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Hepatology International
Erschienen in:

03.03.2020 | Original Article

The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study

verfasst von: Akito Nozaki, Masanori Atsukawa, Chisa Kondo, Hidenori Toyoda, Makoto Chuma, Makoto Nakamuta, Haruki Uojima, Koichi Takaguchi, Hiroki Ikeda, Tsunamasa Watanabe, Shintaro Ogawa, Norio Itokawa, Taeang Arai, Atsushi Hiraoka, Toru Asano, Shinichi Fujioka, Tadashi Ikegami, Toshihide Shima, Chikara Ogawa, Takehiro Akahane, Noritomo Shimada, Shinya Fukunishi, Hiroshi Abe, Akihito Tsubota, Takuya Genda, Hironao Okubo, Shigeru Mikami, Asahiro Morishita, Akio Moriya, Joji Tani, Yoshihiko Tachi, Naoki Hotta, Toru Ishikawa, Takeshi Okanoue, Yasuhito Tanaka, Takashi Kumada, Katsuhiko Iwakiri, Shin Maeda, the KTK49 Liver Study Group

Erschienen in: Hepatology International | Ausgabe 2/2020

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Abstract

Background

Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment.

Methods

In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed.

Results

Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10–5; genotype 2 vs. 3, p = 3.28 × 10–5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1–3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4–5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512–148.550), p value (p = 4.06 × 10–5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153–13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4–5 (41.6% [79/190]) than CKD stage 1–3 (26.1% [319/1220]) patients (p = 2.00 × 10–5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10–18) patients.

Conclusions

G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.
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Metadaten
Titel
The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study
verfasst von
Akito Nozaki
Masanori Atsukawa
Chisa Kondo
Hidenori Toyoda
Makoto Chuma
Makoto Nakamuta
Haruki Uojima
Koichi Takaguchi
Hiroki Ikeda
Tsunamasa Watanabe
Shintaro Ogawa
Norio Itokawa
Taeang Arai
Atsushi Hiraoka
Toru Asano
Shinichi Fujioka
Tadashi Ikegami
Toshihide Shima
Chikara Ogawa
Takehiro Akahane
Noritomo Shimada
Shinya Fukunishi
Hiroshi Abe
Akihito Tsubota
Takuya Genda
Hironao Okubo
Shigeru Mikami
Asahiro Morishita
Akio Moriya
Joji Tani
Yoshihiko Tachi
Naoki Hotta
Toru Ishikawa
Takeshi Okanoue
Yasuhito Tanaka
Takashi Kumada
Katsuhiko Iwakiri
Shin Maeda
the KTK49 Liver Study Group
Publikationsdatum
03.03.2020
Verlag
Springer India
Erschienen in
Hepatology International / Ausgabe 2/2020
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-020-10019-z

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