用核苷（酸）类似物完全病毒抑制后，HBsAg血清清除进一步降

StephenW

J Hepatol. 2018 Oct 24. pii: S0168-8278(18)32497-8. doi: 10.1016/j.jhep.2018.10.014. [Epub ahead of print]
HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues.
Yip TC1, Wong GL2, Chan HL2, Tse YK1, Lam KL1, Lui GC3, Wong VW4.
Author information

1
    Institute of Digestive Disease, China; Department of Medicine and Therapeutics, China.
2
    Institute of Digestive Disease, China; Department of Medicine and Therapeutics, China; State Key Laboratory of Digestive Disease, China.
3
    Department of Medicine and Therapeutics, China; Division of Infectious Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
4
    Institute of Digestive Disease, China; Department of Medicine and Therapeutics, China; State Key Laboratory of Digestive Disease, China. Electronic address: [email protected].

Abstract
BACKGROUND AND AIMS:

In treated patients with chronic hepatitis B (CHB) who have achieved complete viral suppression, it is unclear if functional cure as indicated by hepatitis B surface antigen (HBsAg) seroclearance confers additional clinical benefit. We compared the risk of hepatocellular carcinoma (HCC) and hepatic events in nucleos(t)ide analogue (NA)-treated patients with and without HBsAg seroclearance.
METHODS:

We performed a territory-wide retrospective cohort study on all CHB patients who had received entecavir and/or tenofovir disoproxil fumarate (TDF) for at least 6 months between 2005 and 2016 from Hospital Authority, Hong Kong. Patients' demographics, comorbidities, and laboratory parameters were analyzed. The primary outcome was HCC. The secondary outcomes were hepatic events including cirrhotic complications, liver transplantation, and liver-related mortality.
RESULTS:

20,263 entecavir/TDF-treated CHB patients were identified; 17,499 (86.4%) patients had complete viral suppression; 376 (2.1%) further achieved HBsAg seroclearance. At a median (interquartile range) follow-up of 4.8 (2.8-7.0) years, 603 (3.5%) and 121 (4.4%) patients with and without complete viral suppression developed HCC; 2 (0.5%) patients with HBsAg seroclearance developed HCC. Compared to complete viral suppression, lack of complete viral suppression was associated with a higher risk of HCC (7.8% vs. 5.6% at 8 years, Gray's test, P<0.001) (adjusted hazard ratio [aHR] 1.69, 95% confidence interval [CI] 1.36-2.09; P<0.001); patients who achieved functional cure had a lower risk of HCC (0.6% vs. 5.6% at 8 years, Gray's test, P<0.001) (aHR 0.24, 95% CI 0.06-0.97; P=0.045) but not hepatic events (aHR 0.99, 95% CI 0.30-3.26; P=0.991).
CONCLUSIONS:

Patients who achieved HBsAg seroclearance on top of complete viral suppression with entecavir/TDF treatment may have a lower risk of HCC but not hepatic events.
LAY SUMMARY:

We investigated 20,263 nucleos(t)ide analogue (NA)-treated patients with chronic hepatitis B. NA-induced hepatitis B surface antigen seroclearance has a lower risk of hepatocellular carcinoma but not hepatic events when compared to complete viral suppression under prolonged NA treatment.

Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
KEYWORDS:

Antiviral therapy; Cohort study; Functional cure; HBsAg seroclearance

PMID:
    30367899
DOI:
    10.1016/j.jhep.2018.10.014

StephenW

J Hepatol。 2018年10月24日.pii：S0168-8278（18）32497-8。 doi：10.1016 / j.jhep.2018.10.014。 [提前打印]
用核苷（酸）类似物完全病毒抑制后，HBsAg血清清除进一步降低了肝细胞癌的风险。
Yip TC1，Wong GL2，Chan HL2，Tse YK1，Lam KL1，Lui GC3，Wong VW4。
作者信息

1
    中国消化病研究所;中国医药与治疗学系。
2
    中国消化病研究所;中国医药与治疗学系;中国消化病国家重点实验室。
3
    中国医药与治疗学系;香港中文大学传染病科，中国香港特别行政区。
4
    中国消化病研究所;中国医药与治疗学系;中国消化病国家重点实验室。电子地址：[email protected]。

抽象
背景和目的：

在已经实现完全病毒抑制的慢性乙型肝炎（CHB）治疗患者中，尚不清楚乙型肝炎表面抗原（HBsAg）血清清除所表明的功能性治愈是否具有额外的临床益处。我们比较了有或没有HBsAg血清清除的核苷（酸）类似物（NA）治疗患者的肝细胞癌（HCC）和肝脏事件的风险。
方法：

我们对所有在2005年至2016年期间从香港医院管理局收到恩替卡韦和/或替诺福韦地索普西富马酸盐（TDF）至少6个月的CHB患者进行了全区回顾性队列研究。分析患者的人口统计学，合并症和实验室参数。主要结果是HCC。次要结果是肝脏事件，包括肝硬化并发症，肝移植和肝脏相关死亡率。
结果：

确定了20,263例恩替卡韦/ TDF治疗的CHB患者; 17499例（86.4％）患者完全病毒抑制; 376（2.1％）进一步达到HBsAg血清清除率。在4.8（2.8-7.0）岁的中位数（四分位数间）随访中，603（3.5％）和121（4.4％）患有和未完全病毒抑制的患者发生HCC; 2例（0.5％）HBsAg血清清除患者发生HCC。与完全病毒抑制相比，缺乏完全病毒抑制与较高的HCC风险相关（8年时为7.8％对比5.6％，Gray检验，P <0.001）（校正风险比[aHR] 1.69,95％置信区间[CI] 1.36-2.09; P <0.001）;达到功能性治愈的患者HCC风险较低（8年时为0.6％vs 5.6％，Gray检验，P <0.001）（aHR 0.24,95％CI 0.06-0.97; P = 0.045）但不是肝脏事件（aHR） 0.99,95％CI 0.30-3.26; P = 0.991）。
结论：

使用恩替卡韦/ TDF治疗在完全病毒抑制之上达到HBsAg血清清除率的患者可能具有较低的HCC风险但不具有肝脏事件风险。
LAY概要：

我们研究了20,263个核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者。与长期NA治疗后的完全病毒抑制相比，NA诱导的乙型肝炎表面抗原血清清除具有较低的肝细胞癌风险但不具有肝脏事件。

版权所有©2018欧洲肝脏研究协会。由Elsevier B.V.发布。保留所有权利。
关键词：

抗病毒治疗;队列研究;功能治愈; HBsAg血清清除率

结论：
    30367899
DOI：
    10.1016 / j.jhep.2018.10.014

东海以东

Compared to complete viral suppression, lack of complete viral suppression was associated with a higher risk of HCC (7.8% vs. 5.6% at 8 years, Gray's test, P<0.001)

这个概率有点高的吓人了

newchinabok

东海以东 发表于 2018-10-30 17:45
Compared to complete viral suppression, lack of complete viral suppression was associated with a hig ...

希望核衣壳抑制剂快上市，进一步降低hcc

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