聚乙二醇干擾素α-2a治療HBeAg陰性慢性乙型肝炎的長期結果的

StephenW

Virological and immunological predictors of long term outcomes of peginterferon alfa-2a therapy for HBeAg-negative chronic hepatitis B
I-Cheng Lee  1 , Chien-Wei Su  1 , Keng-Hsin Lan  2 , Yuan-Jen Wang  3 , Kuei-Chuan Lee  1 , Han-Chieh Lin  1 , Ming-Chih Hou  1 , Yi-Hsiang Huang  4
Affiliations
Affiliations

    1
    Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
    2
    Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
    3
    Health Care and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.
    4
    Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: [email protected].

    PMID: 33339708 DOI: 10.1016/j.jfma.2020.12.001

Abstract

Background/purpose: Predictors of long-term outcomes of peginterferon (PegIFN) therapy for patients with chronic hepatitis B (CHB) remain to be explored. This study aimed to evaluate the predictive value of virological and immunological biomarkers and outcomes of PegIFN for CHB.

Methods: 57 HBeAg-negative CHB patients receiving 48 weeks of PegIFN therapy were prospectively followed for a median period of 5.3 years after the end of treatment (EOT). Serum CXCL9 and IP-10 levels were measured. Flow cytometry analysis for T cell subsets was performed in 23 patients. Factors associated with long-term outcomes were analyzed.

Results: The cumulative incidences of virological relapse, clinical relapse and HBsAg loss at year 7 were 18.1%, 0%, 31.6%, respectively, in patients with sustained off-treatment virological response (SVR), and 100%, 67.4%, 6.7%, respectively, in patients without SVR. By multivariate analysis, baseline CXCL9 > 80 pg/mL (hazard ratio (HR) = 0.418, p = 0.018) and on-treatment HBsAg declines were associated with a lower risk of virological relapse. Non-SVR was the only predictor of clinical relapse. CXCL9 >200 pg/mL (HR = 8.154, p = 0.038) and HBsAg <750 IU/mL (HR = 10.507, p = 0.036) were baseline predictors of HBsAg loss, while HBsAg decline >1 log at EOT (HR = 23.296, p = 0.005) was the on-treatment predictor of HBsAg loss. In subgroup patients with available PBMC, populations of T cell subsets correlated with virological and clinical relapses in univariate analysis.

Conclusion: Baseline serum CXCL9 and HBsAg levels could predict HBsAg loss after PegIFN therapy for HBeAg-negative CHB. Combining virological and immunological biomarkers could predict long-term outcomes of PegIFN therapy for HBeAg-negative CHB.

Keywords: CXCL9; Chronic hepatitis B; HBsAg loss; Peginterferon alfa-2a.

Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

StephenW

聚乙二醇干擾素α-2a治療HBeAg陰性慢性乙型肝炎的長期結果的病毒學和免疫學預測因子
李愛成1，蘇建偉1，蘭敬信2，王元仁3，李奎川1，林漢傑1，侯明治1，黃以祥4
隸屬關係
隸屬關係

    1個
    台灣台北市榮民總醫院消化內科國立陽明大學醫學院醫學院，台灣台北。
    2
    台灣台北市榮民總醫院消化內科國立陽明大學醫學院藥理研究所，台灣台北。
    3
    台灣台北市榮民總醫院衛生保健與服務中心。
    4
    台灣台北市榮民總醫院消化內科國立陽明大學醫學院醫學院，台灣台北；國立陽明大學臨床醫學研究所，台灣台北。電子地址：[email protected]。

    PMID：33339708 DOI：10.1016 / j.jfma.2020.12.001

抽象

背景/目的：聚乙二醇干擾素（PegIFN）治療慢性乙型肝炎（CHB）患者長期療效的預測指標仍有待探索。這項研究旨在評估病毒學和免疫學生物標誌物的預測價值以及PegIFN對CHB的預後。

方法：對57名接受PegIFN治療48週的HBeAg陰性CHB患者進行前瞻性隨訪，治療結束後的中位時間為5。3年（EOT）。測量血清CXCL9和IP-10水平。在23例患者中進行了T細胞亞群的流式細胞儀分析。分析了與長期預後相關的因素。

結果：持續治療後病毒學應答（SVR）患者在第7年的病毒學復發，臨床復發和HBsAg丟失的累積發生率分別為18.1％，0％，31.6％和100％，67.4％，6.7無SVR的患者分別佔％。通過多變量分析，基線CXCL9> 80 pg / mL（危險比（HR）= 0.418，p = 0.018）和治療中HBsAg下降與病毒學復發的風險較低相關。非SVR是臨床復發的唯一預測因子。 CXCL9> 200 pg / mL（HR = 8.154，p = 0.038）和HBsAg <750 IU / mL（HR = 10.507，p = 0.036）是HBsAg丟失的基線預測指標，而EOT時HBsAg下降> 1 log（HR = 23.296） ，p = 0.005）是治療中HBsAg丟失的預測指標。在具有可用PBMC的亞組患者中，單變量分析中T細胞亞群的數量與病毒學和臨床復發相關。

結論：基線血清CXCL9和HBsAg水平可以預測PegIFN治療HBeAg陰性CHB後HBsAg的丟失。結合病毒學和免疫學生物標記物可以預測PegIFN治療HBeAg陰性CHB的長期結果。

關鍵字：CXCL9;慢性乙型肝炎； HBsAg丟失；聚乙二醇干擾素α-2a。

版權所有©2020福爾摩沙醫學協會。由Elsevier B.V.發布。保留所有權利。

StephenW

https://www.sciencedirect.com/sc ... 20305982?via%3Dihub