State key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Department of Infectious Disease, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, China.
J Viral Hepat. 2019 Sep;26(9):1050-1058. doi: 10.1111/jvh.13120. Epub 2019 Jun 2.
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 (USP18 ) 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 USP18 was 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 USP18 was 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 USP18 in combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18 levels 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.
泛素特异性蛋白酶 18（USP18）是干扰素（IFN）抗病毒活性的重要抑制剂，本研究旨在探讨体外 IFN 刺激前后外周血单个核细胞（PBMC）USP18mRNA 水平变化与接受 IFN 治疗的 HBeAg 阳性慢性乙型肝炎（CHB）患者治疗结局之间的关系。共纳入 44 例接受标准 IFN 抗 HBV 治疗并随访的患者。通过比较培养有无 IFN 刺激的 BPMCs 的定量 PCR 确定的 USP18 转录水平，测量体外 IFN 诱导的 USP18mRNA 变化（USP18）。无论是病毒学（VR）还是血清学反应（SR），无反应者（VR 为 23 例，SR 为 33 例）的基线 USP18 显著高于反应者（VR 为 21 例，SR 为 11 例）（P=0.018 对于 VR，P=0.008 对于 SR）。多变量分析显示，基线 USP18 是 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）的新型独立预测因子。此外，基线 USP18 与 HBV DNA 载量或 HBeAg 水平相结合，分别显示出对 VR 或 SR 反应者的预测准确性提高。基线 USP18 水平与病毒学和血清学反应均相关，有潜力成为 HBeAg 阳性 CHB 患者在开始 IFN-α 治疗前治疗结局的临床预测因子。
