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

Abstract

BackgroundInterferon-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 summaryThree 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.ConclusionRetreatment 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.

Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals

“…Prior studies have suggested that there is an association between the duration of prior DAA treatment and success in retreatment, with patients treated with shorter durations of all-oral NS5A inhibitor-based DAA therapy (4–8 weeks) having higher retreatment SVR rates compared to those initially treated for longer durations (10–12 weeks) [ 19 , 20 ], a phenomenon, perhaps, resulting from greater virologic resistance developing during longer treatment. In the current study, the median duration of most recent prior DAA treatment was 12–14 weeks, and 95% of patients had baseline NS5A RASs.…”

Sofosbuvir/Velpatasvir - A Promising Treatment for Chronic Hepatitis C Virus Infection

“…Patients treated for shorter durations (four-eight weeks) with all-oral non-structural protein 5A (NS5A) direct-acting antiviral (DAA) had higher re-treatment sustained virologic response (SVR) rates than those initially treated for longer durations (10-12 weeks) [29]. The brief therapy ends in treatment failure owing to the treatment-emergent hepatitis C virus (HCV) NS5A resistance-associated variants (RAVs) [30].…”

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

“…In our previous report [ 15 ], one patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10 and had a treatment-emergent HCV NS5A RAS-Y93H did not achieve SVR with the combination retreatment of sofosbuvir and ledipasvir for 12 weeks. The present study supported retreatment with the combination of grazoprevir and elbasvir, but it should be avoided by HCV GT1b-infected patients who discontinued the initial interferon-free treatment with HCV NS5A inhibitor-including regimens at more than 4 weeks after the commencement of the initial treatment [ 16 ].…”

“…Previously, we reported that 12-week combination regimen of ledipasvir and sofosbuvir is an effective option for HCV GT1b patients without treatment-emergent HCV NS5A RASs, who discontinue the combination of daclatasvir and asunaprevir within 4 weeks [ 16 ]. In the present study, we showed the 12-week combination regimens of grazoprevir and elbasvir is an effective retreatment option for HCV GT1b patients with or without HCV NS5A RASs, who discontinue the initial interferon-free treatment with HCV NS5A inhibitor-including regimens due to adverse events within 2 weeks.…”

“…We recently reported that retreatment with ledipasvir and sofosbuvir is effective for HCV GT1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks [ 16 ]. In the present case series, we reported that the 12-week retreatment with grazoprevir and elbasvir is effective for HCV GT1b patients who discontinued the NS5A inhibitor-including regimens within 2 weeks.…”