Caring Ambassadors Program Hepatitis C Literature Review © 2018 Caring Ambassadors Program Hepatitis C Newsletter www.HepCChallenge.org

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. Haga Y1, Kanda T1,2, Yasui S1, et al. Oncotarget. 2017 Dec 29;9(4):5509-5513. doi: 10.18632/oncotarget.23768. eCollection 2018 Jan 12. 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-1binfected 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. P. 1-5