Transcriptional response of USP18 predicts treatment outcomes of interferon-alpha in HBeAg-positive chronic hepatitis B patientsefere
Transcriptional response of USP18 predicts treatment outcomes of interferon-alpha in HBeAg-positive chronic hepatitis B patientsefere
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USP18 的转录反应可预测 HBeAg 阳性慢性乙型肝炎患者干扰素 α 的治疗结果
DOI：
10.1111/jvh.13120
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发表时间：
2019
影响因子：
2.5
通讯作者：
Xia Ningshao
中科院分区：
文献类型：
--
作者：
Liu Wei;Liang Huiqing;Wang Shaojuan;Wu Chuncheng;Liu Yang;Liu Yongliang;Zhang Manying;Xiong Lixia;Zhong Zhouyue;Chen Yue;Mao Qianguo;Ge Shengxiang;Xia Ningshao
泛素特异性蛋白酶18（USP 18）是干扰素（IFN）抗病毒活性的重要抑制剂，本研究的目的是研究开始治疗前用IFN体外刺激时外周血单核细胞（PBMC）中USP 18 mRNA水平变化与HBeAg阳性慢性B肝炎（CH B）患者接受IFN治疗的治疗结局之间的关系。共有44名接受标准基于干扰素的抗乙型肝炎病毒治疗和随访的患者入组了该研究。通过比较有和无IFN刺激培养的BPMC的定量PCR测定的USP 18转录水平，测量体外IFN诱导的USP 18 mRNA变化（USP 18 IFN-N）。对于病毒学（VR）或血清学应答（SR），无应答者（VR n = 23，SR n = 33）的基线USP 18 IFN-N显著高于应答者（VR n = 21，SR n = 11）（VR P= 0.018，SR P= 0.008）。多变量分析显示基线USP 18 IFN-N是本队列中VR（OR = 0.292，95%CI = 0.102 - 0.835，P = 0.022）或SR（OR = 0.173，95%CI = 0.035 - 0.849，P = 0.031）的新的独立预测因子。此外，基线USP 18 IFN-γ联合HBV DNA载量或HBeAg水平分别显示VR或SR应答者治疗前预测的准确性提高。基线USP 18 IFN-N水平与病毒学和血清学应答相关，并有可能成为开始IFN-α治疗前HBeAg阳性CHB患者治疗结局的临床预测因子。
Ubiquitin‐specific protease 18 (USP18) is an important inhibitor of interferon (IFN) antiviral activity, and the aim of this study was to investigate the association between the USP18 mRNA level change in peripheral blood mononuclear cells (PBMCs) when stimulated with IFN in vitro before initiating treatment and the treatment outcomes in HBeAg‐positive chronic hepatitis B (CHB) patients treated with IFN. A total of 44 patients who received standard IFN‐based anti‐HBV therapy and follow‐up were enrolled in the study. The in vitro IFN‐induced USP18 mRNA change (USP18IFN‐N) was measured via comparison of quantitative PCR‐determined USP18 transcription levels of BPMCs cultured with and without IFN stimulation. Either for virological (VR) or serological response (SR), the baseline USP18IFN‐Nwas significantly higher (P= 0.018 for VR,P= 0.008 for SR) among nonresponders (n = 23 for VR, n = 33 for SR) than that of responders (n = 21 for VR, n = 11 for SR). Multivariate analyses revealed baseline USP18IFN‐Nwas a novel independent predictor for either VR (OR = 0.292, 95% CI = 0.102‐0.835,P= 0.022) or SR (OR = 0.173, 95% CI = 0.035‐0.849,P= 0.031) in our cohort. In addition, baseline USP18IFN‐Nin combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18IFN‐Nlevels are associated with both virological and serological response, and have the potential to become a clinical predictor for treatment outcomes in HBeAg‐positive CHB patients before initiating IFN‐α therapy.