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直接作用抗病毒治疗对代偿期肝硬化患者的疗效:一项多中心研究。

Efficacy of direct-acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study.

作者信息

Itokawa Norio, Atsukawa Masanori, Tsubota Akihito, Ikegami Tadashi, Shimada Noritomo, Kato Keizo, Abe Hiroshi, Okubo Tomomi, Arai Taeang, Iwashita Ai-Nakagawa, Kondo Chisa, Mikami Shigeru, Asano Toru, Matsuzaki Yasushi, Toyoda Hidenori, Kumada Takashi, Iio Etsuko, Tanaka Yasuhito, Iwakiri Katsuhiko

机构信息

Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.

出版信息

Hepatol Res. 2019 Feb;49(2):125-135. doi: 10.1111/hepr.13256. Epub 2018 Nov 13.

Abstract

AIM

Although the development of new direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection has markedly advanced, the effects of cirrhosis on DAA treatment remain unclear. We aimed to clarify the impact of cirrhosis on DAA treatment of patients infected with HCV.

METHODS

This large-scale, multicenter, retrospective study consisted of 2130 HCV genotype 1b-infected patients who were treated with one of the following DAA combination therapies: asunaprevir/daclatasvir (ASV/DCV), ledipasvir/sofosbuvir (LDV/SOF), or paritaprevir/ombitasvir/ritonavir (PTV/OBV/r). Ninety-two patients (4.3%) previously received DAA-based treatment. Seven hundred and forty-five patients (34.9%) had cirrhosis.

RESULTS

Overall, the sustained virologic response (SVR) rate was 93.0%. The SVR rates in patients who received ASV/DCV, LDV/SOF, or PTV/OBV/r were 90.0%, 96.9%, and 97.6%, respectively. The SVR rate in patients with cirrhosis (89.1%) was significantly lower than that in patients without cirrhosis (95.1%, P = 6.94 × 10 ). In the multivariate analysis for the overall cohort, absence of cirrhosis (P = 1.26 × 10 ), no previous DAA-based treatment (P = 2.54 × 10 ), low HCV-RNA levels (P = 1.64 × 10 ), wild-type non-structural protein 5A L31/Y93 (P = 7.33 × 10 ), and DAA regimen (LDV/SOF or PTV/OBV/r) (P = 1.92 × 10 ) were independent factors contributing to SVR. Except for patients with DAA-based treatment history, absence of cirrhosis (P = 2.15 × 10 ; odds ratio, 2.51) was an independent factor contributing to SVR in 2038 DAA-naïve patients.

CONCLUSION

This study suggests that the presence of cirrhosis reduces the SVR rate of DAA treatment, regardless of the type of DAA treatment.

摘要

目的

尽管用于治疗慢性丙型肝炎病毒(HCV)感染的新型直接抗病毒药物(DAA)的研发取得了显著进展,但肝硬化对DAA治疗的影响仍不明确。我们旨在阐明肝硬化对HCV感染患者DAA治疗的影响。

方法

这项大规模、多中心、回顾性研究纳入了2130例HCV基因1b型感染患者,这些患者接受了以下DAA联合疗法之一:asunaprevir/daclatasvir(ASV/DCV)、ledipasvir/sofosbuvir(LDV/SOF)或paritaprevir/ombitasvir/ritonavir(PTV/OBV/r)。92例患者(4.3%)曾接受基于DAA的治疗。745例患者(34.9%)患有肝硬化。

结果

总体而言,持续病毒学应答(SVR)率为93.0%。接受ASV/DCV、LDV/SOF或PTV/OBV/r治疗的患者的SVR率分别为90.0%、96.9%和97.6%。肝硬化患者的SVR率(89.1%)显著低于无肝硬化患者(95.1%,P = 6.94×10 )。在整个队列的多变量分析中,无肝硬化(P = 1.26×10 )、既往未接受基于DAA的治疗(P = 2.54×10 )、低HCV-RNA水平(P = 1.64×10 )、野生型非结构蛋白5A L31/Y93(P = 7.33×10 )和DAA方案(LDV/SOF或PTV/OBV/r)(P = 1.92×10 )是导致SVR的独立因素。除有基于DAA治疗史的患者外,无肝硬化(P = 2.15×10 ;比值比,2.51)是2038例初治DAA患者中导致SVR的独立因素。

结论

本研究表明,无论DAA治疗类型如何,肝硬化的存在都会降低DAA治疗的SVR率。

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