血清HBV RNA和乙型肝炎表面抗原水平在鑑定適合恩替卡韋治療

StephenW

Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation

    http://orcid.org/0000-0002-9012-313XWai-Kay Seto1,2,3, http://orcid.org/0000-0002-4181-8808Kevin SH Liu1, http://orcid.org/0000-0002-2266-3935Lung-Yi Mak1,2, Gavin Cloherty4, Danny Ka-Ho Wong1,2, Jeffrey Gersch4, Yuk-Fai Lam1, Ka-Shing Cheung1,3, Ning Chow1, Kwan-Lung Ko1, Wai-Pan To1, James Fung1,2, Man-Fung Yuen1,2

Author affiliations

    Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
    State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
    Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
    Infectious Disease Research, Abbott Laboratories, Abbott Park, Illinois, USA

    Correspondence to Dr Wai-Kay Seto, Medicine, University of Hong Kong, Hong Kong, China; [email protected]; Professor Man-Fung Yuen; [email protected]

Abstract

Background Treatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining treatment cessation suitability has not been well-investigated.

Methods Nucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.

Results 114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.

Conclusion Serum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.

Trial registration number NCT02738554
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http://dx.doi.org/10.1136/gutjnl-2020-321116

StephenW

血清HBV RNA和乙型肝炎表面抗原水平在鑑定適合恩替卡韋治療的亞洲慢性乙型肝炎患者中的作用

    http://orcid.org/0000-0002-9012-313XWai-Kay Seto1,2,3，http://orcid.org/0000-0002-4181-8808Kevin SH Liu1，http://orcid.org/0000 -0002-2266-3935麥龍Y1,2，加文·克洛蒂（Gavin Cloherty）4，黃宗浩（Danny Ka-Ho）1,2，杰弗裡·格施（Jeffrey Gersch）4，林玉輝1，林嘉誠1,3，寧州1，關龍Ko1，圍盼To1 ，馮檢基1,2，袁文豐1,2

作者單位

    香港大學瑪麗醫院香港大學醫學系
    香港大學肝臟研究國家重點實驗室，中國香港
    香港大學深圳醫院醫學，深圳
    美國伊利諾伊州雅培公園的雅培實驗室傳染病研究

    對應於中國香港大學醫學博士Wai-Kay Seto； [email protected];袁文峰教授； [email protected]

抽象

背景在某些乙肝表面抗原（HBsAg）血清清除之前，某些患者亞組中慢性HBV感染的治療中止可能是持久的。血清HBV RNA在確定治療中止適應性方面的作用尚未得到充分研究。

方法在非肝硬化的慢性HBV患者中，血清HBsAg <200 IU / mL，並符合國際推薦的停止治療標準，應停止使用核苷類似物（NUC）治療。監測患者至48週，並對其血清HBsAg，HBV RNA和乙肝核心相關抗原進行基線和連續測量。當HBV DNA達到> 2000 IU / mL時，無論丙氨酸轉氨酶（ALT）水平如何，都將恢復NUC。

結果招募了114例接受恩替卡韋治療的患者（中位年齡為58.4歲，中位血清HBsAg為54.4 IU / mL），中位治療時間為6。7年。 HBV DNA> 2000mLIU / mL的48週累積率為58.1％。治療結束後血清HBV RNA和非治療系列HBV RNA均與HBV DNA> 2000 IU / mL獨立相關（HR 2.959，95％CI 1.776至4.926，p <0.001; HR 2.278，95％CI 1.151至分別為4.525，p = 0.018）。 HBV RNA≥44.6U / mL的患者的48週累積率為93.2％，而將HBV RNA不可檢測性和HBsAg <10 IU / mL的患者合併使用，則48週累積率為9.1％。 24例患者（38.7％）出現了治療後ALT升高，ALT最高峰值為1515 wasU / L。 8例患者（血清HBsAg中位數為2.6 IU / mL）出現了HBsAg血清清除。

結論血清HBV RNA測定對於決定慢性乙肝患者尤其是低HBsAg水平的恩替卡韋停藥至關重要。可以根據兩種病毒決定因素對患者的治療後復發風險進行分層。

試用註冊號NCT02738554
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http://dx.doi.org/10.1136/gutjnl-2020-321116