Details

Autor(en) / Beteiligte

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

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

Ist Teil von

• Hepatology international, 2020-03, Vol.14 (2), p.225-238

Ort / Verlag

New Delhi: Springer India

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.