98.6) | 101 (99.0) | 0.791 |
At 12 w | 239 (99.6) | 137 (99.3) | 102 (100) | 0.879 |
After treatment | ||||
Post 4 w | 238 (99.2) | 137 (99.3) | 101 (99.0) | 0.615 |
Post 8 w | 236 (98.3) | 136 (98.6) | 100 (98.0) | 0.838 |
Post 12 w | 236 (98.3) | 136 (98.6) | 100 (98.0) | 0.838 |
Virological failure | ||||
Discontinuation | 1 | 1/138 (0.7) | 0/102 (0) | 0.879 |
Relapse | 2 | 0/138 (0) | 2/102 (2.0) | 0.350 |
Lost due to AEs | 1 | 1/138 (0.7) | 0/102 (0) | 0.879 |
No. | Age/Gender | Previous Treatment Response | GT | Cirrhosis/HCC | Efficacies | Adherence >80% | NS5A-L31 | NS5A-Y93 | NS5B-S282 |
---|---|---|---|---|---|---|---|---|---|
1 | 66/Male | PegIFN/RBV null response | 1b | Yes/+ | Relapse (post 4 w) | Yes | M | M | W |
2 | 58/Male | IFN null response | 1b | Yes/− | Relapse (post 8 w) | Yes | M | W | W |
© 2017 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Kanda, T.; Yasui, S.; Nakamura, M.; Suzuki, E.; Arai, M.; Ooka, Y.; Ogasawara, S.; Chiba, T.; Saito, T.; Haga, Y.; et al. Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors. Int. J. Mol. Sci. 2017, 18, 906. https://doi.org/10.3390/ijms18050906
Kanda T, Yasui S, Nakamura M, Suzuki E, Arai M, Ooka Y, Ogasawara S, Chiba T, Saito T, Haga Y, et al. Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors. International Journal of Molecular Sciences. 2017; 18(5):906. https://doi.org/10.3390/ijms18050906
Chicago/Turabian StyleKanda, Tatsuo, Shin Yasui, Masato Nakamura, Eiichiro Suzuki, Makoto Arai, Yoshihiko Ooka, Sadahisa Ogasawara, Tetsuhiro Chiba, Tomoko Saito, Yuki Haga, and et al. 2017. "Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors" International Journal of Molecular Sciences 18, no. 5: 906. https://doi.org/10.3390/ijms18050906