Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures

Osawa, Mitsutaka; Imamura, Michio; Teraoka, Yuji; Uchida, Takuro; Morio, Kei; Fujino, Hatsue; Nakahara, Takashi; Ono, Atsushi; Murakami, Eisuke; Kawaoka, Tomokazu; Miki, Daiki; Tsuge, Masataka; Hiramatsu, Akira; Aikata, Hiroshi; Hayes, C. Nelson; Chayama, Kazuaki

doi:10.1007/s00535-018-1520-9

Cited by 40 publications

(38 citation statements)

References 21 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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“…Our search retrieved 410 articles, of which 64 were included for full‐text review and eligibility assessment. Seventeen studies fulfilled the eligibility criteria and were included in the analysis . The reasons for excluding the remaining studies are detailed in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…The patient and study characteristics are detailed in Table . Three studies reported only the number of baseline polymorphisms and not the individual number of patients with the substitutions . The corresponding authors were contacted regarding the information.…”

Section: Resultsmentioning

confidence: 99%

“…All the studies used a 15% detection cut‐off for evaluation of RAS. Osawa et al used deep sequencing, Akuta et al used direct‐sequencing and Gane et al used population sequencing methods while all the remaining studies used next‐generation sequencing techniques. Baseline NS5a and NS3 RAS were assessed in all the studies, NS5b RAS was evaluated only in one study by Akuta et al…”

Section: Resultsmentioning

confidence: 99%

“…As the presence of RAS was considered at the time of inclusion of patients, the studies were considered to be at low risk of bias. The real‐world studies were considered to have a moderate risk of bias due to highly selective patient populations . The assessed risk of bias is detailed in Table S1.…”

Section: Resultsmentioning

confidence: 99%

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Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

Singh

Maitra

Singh

et al. 2020

Aliment Pharmacol Ther

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Background:The effect of baseline resistance-associated substitutions (RAS) on the sustained virologic response at 12 weeks (SVR12) among chronic hepatitis C (CHC) patients receiving the second generation, pan-genotypic glecaprevir/pibrentasvir (G/P) regimen is unclear. Aim:To assess the effect of RAS on the SVR12 in CHC patients treated with G/P regimen. Methods: The EMBASE, MEDLINE and Cochrane central register of controlled trials databases were searched for relevant studies published before 1 March 2019.The principal outcome was to compare the SVR12 in CHC patients with and without baseline RAS, particularly in genotype-1, genotype-3 and direct-acting anti-virals (DAAs) failure patients. The outcomes were pooled using a random-effects model and odds ratio (OR) was calculated. The risk of bias was assessed using the Cochrane risk of bias tools for randomised and nonrandomised interventional studies. Results: After initially identifying 410 studies, 3302 patients from 17 studies were included. Among 50 cases of virologic failures, 48% had genotype-3 infection, 44% genotype-1 infection and 36% DAA-failure patients. Baseline RAS were present in 44(88%) patients. The most common NS5a and NS3 mutations were Y93H and A166S respectively. The odds of SVR12 were significantly reduced in patients with any baseline RAS (NS3 and/or NS5a) (OR 0.32, 95%C I[0.15, 0.65], I 2 = 0%) and NS5a substitutions (OR 0.36, 95%CI [0.18,0.73]). The impact of RAS on SVR12 was significant among genotype-3 patients, but not among genotype-1 or DAA-failure cases. The presence of Y93H and A30K mutations significantly impacted SVR12 rates in genotype-3 patients. Conclusion: Baseline NS3 or NS5a RAS, especially the NS5a substitutions-A30K, Y93H, decrease the odds of achieving SVR12 in genotype-3 CHC patients. | 491 SINGH et al.

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NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir

et al. 2019

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Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures

Cited by 40 publications

References 21 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

Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir

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