Real-life effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous DAA failure

被引：78

作者：

Degasperi, Elisabetta ^{[1
,30
]}

Spinetti, Angiola ^{[2
,51
]}

Lombardi, Andrea ^{[3
]}

Landonio, Simona ^{[4
,38
]}

Rossi, Maria Cristina ^{[5
]}

Pasulo, Luisa ^{[6
,32
]}

Pozzoni, Pietro ^{[7
]}

Giorgini, Alessia ^{[8
,48
]}

Fabris, Paolo ^{[9
,87
]}

Romano, Antonietta ^{[10
,63
]}

Lomonaco, Lorenzo ^{[11
,91
]}

Puoti, Massimo ^{[12
,37
]}

Vinci, Maria ^{[13
,36
]}

Gatti, Federico ^{[14
,43
]}

Carolo, Giada ^{[15
,90
]}

Zoncada, Alessia ^{[16
,54
]}

Bonfanti, Paolo ^{[17
,58
]}

Russo, Francesco Paolo ^{[18
,63
]}

Aghemo, Alessio ^{[19
,46
]}

Soria, Alessandro ^{[20
,39
]}

Centenaro, Riccardo ^{[21
,61
]}

Maggiolo, Franco ^{[6
,33
]}

Rovere, Pierangelo ^{[22
,72
]}

Pasin, Francesca ^{[23
,63
]}

Paon, Veronica ^{[24
,89
]}

Faggiano, Giovanni ^{[25
,77
]}

Vario, Alessandro ^{[26
,69
]}

Grossi, Glenda ^{[27
]}

Soffredini, Roberta ^{[1
,30
]}

Carriero, Canio ^{[2
]}

Paolucci, Stefania ^{[28
]}

Noventa, Franco ^{[29
]}

Alberti, Alfredo ^{[23
,63
]}

Lampertico, Pietro ^{[1
,30
]}

Fagiuoli, Stefano ^{[6
,32
]}

D'Ambrosio, Roberta ^{[30
]}

Degasperi, Elisabetta ^{[1
,30
]}

Borghi, Marta ^{[30
]}

Perbellini, Riccardo ^{[30
]}

Gori, Andrea ^{[31
]}

Ferroni, Valentina ^{[31
]}

Pasulo, Luisa ^{[6
,32
]}

Manini, Maria Colpani Matteo ^{[32
]}

Cologni, Giuliana ^{[33
]}

Lazzaroni, Sergio ^{[34
]}

Del Poggio, Paolo ^{[35
]}

Vinci, Maria ^{[13
,36
]}

De Nicola, Stella ^{[36
]}

Mazzarelli, Chiara ^{[36
]}

Zucchetti, Teresa Angelini ^{[36
]}

机构：

[1] Univ Milan, Osped Maggiore Policlin, Fdn IRCCS Ca Granada, CRC AM & A Migliavacca Ctr Liver Dis Gastroentero, Milan, Italy

[2] ASST Spedali Civili Brescia, Infect Dis, Brescia, Italy

[3] Univ Pavia, Fdn IRCCS Policlin San Matteo, Infect Dis, Pavia, Italy

[4] Sacco Hosp, Infect Dis, Milan, Italy

[5] Treviso Hosp, Infect Dis, Treviso, Italy

[6] ASST Papa Giovanni XXIII, Bergamo HCV Network, Bergamo, Italy

[7] ASST Lecco Hosp LC, Internal Med, Lecce, Italy

[8] ASST Santi Paolo & Carlo, Gastroenterol & Hepatol, Milan, Italy

[9] Santorso Hosp, Infect Dis, Vicenza, Italy

[10] Univ Padua, Dept Med, Internal Med & Hepatol, Padua, Italy

[11] Bussolengo Hosp, Gastroenterol, Verona, Italy

[12] ASST Grande Osped Metropolitano Niguarda, Infect Dis, Milan, Italy

[13] ASST Grande Osped Metropolitano Niguarda, Gastroenterol & Hepatol, Milan, Italy

