Ledipasvir‐sofosbuvir for treating Japanese patients with chronic hepatitis C virus genotype 2 infection

Section: Discussionmentioning

confidence: 99%

Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group

Akahane¹,

Kurosaki

Itakura

et al. 2018

“…First, we introduced RAVs, which were mainly observed in patients who failed to respond to combination therapy with NS3, NS5A, and/or NS5B inhibitors (NS3 D168E, NS5A Y93H, P32 deletion, F28S, F28S/M31I, and NS5B S282 T) in a JFH‐1‐based genotype 2b/2a chimeric virus, which was previously established in our laboratory and showed high replication ability (Fig. ).…”

Section: Resultsmentioning

confidence: 99%

“…Until recently, because most clinical trials exclude patients who failed to respond to DAAs, retreatment outcomes for patients who had such RAVs have not been elucidated. In patients who failed to respond to DAA‐containing regimens, RAVs in D168E, NS5A F28S, P32 deletion, or NS5B S282 T, which are rarely detected as naturally occurring RAVs, were observed . These RAVs are thought to be cross‐resistant to the same class of DAAs; however, the degree of resistance and the sensitivity to other anti‐HCV reagents have not been clarified.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a phase III clinical trial of glecaprevir and pibrentasvir for patients who previously failed to respond to DAAs in Japan showed that the RAV NS3 D168E was the most prevalent RAV in the HCV NS3 region . Moreover, in a phase III trial for sofosbuvir/ledipasvir in patients with genotype 2 HCV infection, the well‐known but rare emerging RAV NS5B S282 T was reported …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of resistance‐associated variants in genotype 2 hepatitis C virus on viral replication and susceptibility to antihepatitis C virus drugs

Suda

Kimura

Shigesawa

et al. 2019

Aims Development of direct‐acting antivirals (DAAs) has made antihepatitis C virus (HCV) treatment highly safe and effective. However, the emergence of resistant‐associated variants (RAVs) after failure of DAA therapy affects retreatment outcomes. In particular, genotype 1 HCV with P32 deletion has been reported to be highly resistant to all approved non‐structural protein (NS)5A inhibitors. However, analysis of RAVs in genotype 2 HCV has been limited. Accordingly, in this study, we evaluated the roles of genotype 2 HCV variants in antiviral drug efficacy. Methods We utilized HCV‐2b/2a (JFH‐1) chimeric virus (genotype 2a), which replicates more robustly than JFH‐1. We constructed various genotype 2a JFH‐1‐based HCV cell culture systems with NS3 (D168E), NS5A (F28S, F28S/M31I, P32 deletion, and Y93H), and NS5B (S282 T) RAVs and analyzed the replication ability and sensitivity to various anti‐HCV reagents. Results Genotype 2a‐based HCV with NS5A–P32 deletion could not replicate even in long‐term cultures. Genotype 2a‐based HCV with NS5A‐F28S/M31I showed significantly higher replication ability than the wild‐type strain, and replication could not be suppressed, even with high concentrations of NS5A inhibitors, including pibrentasvir and velpatasvir (<1000–10 000 fold‐resistance compared with the wild‐type strain). However, genotype 2a‐based HCV with NA5A‐F28S/M31I was sensitive to HCV protease inhibitor, NS5B inhibitor, interferon‐α, and ribavirin. Genotype 2a‐based HCV with NS5B‐S282 T was resistant to sofosbuvir, but was highly sensitive to ribavirin compared with the control. Conclusions When undertaking retreatment for genotype 2a HCV‐infected patients who fail to respond to DAAs, the optimized retreatment should be chosen according to the sensitivity of the emerging RAVs to anti‐HCV drugs.

“…In the present study, both patients with treatment failure had NS5A L31 M, but not NS5B RASs at baseline. However, RAS analysis showed that almost all patients (94–97%) with subtype 2a and 39–89% of those with subtype 2b originally had NS5A L31 M at baseline . In addition, the SVR rate for patients with NS5A RASs was extremely high (97.6%, 165/169) in clinical trials .…”

Section: Discussionmentioning

confidence: 99%

Ledipasvir and sofosbuvir for 12 weeks for hepatitis C virus genotype 2 infection: A propensity score matched analysis

Ogawa

Nomura

Nakamuta

et al. 2019

Aim Hepatitis C virus genotype 2 is common in East Asia, sub‐Saharan Africa, and Latin America. However, many countries in these areas lag behind other areas of the world in government approval for new direct‐acting antivirals. The aim of this study was to evaluate the treatment outcome of ledipasvir/sofosbuvir (LDV/SOF) for patients with chronic hepatitis C virus genotype 2 infection. Methods This is a two‐part multicenter, real‐world cohort study. Study 1 consisted of 58 consecutive patients who were treated with LDV/SOF for 12 weeks. Study 2 used propensity score matching for LDV/SOF (n = 58) and glecaprevir/pibrentasvir (n = 207) treatment groups (1:1) with a set of clinically important variables. Sustained viral response 12 weeks after the end of treatment (SVR12) and adverse events were evaluated in both studies. Results In study 1, the overall SVR12 rates of the intention‐to‐treat and modified intention‐to‐treat populations were 94.8% (55/58) and 96.5% (55/57), respectively. High SVR12 rates were observed in almost all subgroups, including older age, compensated cirrhosis, and treatment experience. In study 2, propensity score matching of the entire study population yielded 52 matched pairs with similar baseline characteristics. There were no statistically significant differences between the LDV/SOF (96.1%) and glecaprevir/pibrentasvir (98.0%) groups in the overall SVR12 rates of the modified intention‐to‐treat populations, and their rates of treatment discontinuation and adverse events were similar. Conclusions Treatment with LDV/SOF for hepatitis C virus genotype 2 resulted in a high rate of SVR12 and excellent tolerability. The outcomes of LDV/SOF were very similar to those of glecaprevir/pibrentasvir.