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丙型肝炎病毒患者中与直接抗病毒反应相关的宿主和病毒相关因素分析

Analysis of Host and Viral-Related Factors Associated to Direct Acting Antiviral Response in Hepatitis C Virus Patients.

作者信息

Aziz Hafsa, Aziz Muneeba, Gill Muzaffar Lateef

机构信息

1 Department of Diagnostic Laboratories, Nuclear Medicine Oncology and Radiotherapy Institute (NORI) , Islamabad, Pakistan .

2 Department of Digestive Diseases, Maroof International Hospital , Islamabad, Pakistan .

出版信息

Viral Immunol. 2018 Apr;31(3):256-263. doi: 10.1089/vim.2017.0124.

Abstract

Hepatitis C virus (HCV) signifies an important health issue as it is a globally prevalent pathogen and poses a great threat to human health. Direct antiviral therapy became a landmark in treatment against chronic HCV infection as they have proven to increase sustained virological response (SVR) rate, provide shortened and simplified regimens. This study aimed to evaluate efficacy of Sofosbuvir and classify factors of treatment success and their function in therapy continuation decision. We studied host and viral factors in 310 patients who received Sofosbuvir (DAA) at a dose of 400 mg daily along with ribavirin 10 mg/kg body weight for 24 weeks and followed by 12 weeks after completion of treatment. A total of 302 patients (97.42%) showed end-of-treatment response. However, 8 patients (2.58%) were virological nonresponders and 286 patients (94.70%) achieved SVR. Among 310 HCV positive, the percentage of viral genotype 3-infected patients was 89.6%, whereas only 10.32% were affected by HCV genotype 1. Multivariable analysis showed that baseline HCV RNA (≤8 × 10 IU/mL vs. >8 × 10 IU/mL) [95% confidence interval (CI), odds ratio (OR) 3.0, 2.0 to 8.4; p = 0.004], age (<50 vs. ≥50 years) (95% CI, OR 1.9, 3.0 to 10.1; p = 0.03), liver texture (normal liver vs. coarse) are related to virological response. None of the patients included in the study has S282T substitution in NS5b of HCV. No significant difference in response was observed in patients with different genotypes of rs12979860. Liver texture, age, and viral load are predictors of SVR. In this real-life data no substitution of S282T in NS5b was observed related to failure of therapy. Oral Sofosbuvir generally has a high tolerance and can effortlessly beat the safety concerns of past regimens.

摘要

丙型肝炎病毒(HCV)是一个重要的健康问题,因为它是一种全球流行的病原体,对人类健康构成巨大威胁。直接抗病毒疗法成为治疗慢性HCV感染的一个里程碑,因为它们已被证明能提高持续病毒学应答(SVR)率,提供更短且更简化的治疗方案。本研究旨在评估索磷布韦的疗效,并对治疗成功的因素及其在治疗持续决策中的作用进行分类。我们研究了310例接受索磷布韦(直接抗病毒药物)治疗的患者的宿主和病毒因素,患者每天服用400毫克索磷布韦,并联合10毫克/千克体重的利巴韦林,持续24周,治疗结束后再随访12周。共有302例患者(97.42%)显示出治疗结束时的应答。然而,8例患者(2.58%)为病毒学无应答者,286例患者(94.70%)实现了SVR。在310例HCV阳性患者中,病毒基因型3感染患者的比例为89.6%,而只有10.32%的患者受HCV基因型1影响。多变量分析显示,基线HCV RNA(≤8×10 IU/mL与>8×10 IU/mL)[95%置信区间(CI),比值比(OR)3.0,2.0至8.4;p = 0.004]、年龄(<50岁与≥50岁)(95%CI,OR 1.9,3.0至10.1;p = 0.03)、肝脏质地(正常肝脏与粗糙)与病毒学应答相关。纳入研究的患者在HCV的NS5b中均无S282T替代。在rs12979860不同基因型的患者中,未观察到应答有显著差异。肝脏质地、年龄和病毒载量是SVR的预测因素。在这些实际数据中,未观察到NS5b中的S282T替代与治疗失败有关。口服索磷布韦通常具有较高的耐受性,并且可以轻松克服过去治疗方案的安全性问题。

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