Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events

Tatsuo Kanda; Shin Yasui; Masato Nakamura; Shingo Nakamoto; Koji Takahashi; Shuang Wu; Reina Sasaki; Yuki Haga; Sadahisa Ogasawara; Tomoko Saito; Kazufumi Kobayashi; Soichiro Kiyono; Yoshihiko Ooka; Eiichiro Suzuki; Tetsuhiro Chiba; Hitoshi Maruyama; Mitsuhiko Moriyama; Naoya Kato

doi:10.18632/oncotarget.24620

Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events

Oncotarget. 2018 Mar 23;9(22):16263-16270. doi: 10.18632/oncotarget.24620.

Authors

Tatsuo Kanda^{1

2}, Shin Yasui², Masato Nakamura², Shingo Nakamoto^{2

3}, Koji Takahashi², Shuang Wu², Reina Sasaki², Yuki Haga², Sadahisa Ogasawara², Tomoko Saito², Kazufumi Kobayashi², Soichiro Kiyono², Yoshihiko Ooka², Eiichiro Suzuki², Tetsuhiro Chiba², Hitoshi Maruyama², Mitsuhiko Moriyama¹, Naoya Kato²

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.
² Department of Gastroenterology, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
³ Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.

Abstract

Background: Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen.

Case summary: Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks.

Conclusion: Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.

Keywords: direct-acting antiviral failure; hepatitis C virus; ledipasvir; ombitasvir; resistance-associated substitutions.