Successful retreatment with sofosbuvir plus ledipasvir for cirrhotic patients with hepatitis C virus genotype 1b, who discontinued the prior treatment with asunaprevir plus daclatasvir: A case series and review of the literature
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Yuki Haga1, Tatsuo Kanda1,2, Shin Yasui1, Masato Nakamura1, Yoshihiko Ooka1, Koji Takahashi1, Shuang Wu1, Shingo Nakamoto1,3, Makoto Arai1, Tetsuhiro Chiba1, Hitoshi Maruyama1, Osamu Yokosuka1, Nobuo Takada4, Mitsuhiko Moriyama2, Fumio Imazeki1,5 and Naoya Kato1
1 Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan
2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
3 Department of Molecular Virology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan
4 Department of Internal Medicine, Toho University Sakura Medical Center, Shimoshizu, Sakura, Japan
5 Safety and Health Organization, Chiba University, Yayoicho, Inage-ku, Chiba, Japan
Tatsuo Kanda, email:
Keywords: hepatitis C virus; direct-acting antiviral failure; non-structural 5A (NS5A) inhibitors; resistance-associated variants; case reports
Received: June 20, 2017 Accepted: December 23, 2017 Published: December 29, 2017
Background: Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only ~70% SVR rates.
Case summary: Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment.
Conclusion: Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment.
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