[14] ASST Ovest Milanese, Hosp Pharm, Legnano, MI, Italy

[15] Univ Verona, Infect Dis, Verona, Italy

[16] ASST Cremona, Infect Dis, Cremona, CR, Italy

[17] ASST Lecco Hosp LC, Infect Dis, Lecce, Italy

[18] Univ Hosp Padua, Gastroenterol & Multivisceral Transplant, Padua, Italy

[19] Humanitas Univ, IRCCS Humanitas Res Hosp, Internal Med & Hepatol, Pieve Emanuele, MI, Italy

[20] ASST Monza, San Gerardo Hosp, Infect Dis, Monza, MB, Italy

[21] ASST Melegnano Martesana, Internal Med, Vizzolo Predabissi, MI, Italy

[22] Legnago Hosp, Infect Dis, Verona, Italy

[23] Univ Padua, Dept Mol Med, Padua, Italy

[24] Univ Verona, Internal Med, Verona, Italy

[25] Rovigo Hosp, Infect Dis, Rovigo, Italy

[26] ULSS 17 Veneto Hosp, Hepatol, Este, PD, Italy

[27] Magenta Hosp MI, ASST Ovest Milanese, Internal Med, Magenta, Italy

[28] Policlin San Matteo, Fdn IRCCS, Microbiol & Virol Dept, Mol Virol Unit, Pavia, Italy

[29] QUOVADIS Profit Assoc, Padua, Italy

[30] Univ Milan, Gastroenterol & Hepatol, Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Milan, Italy

[31] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Infect Dis, Milan, Italy

[32] ASST Papa Giovanni XXIII, Gastroenterol, Bergamo, Italy

[33] ASST Papa Giovanni XXIII, Infect Dis, Bergamo, Italy

[34] MOA Locatelli Hosp, Piario, BG, Italy

[35] Policlin San Marco, Zingonia, BG, Italy

[36] ASST Grande Osped Metropolitano Niguarda, Gastroenterol & Hepatol, Milan, Italy

[37] ASST Grande Osped Metropolitano Niguarda, Infect Dis, Milan, Italy

[38] ASST Sacco, Infect Dis, Milan, Italy

[39] ASST Monza, San Gerardo Hosp, Infect Dis, Monza, Italy

[40] ASST Ovest Milanese, Infect Dis, Legnano, MI, Italy

[41] ASST Ovest Milanese, Internal Med, Legnano, MI, Italy

[42] ASST Ovest Milanese, Legnano, MI, Italy

[43] ASST Ovest Milanese, Hosp Pharm, Legnano, MI, Italy

[44] ASST Ovest Milanese, Internal Med, Abbiategrasso, MI, Italy

[45] Busto Arsizio Hosp, ASST Valle Olona, Infect Dis, Varese, Italy

[46] Humanitas Res Hosp, Internal Med, Pieve Emanuele, MI, Italy

[47] Univ Milan, San Giuseppe Hosp, Hepatol, Milan, Italy

[48] AAST Santi Paolo & Carlo, Internal Med, Milan, Italy

[49] AAST Santi Paolo & Carlo, Infect Dis, Milan, Italy

[50] AAST Santi Paolo & Carlo, Gastroenterol, Milan, Italy

来源：

JOURNAL OF HEPATOLOGY | 2019年 / 71卷 / 06期

关键词：

Retreatment; Direct-acting antivirals; Sofosbuvir; HCV; RAS; Resistance; SOFOSBUVIR-VELPATASVIR-VOXILAPREVIR; EXPERIENCED PATIENTS; VIRUS-INFECTION; RETREATMENT; THERAPY; GLECAPREVIR/PIBRENTASVIR; RIBAVIRIN; REGIMENS; NS5A;

D O I：

10.1016/j.jhep.2019.07.020

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. Methods: All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. Results: A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, la 24%, 1 nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). Conclusions: SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. Lay summary: This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxila previr (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：1106 / 1115

页数：10

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