Eiichi Ogawa1, Norihiro Furusyo1, Hideyuki Nomura2, Kazufumi Dohmen3, Nobuhiko Higashi4, Kazuhiro Takahashi5, Akira Kawano6, Koichi Azuma7, Takeaki Satoh8, Makoto Nakamuta9, Toshimasa Koyanagi10, Masaki Kato11, Shinji Shimoda12, Eiji Kajiwara13, Jun Hayashi14. 1. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 2. The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan. 3. Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan. 4. Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan. 5. Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan. 6. Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan. 7. Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan. 8. Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan. 9. Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan. 10. Department of Medicine, Fukuoka City Hospital, Fukuoka, Japan. 11. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 12. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 13. Kajiwara Clinic, Kitakyushu, Japan. 14. Kyushu General Internal Medicine Center, Haradoi Hospital, Higashi-Ku, Fukuoka, 812-8582, Japan. hayashij1949@haradoi-hospital.com.
Abstract
BACKGROUND: Little real-world cohort data has been reported for Asians who have received interferon-free regimens with sofosbuvir (SOF) for chronic hepatitis C virus (HCV) infection. We evaluated the effectiveness and safety in clinical practice of ledipasvir (LDV) plus SOF for Japanese patients infected with HCV genotype 1. METHODS: This large, multicenter, real-world cohort study consisted of 772 patients treatment-naive or -experienced, with or without compensated cirrhosis, who were treated with LDV (90 mg)/SOF (400 mg) for a fixed 12-week duration. Direct sequence analysis of the NS5A genes (L31 and Y93) was performed at baseline. RESULTS: Almost all (99.6%) were infected with HCV genotype 1b. The overall sustained virological response 12 weeks after the end of treatment (SVR12) rate was 98.8% (763/772). Multivariable logistic regression analysis extracted male (odds ratio [OR] 6.62, p = 0.024), cirrhosis (OR 20.1, p = 0.0054), and baseline NS5A resistance-associated variants (RAVs) (OR 29.3, p = 0.0018) as independently associated with treatment failure. Notably, the SVR12 rate for cirrhosis patients with baseline NS5A RAVs (87.5%, 49/56) was statistically lower than for the other groups. This tendency was found except for patients with prior daclatasvir/asunaprevir failure. All patients with treatment failure had NS5A Y93H at relapse, whether or not they had NS5A RAVs at baseline. Serious adverse effects were very rare, and discontinuation was required for only five (0.6%) patients. CONCLUSIONS: LDV/SOF for HCV genotype 1b was exceptionally effective, however, NS5A RAVs undermined the virological effect for cirrhosis patients. Moreover, LDV/SOF was shown to be safe, irrespective of age or fibrosis status.
BACKGROUND: Little real-world cohort data has been reported for Asians who have received interferon-free regimens with sofosbuvir (SOF) for chronic hepatitis C virus (HCV) infection. We evaluated the effectiveness and safety in clinical practice of ledipasvir (LDV) plus SOF for Japanese patients infected with HCV genotype 1. METHODS: This large, multicenter, real-world cohort study consisted of 772 patients treatment-naive or -experienced, with or without compensated cirrhosis, who were treated with LDV (90 mg)/SOF (400 mg) for a fixed 12-week duration. Direct sequence analysis of the NS5A genes (L31 and Y93) was performed at baseline. RESULTS: Almost all (99.6%) were infected with HCV genotype 1b. The overall sustained virological response 12 weeks after the end of treatment (SVR12) rate was 98.8% (763/772). Multivariable logistic regression analysis extracted male (odds ratio [OR] 6.62, p = 0.024), cirrhosis (OR 20.1, p = 0.0054), and baseline NS5A resistance-associated variants (RAVs) (OR 29.3, p = 0.0018) as independently associated with treatment failure. Notably, the SVR12 rate for cirrhosis patients with baseline NS5A RAVs (87.5%, 49/56) was statistically lower than for the other groups. This tendency was found except for patients with prior daclatasvir/asunaprevir failure. All patients with treatment failure had NS5A Y93H at relapse, whether or not they had NS5A RAVs at baseline. Serious adverse effects were very rare, and discontinuation was required for only five (0.6%) patients. CONCLUSIONS: LDV/SOF for HCV genotype 1b was exceptionally effective, however, NS5A RAVs undermined the virological effect for cirrhosis patients. Moreover, LDV/SOF was shown to be safe, irrespective of age or fibrosis status.
Entities:
Keywords:
Cirrhosis; DAA; Hepatitis C virus; Ledipasvir; Sofosbuvir
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