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韩国1b型丙型肝炎患者中与非结构蛋白5A抑制剂耐药相关变异的实际流行率及达卡他韦+阿舒瑞韦疗法的疗效

Real-life prevalence of resistance-associated variants against non-structural protein 5A inhibitors and efficiency of Daclatasvir + Asunaprevir therapy in Korean patients with genotype 1b hepatitis C.

作者信息

Yu Jung Hwan, Lee Jung Il, Lee Kwan Sik, Kim Ja Kyung

机构信息

Gangnam Severance Hospital, Department of Internal Medicine, Yonsei University College of Medicine, 20, 63-gil, Eonju-ro Gangnam-gu, Seoul, 06229, South Korea.

出版信息

Virol J. 2017 Aug 24;14(1):164. doi: 10.1186/s12985-017-0826-1.

Abstract

BACKGROUND

Direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) treatment are tolerable and highly effective in a shorter period of time than before. However, resistance-associated variants (RAVs) can affect the efficacy of DAAs. The aim of this study was to investigate the real-life prevalence of RAVs against non-structural protein 5A (NS5A) inhibitors in Korean patients with genotype 1b chronic hepatitis C.

METHODS

All consecutive patients with CHC genotype 1b who underwent a RAV test at a single referral hospital were enrolled.

RESULTS

A total of 142 patients (male 53, female 89) were tested for RAVs. The average age of the patients was 58 years. Liver cirrhosis was found in 34.5% (49/142) of patients, and 19.0% (29/142) of patients had previously undergone interferon-based treatment. Twenty-nine patients (20.4%) had RAVs (Y93 or L31). Y93H, L31, or Y93H with L31 were detected in 22 (15.5%), 8 (5.6%), and 1 (0.7%) patients, respectively. The presence of RAV was not affected by previous interferon-based treatment or by the existence of liver cirrhosis. Among 113 patients without baseline NS5A RAVs, 72 patients started daclatasvir (DCV) + asunaprevir (ASV) treatment and 95% (68/72) patients achieved virologic response at week 4. Virologic response at end of treatment and sustained virologic response at 12 weeks after treatment were achieved by 94% (68/72) and 94% (68/72), respectively.

CONCLUSIONS

In Korean patients with genotype 1b CHC, 20.4% (29 of 142) of patients showed RAVs against NS5A inhibitors. Patient without RAVs who received treatment with DCV + ASV showed high virologic response rates in Korea.

摘要

背景

用于治疗慢性丙型肝炎(CHC)的直接作用抗病毒药物(DAA)耐受性良好,且在较短时间内比以往更有效。然而,耐药相关变异(RAV)会影响DAA的疗效。本研究的目的是调查韩国1b型慢性丙型肝炎患者中针对非结构蛋白5A(NS5A)抑制剂的RAV的实际流行情况。

方法

纳入在一家转诊医院接受RAV检测的所有连续的1b型CHC患者。

结果

共对142例患者(男性53例,女性89例)进行了RAV检测。患者的平均年龄为58岁。34.5%(49/142)的患者存在肝硬化,19.0%(29/142)的患者既往接受过基于干扰素的治疗。29例患者(20.4%)存在RAV(Y93或L31)。分别在22例(15.5%)、8例(5.6%)和1例(0.7%)患者中检测到Y93H、L31或同时存在Y93H与L31。RAV的存在不受既往基于干扰素的治疗或肝硬化的影响。在113例无基线NS5A RAVs的患者中,72例患者开始接受达卡他韦(DCV)+阿舒瑞韦(ASV)治疗,95%(68/72)的患者在第4周达到病毒学应答。治疗结束时的病毒学应答率和治疗后12周的持续病毒学应答率分别为94%(68/72)和94%(68/72)。

结论

在韩国1b型CHC患者中,20.4%(142例中的29例)的患者显示出针对NS5A抑制剂的RAV。在韩国,接受DCV + ASV治疗且无RAV的患者显示出较高的病毒学应答率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6452/5571669/6ca076db86b9/12985_2017_826_Fig1_HTML.jpg

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