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Transcriptional response of USP18 predicts treatment outcomes of interferon‐alpha in HBeAg‐positive chronic hepatitis B patientsefere
Author(s) -
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
Publication year - 2019
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.13120
Subject(s) - peripheral blood mononuclear cell , medicine , hbeag , interferon , alpha interferon , immunology , chronic hepatitis , serology , gastroenterology , virology , in vitro , hepatitis b virus , biology , virus , antibody , hbsag , biochemistry
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 IFN‐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 USP18 IFN‐N 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 IFN‐N 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 IFN‐N in combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18 IFN‐N 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.