New resistance-associated substitutions and failure of dual oral therapy with daclatasvir and asunaprevir

被引：11

作者：

Mawatari, Seiichi ^{[1
]}

Oda, Kohei ^{[1
]}

Tabu, Kazuaki ^{[1
]}

Ijuin, Sho ^{[1
]}

Kumagai, Kotaro ^{[1
]}

Inada, Yukiko ^{[2
]}

Uto, Hirofumi ^{[1
,2
]}

Hiramine, Yasunari ^{[3
]}

Kure, Takeshi ^{[1
,3
]}

Fujisaki, Kunio ^{[4
]}

Hashiguchi, Masafumi ^{[1
,4
]}

Hori, Takeshi ^{[5
]}

Oshige, Akihiko ^{[1
,5
]}

Imanaka, Dai ^{[6
]}

Saishoji, Akiko ^{[1
,7
]}

Taniyama, Oki ^{[1
]}

Sakae, Haruka ^{[1
]}

Tamai, Tsutomu ^{[1
]}

Moriuchi, Akihiro ^{[1
]}

Ido, Akio ^{[1
]}

机构：

[1] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Human & Environm Sci, Digest & Lifestyle Dis, 8-35-1 Sakuragaoka, Kagoshima 8908544, Japan

[2] Miyazaki Med Ctr Hosp, Ctr Digest & Liver Dis, 2-16 Takamatsu Cho, Miyazaki 8800003, Japan

[3] Kagoshima Kouseiren Hosp, Dept Internal Med, 22-25 Tenpozan Cho, Kagoshima 8900061, Japan

[4] Kirishima Med Ctr, Dept Hepatol, 3320 Hayato Cho, Kagoshima 8995112, Japan

[5] Kagoshima City Hosp, Dept Gastroenterol & Hepatol, 37-1 Uearata Cho, Kagoshima 8908760, Japan

[6] Ikeda Hosp, Dept Gastroenteroloby, 1830 Shimoharaigawa Cho, Kagoshima 8930024, Japan

[7] Kagoshima Teishin Hosp, Dept Hepatol, 12-1 Shimoishiki, Kagoshima 8908798, Japan

来源：

JOURNAL OF GASTROENTEROLOGY | 2017年 / 52卷 / 07期

关键词：

Hepatitis C virus; Daclatasvir; Asunaprevir; NS5A resistance-associated substitutions; HEPATITIS-C VIRUS; NS5A INHIBITOR BMS-790052; INTERFERON PLUS RIBAVIRIN; GENOTYPE 1B INFECTION; TREATMENT-NAIVE; COMBINATION THERAPY; VARIANTS RESISTANT; JAPANESE PATIENTS; VIRAL LOAD; IN-VITRO;

D O I：

10.1007/s00535-016-1303-0

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background Daclatasvir (DCV) and asunaprevir (ASV) combination therapy has been primarily used in patients without NS5A L31 or Y93 resistance-associated substitutions (RASs) before treatment. We examined the characteristics of patients without these baseline RASs who did not achieve hepatitis C virus eradication with DCV and ASV combination therapy and identified new baseline NS5A RASs that are closely associated with failure of combination therapy. Methods Three hundred thirty-five patients with hepatitis C virus genotype 1 infection with no NS5A L31, NS5A Y93, and NS3 D168 RASs before DCV and ASV combination therapy and no history of protease inhibitor therapy were enrolled. All RASs were evaluated by direct sequencing. Results Sustained virologic response at 12 weeks (SVR12) was achieved in 297 patients (89%). Patients with NS5A Q24, L28, and/or R30 RASs or concomitant NS5A F37 and Q54 RASs had a significantly lower SVR12 rate than patients without these RASs (70% vs 92%, p < 0.001 and 79% vs 92%, p = 0.002 respectively). Multivariate analysis showed that NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs were significantly associated with virologic failure. The SVR12 rate in patients without NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs was 96.2% (202/210). Conclusions In patients without NS5A L31 or Y93 RASs, the presence of NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs at the baseline was associated with failure of DCV and ASV combination therapy. The coexistence of baseline RASs other than NS5A L31 and Y93 may affect the therapeutic effectiveness of DCV and ASV combination therapy.

引用

页码：855 / 867

页数：13

共 40 条

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