抗病毒藥誘導的HBsAg血清清除後，停止核苷酸類似物的使用與

StephenW

Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study

    http://orcid.org/0000-0003-1850-9406Minseok Albert Kim1, http://orcid.org/0000-0002-9658-8050Seung Up Kim2, http://orcid.org/0000-0002-7126-5554Dong Hyun Sinn3, http://orcid.org/0000-0003-3255-8474Jeong Won Jang4, http://orcid.org/0000-0002-1544-577XYoung-Suk Lim5, http://orcid.org/0000-0002-3629-4624Sang Hoon Ahn2, http://orcid.org/0000-0003-2497-8663Jae-Jun Shim6, http://orcid.org/0000-0003-4171-6331Yeon Seok Seo7, http://orcid.org/0000-0002-9073-9233Yang Hyun Baek8, http://orcid.org/0000-0001-8694-777XSang Gyune Kim9, http://orcid.org/0000-0002-7113-3623Young Seok Kim9, http://orcid.org/0000-0003-3924-0434Ji Hoon Kim10, http://orcid.org/0000-0002-8019-5412Won Hyeok Choe11, http://orcid.org/0000-0002-6036-2754Hyung Joon Yim12, http://orcid.org/0000-0002-6958-3035Hyun Woong Lee13, http://orcid.org/0000-0002-5484-5864Jung Hyun Kwon14, http://orcid.org/0000-0002-5194-5130Sung Won Lee15, http://orcid.org/0000-0001-5335-752XJae Young Jang16, http://orcid.org/0000-0003-0723-1285Hwi Young Kim17, http://orcid.org/0000-0003-2560-7346Yewan Park3, http://orcid.org/0000-0002-5002-0822Gi-Ae Kim6, http://orcid.org/0000-0001-6588-9806Hyun Yang4, http://orcid.org/0000-0003-4082-1121Han Ah Lee7, http://orcid.org/0000-0002-2000-1196Myeongseok Koh8, http://orcid.org/0000-0001-6396-0859Young-Sun Lee10, http://orcid.org/0000-0002-0200-1854Minkoo Kim12, http://orcid.org/0000-0001-7752-7618Young Chang16, http://orcid.org/0000-0001-9141-7773Yoon Jun Kim1, http://orcid.org/0000-0002-9128-3610Jung-Hwan Yoon1, http://orcid.org/0000-0002-2245-0083Fabien Zoulim18, http://orcid.org/0000-0002-0315-2080Jeong-Hoon Lee1

Author affiliations
Abstract

Objective Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study.

Designs This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC).

Results During follow-up (median=26.9 months, IQR=12.2–49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38).

Conclusion The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.

StephenW

抗病毒藥誘導的HBsAg血清清除後，停止核苷酸類似物的使用與更高的HBsAg血清逆轉風險無關：一項全國性的多中心研究

    http://orcid.org/0000-0003-1850-9406Minseok Albert Kim1，http://orcid.org/0000-0002-9658-8050Seung Up Kim2，http://orcid.org/0000-0002-7126- 5554 Dong Hyun Sinn3，http://orcid.org/0000-0003-3255-8474Jeong Won Jang4，http://orcid.org/0000-0002-1544-577XYoung-Suk Lim5，http://orcid.org/0000 -0002-3629-4624 Sang Hoon Ahn2，http：//orcid.org/0000-0003-2497-8663Jae-Jun Shim6，http：//orcid.org/0000-0003-4171-6331Yeon Seo7，http：// orcid.org/0000-0002-9073-9233Yang Hyun Baek8，http：//orcid.org/0000-0001-8694-777XSang Gyune Kim9，http：//orcid.org/0000-0002-7113-3623Young Seok Kim9， http://orcid.org/0000-0003-3924-0434Ji Hoon Kim10，http：//orcid.org/0000-0002-8019-5412Won Hyeok Choe11，http：//orcid.org/0000-0002-6036- 2754 Hyung Joon Yim12，http：//orcid.org/0000-0002-6958-3035Hyun Woong Lee13，http：//orcid.org/0000-0002-5484-5864Jung Hyun Kwon14，http：//orcid.org/0000- 0002-5194-5130 Sung Won Lee15，http：//orcid.org/0000-0001-5335-752XJae Young Jang16，http：//orcid.org/0000-0003-0723-1285Hwi Young K im17，http：//orcid.org/0000-0003-2560-7346Yewan Park3，http：//orcid.org/0000-0002-5002-0822Gi-Ae Kim6，http：//orcid.org/0000-0001- 6588-9806Hyun Yang4，http：//orcid.org/0000-0003-4082-1​​121Han Ah Lee7，http：//orcid.org/0000-0002-2000-1196Myeongseok Koh8，http：//orcid.org/0000- 0001-6396-0859 Young-Sun Lee10，http：//orcid.org/0000-0002-0200-1854Minkoo Kim12，http：//orcid.org/0000-0001-7752-7618Young Chang16，http：//orcid.org / 0000-0001-9141-7773Yoon Jun Kim1，http：//orcid.org/0000-0002-9128-3610Jung-Hwan Yoon1，http：//orcid.org/0000-0002-2245-0083Fabien Zoulim18，http：/ /orcid.org/0000-0002-0315-2080Jeong-Hoon Lee1

作者單位
抽象

目的尚未對已實現HBsAg血清清除的慢性乙型肝炎患者進行核苷酸（t）ide類似物（NA）停藥與NA連續之間臨床結果的直接比較。在本研究中，研究了在NA誘導的HBV表面抗原（HBsAg）血清清除後，NA終止是否與NA連續一樣安全。

設計該多中心研究包括來自韓國16家醫院的276例患者，這些患者實現了NA誘導的HBsAg血清清除：131（47.5％）人在HBsAg血清清除後6個月內停止NA治療（NA停用組）和145例（52.5％）繼續進行NA治療（NA延續組）。主要終點是HBsAg逆轉，次要終點包括血清HBV DNA重檢測和肝細胞癌（HCC）的發展。

結果在隨訪期間（中位= 26.9個月，IQR = 12.2–49.2個月），有10例患者（3.6％）出現了HBsAg逆轉，6例（2.2％）出現了HBV DNA檢測，8例（2.9％）出現了HCC。與NA連續相比，NA中斷與單變量（HR = 0.45，95％CI = 0.12至1.76，log-rank p = 0.24）和多變量分析（校正後HR = 0.65，95％CI = 0.16）均與HBsAg逆轉無關至2.59，p = 0.54）。 NA終止組在1、3和5年HBsAg逆轉的累積概率分別為0.8％，2.3％和5.0％，而NA繼續組分別為1.5％，6.3％和8.4％。 NA終止與再次檢測HBV（HR = 0.83，95％CI = 0.16至4.16，log-rank p = 0.82）或HCC發生（HR = 0.53，95％CI = 0.12至2.23，log-等級p = 0.38）。

結論與通過NA獲得HBsAg血清清除的患者繼續進行NA相比，NA的終止與HBsAg逆轉，血清HBV DNA重新檢測或HCC發生的更高風險無關。