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

Izumi, Namiki; Takehara, Tetsuo; Chayama, Kazuaki; Yatsuhashi, Hiroshi; Takaguchi, Koichi; Ide, Tatsuya; Kurosaki, Masayuki; Ueno, Yoshiyuki; Toyoda, Hidenori; Kakizaki, Satoru; Tanaka, Yasuhito; Kawakami, Yoshiiku; Enomoto, Hirayuki; Ikeda, Fusao; Jiang, Deyuan; De-Oertel, Shampa; McNabb, Brian; Stamm, Luisa M.; Brainard, Diana M.; McHutchison, John G.; Mochida, Satoshi; Mizokami, Masashi

doi:10.1007/s12072-018-9878-6

Cited by 42 publications

(39 citation statements)

References 19 publications

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“…27 Patients who fail DAA therapy often achieve a favorable outcome when subsequently treated with GLE/PIB or velpatasvir/SOF plus ribavarin. 28,29 However, when poor renal function or anemia prevents the use of velpatasvir/SOF plus ribavirin, and GLE/PIB cannot be continued because of rash or another adverse drug reaction, EBR/GZR could be an option, provided the patient lacks an NS5A-L31/-Y93 double mutation, although further investigation is required. Two of the treatment failure cases were patients with NS5A double mutation, but without a history of DAA therapy.…”

Section: Discussionmentioning

confidence: 99%

Real‐world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group

Mashiba

Joko

Kurosaki

et al. 2019

Hepatology Research

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Aim The present study aimed to determine the real‐world efficacy and safety of the non‐structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. Methods This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post‐treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. Results Treatment outcomes for EBR/GZR were good in direct‐acting antiviral (DAA)‐naïve patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A‐L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A‐L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A‐Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91–16 940; P < 0.0001) was identified as an independent predictor of treatment failure. No serious adverse events were observed with EBR/GZR therapy. Conclusions The SVR rate of EBR/GZR would have been 100% in patients without either a history of DAA therapy or double mutation. This combination of drugs could be safely given and is, thus, considered a highly useful first‐line treatment for DAA‐naïve patients with HCV.

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Section: Discussionmentioning

confidence: 99%

Real‐world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group

Mashiba

Joko

Kurosaki

et al. 2019

Hepatology Research

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“…For patients with previous DAA treatment failures, 12-week SOF/VEL/voxilaprevir (VOX) and 24-week SOF/VEL plus ribavirin treatment for patients with HCV-1-6 infection have been approved. [22][23][24] For HCV-1 infected patients, 12-week GLE/PIB treat-ment for prior NS3/4A protease inhibitor-experienced patients and 16-week GLE/PIB treatment for prior NS5A inhibitor-experienced patients have also been approved. 25 Recently, 179 DAA-experienced patients were treated with SOF/VEL/VOX with or without RBV in the real-world setting.…”

Section: Multiple Daa Treatment Failuresmentioning

confidence: 99%

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy

Huang

2020

Clin Mol Hepatol

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The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.

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“…In Japan, SOF/VEL with a ribavirin regimen has been approved for patients with DAA failure . Two of three patients with P32 deletion achieved an SVR with SOF/VEL with a ribavirin regimen.…”

Section: Discussionmentioning

confidence: 99%

Viral and host factors are associated with retreatment failure in hepatitis C patients receiving all‐oral direct antiviral therapy

Mawatari

Oda

Kumagai

et al. 2020

Hepatology Research

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Aim: Direct-acting antiviral (DAA) therapy for hepatitis C virus is associated with high sustained virologic response rates. However, patients for whom DAA therapy fails acquire resistanceassociated substitutions (RASs). We therefore evaluated the efficacy of DAA retreatment and factors associated with retreatment failure.Methods: Non-structural 5A RASs were investigated at the start of DAA therapy and at treatment failure in 64 patients with hepatitis C virus genotype 1b for whom DAA combination therapy had failed. A total of 59 patients were introduced to DAA retreatment. The factors associated with retreatment failure were investigated.Results: A total of 20 of 43 (46.5%) daclatasvir + asunaprevirtreated patients with virologic failure had no RASs at baseline, and three (15%) acquired P32 deletion RASs. Four of seven sofosbuvir/ledipasvir-treated patients with virologic failure had more than two RASs of NS5A at baseline. The sustained virologic response rates on retreatment were as follows: sofosbuvir/ledipasvir, 81.8%; with elbasvir + grazoprevir, 0%; and glecaprevir/pibrentasvir, 87.5%. Patients for whom sofosbuvir/ledipasvir or elbasvir + grazoprevir failed achieved sustained virologic response with glecaprevir/pibrentasvir. Two of three patients for whom glecaprevir/pibrentasvir retreatment failed had Q24/L28/R30 and A92K RASs; the other had P32 deletion RAS at baseline. Interestingly, 10 of 11 patients with retreatment failure had the interleukin (IL)-28B singlenucleotide polymorphism (SNP) minor allele. A multivariate analysis showed that the IL28B SNP minor allele (P = 0.005, odds ratio 28.291) was an independent risk factor for retreatment failure.Conclusions: In addition to viral factors (e.g. Q24, L28, R30, and A92 or P32 deletion RASs), host factors (e.g. IL28B SNP) are associated with DAA retreatment failure.

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

Cited by 42 publications

References 19 publications

Real‐world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group

Real‐world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy

Viral and host factors are associated with retreatment failure in hepatitis C patients receiving all‐oral direct antiviral therapy

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