血清HBV RNA和乙型肝炎表面抗原水平在鉴定适合恩替卡韦治疗

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

    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

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鉴定适合恩替卡韦治疗的亚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麦龙Y1,2，加文·克洛蒂（Gavin Cloherty）4，黄宗浩（Danny Ka-Ho）1,2，杰弗里·格施（Jeffrey Gersch）4，林玉辉1，林嘉诚1,3，宁州1，关龙Ko1，围盼To1 ，冯检基1,2，袁文丰1,2

    对应于中国香港大学医学博士Wai-Kay Seto； [email protected];袁文峰教授； [email protected]

抽象的

背景技术在某些乙肝表面抗原（HBsAg）血清清除之前，某些患者亚组中慢性HBV感染的治疗中止可能是持久的。血清HBV RNA在确定治疗中止适应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并符合国际推荐的中止治疗标准，应停止使用核苷类似物（NUC）治疗。监测患者至48周，并对其血清HBsAg，HBV RNA和乙型肝炎核心相关抗原进行基线和连续测量。当HBV DNA达到> 2000 IU / mL时，无论丙氨酸转氨酶（ALT）水平如何，都将恢复NUC。

结果招募了114例接受恩替卡韦治疗的患者（中位年龄为58.4岁，中位血清HBsAg为54.4 IU / mL），中位治疗时间为6。7年。 HBV DNA> 2000mLIU / mL的48周累积率为58.1％。治疗结束后血清HBV RNA和非治疗系列HBV RNA均独立于HBV DNA> 2000 IU / mL（HR 2.959，95％CI 1.776至4.926，p <0.001; HR 2.278，95％CI 1.151至分别为4.525，p = 0.018）。 HBV RNA≥44.6U / mL的患者的48周累积率为93.2％，而将HBV RNA不可检测性和HBsAg <10 IU / mL的患者合并使用，则48周累积率为9.1％。 24名患者（38.7％）出现了治疗后ALT升高，ALT最高峰值为1515 U / L。 8例患者（中位血清HBsAg为2.6 IU / mL）出现HBsAg血清清除。

结论血清HBV RNA测定对于决定慢性乙肝患者尤其是低HBsAg水平的恩替卡韦停药至关重要。可以根据两个病毒决定因素对患者进行治疗后复发的风险进行分层。

试用注册号NCT02738554

http://dx.doi.org/10.1136/gutjnl-2020-321116