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

被引：25

作者：

Nozaki, Akito ^{[1
]}

Atsukawa, Masanori ^{[2
]}

Kondo, Chisa ^{[2
]}

Toyoda, Hidenori ^{[3
]}

Chuma, Makoto ^{[1
]}

Nakamuta, Makoto ^{[4
]}

Uojima, Haruki ^{[5
]}

Takaguchi, Koichi ^{[6
]}

Ikeda, Hiroki ^{[7
]}

Watanabe, Tsunamasa ^{[7
]}

Ogawa, Shintaro ^{[8
,9
]}

Itokawa, Norio ^{[10
]}

Arai, Taeang ^{[11
]}

Hiraoka, Atsushi ^{[12
]}

Asano, Toru ^{[13
]}

Fujioka, Shinichi ^{[14
]}

Ikegami, Tadashi ^{[15
]}

Shima, Toshihide ^{[16
]}

Ogawa, Chikara ^{[17
]}

Akahane, Takehiro ^{[18
]}

Shimada, Noritomo ^{[19
]}

Fukunishi, Shinya ^{[20
]}

Abe, Hiroshi ^{[21
]}

Tsubota, Akihito ^{[22
]}

Genda, Takuya ^{[23
]}

Okubo, Hironao ^{[24
]}

Mikami, Shigeru ^{[25
]}

Morishita, Asahiro ^{[26
]}

Moriya, Akio ^{[27
]}

Tani, Joji ^{[28
]}

Tachi, Yoshihiko ^{[29
]}

Hotta, Naoki ^{[30
]}

Ishikawa, Toru ^{[31
]}

Okanoue, Takeshi ^{[16
]}

Tanaka, Yasuhito ^{[8
,9
]}

Kumada, Takashi ^{[3
]}

Iwakiri, Katsuhiko ^{[2
]}

Maeda, Shin ^{[1
,32
]}

机构：

[1] Yokohama City Univ, Med Ctr, Gastroenterol Ctr, Minami Ku, 4-57 Urafune Cho, Yokohama, Kanagawa 2320024, Japan

[2] Nippon Med Sch, Div Gastroenterol & Hepatol, Dept Internal Med, Tokyo, Japan

[3] Ogaki Municipal Hosp, Dept Gastroenterol, Ogaki, Japan

[4] Natl Hosp Org Kyushu Med Ctr, Fukuoka, Japan

[5] Kitasato Univ, Sch Med, Dept Gastroenterol, Internal Med, Sagamihara, Kanagawa, Japan

[6] Kagawa Prefectural Cent Hosp, Dept Hepatol, Takamatsu, Kagawa, Japan

[7] St Marianna Univ, Sch Med, Dept Internal Med, Kawasaki, Kanagawa, Japan

[8] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi, Japan

[9] Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi, Japan

[10] Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, Div Gastroenterol, Inzai, Japan

[11] Musashikosugi Hosp, Nippon Med Sch, Dept Internal Med, Div Gastroenterol, Kawasaki, Kanagawa, Japan

[12] Ehime Prefectural Cent Hosp, Gastroenterol Ctr, Matsuyama, Ehime, Japan

[13] Tokyo Metropolitan Bokutoh Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo, Japan

[14] Okayama Saiseikai Gen Hosp, Dept Gastroenterol, Okayama, Japan

[15] Tokyo Med Univ, Ibaraki Med Ctr, Ibaraki, Japan

[16] Saiseikai Suita Hosp, Dept Gastroenterol & Hepatol, Suita, Osaka, Japan

[17] Takamatsu Red Cross Hosp, Dept Gastroenterol & Hepatol, Takamatsu, Kagawa, Japan

[18] Japanese Red Cross Ishinomaki Hosp, Dept Gastroenterol, Ishinomaki, Japan

[19] Otakanomori Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Kashiwa, Chiba, Japan

[20] Osaka Med Coll, Dept Internal Med 2, Osaka, Japan

[21] Shinmatsudo Cent Gen Hosp, Div Gastroenterol & Hepatol, Dept Internal Med, Matsudo, Chiba, Japan

[22] Jikei Univ, Sch Med, Core Res Facil Basic Sci, Tokyo, Japan

[23] Juntendo Shizuoka Univ Hosp, Dept Gastroenterol, Shizuoka, Japan

[24] Juntendo Nerima Univ Hosp, Dept Gastroenterol, Tokyo, Japan

[25] Kikkoman Gen Hosp, Dept Internal Med, Div Gastroenterol, Noda, Chiba, Japan

[26] Kagawa Univ, Dept Gastroenterol, Grad Sch Med, Takamatsu, Kagawa, Japan

[27] Mitoyo Gen Hosp, Dept Gastroenterol, Kannonji, Japan

[28] Yashima Gen Hosp, Dept Internal Med, Takamatsu, Kagawa, Japan

[29] Fujita Hlth Univ, Bantane Hosp, Sch Med, Nagoya, Aichi, Japan

[30] Masuko Mem Hosp, Dept Internal Med, Div Hepatol, Nagoya, Aichi, Japan

[31] Saiseikai Niigata Daini Hosp, Dept Hepatol, Niigata, Japan

[32] Yokohama City Univ, Grad Sch Med, Dept Gastroenterol, Yokohama, Kanagawa, Japan

来源：

HEPATOLOGY INTERNATIONAL | 2020年 / 14卷 / 02期

基金：

日本学术振兴会;

关键词：

Glecaprevir; Pibrentasvir; Chronic hepatitis C; Refractory factors; Multicenter study; GENOTYPE; 2; INFECTED PATIENTS; JAPANESE PATIENTS; HCV; PIBRENTASVIR; GLECAPREVIR; EFFICACY; SOFOSBUVIR; RATES;

D O I：

10.1007/s12072-020-10019-z

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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-naive patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 x 10(-5); genotype 2 vs. 3, p = 3.28 x 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 x 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 x 10(-5)). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 x 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.

引用

页码：225 / 238

页数：14

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