用核苷（酸）类似物完全病毒抑制后，HBsAg血清清除进一步降

StephenW

HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues
Terry Cheuk-Fung Yip
, Grace Lai-Hung Wong
, Henry Lik-Yuen Chan
, Yee-Kit Tse
, Kelvin Long-Yan Lam
, Grace Chung-Yan Lui
, Vincent Wai-Sun Wong'Correspondence information about the author Vincent Wai-Sun WongEmail the author Vincent Wai-Sun Wong
PlumX Metrics
DOI: https://doi.org/10.1016/j.jhep.2018.10.014 |

Highlights

    •Patients without complete viral suppression have the highest risk of HCC.
    •NA-induced HBsAg seroclearance leads to lower HCC risk than complete viral suppression alone.
    •Patients with HBsAg seroclearance and complete viral suppression have a similar risk of hepatic events.

Background & 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 patients with CHB 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

A total of 20,263 entecavir/TDF-treated patients with CHB were identified; 17,499 (86.4%) patients had complete viral suppression; 376 (2.1%) 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% 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. Patients with NA-induced hepatitis B surface antigen seroclearance on top of complete viral suppression have a lower risk of hepatocellular carcinoma but not hepatic events than those only achieving complete viral suppression under prolonged NA treatment.
Keywords:
Antiviral therapy, Cohort study, Functional cure, HBsAg seroclearance

StephenW

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
Terry Cheuk-Fung Yip
，Grace Lai-Hung Wong
，Henry Lik-Yuen Chan
，Yee-Kit Tse
，Kelvin Long-Yan Lam
，Grace Chung-Yan Lui
，Vincent Wai-Sun Wong'关于作者Vincent Wai-Sun Wong的相关信息电子邮件作者Vincent Wai-Sun Wong
PlumX度量标准
DOI：https：//doi.org/10.1016/j.jhep.2018.10.014 |

强调

    •没有完全病毒抑制的患者患HCC的风险最高。
    •NA诱导的HBsAg血清清除导致HCC风险低于完全病毒抑制。
    •HBsAg血清清除和完全病毒抑制的患者具有相似的肝脏事件风险。

背景与目的

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（t）ide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CHB患者进行了一项全港性的回顾性队列研究，该患者于2005年至2016年期间从香港医院管理局接受恩替卡韦和/或替诺福韦地索普西富马酸盐（TDF）至少6个月。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

共鉴定了20,263例恩替卡韦/ TDF治疗的CHB患者; 17,499例（86.4％）患者完全病毒抑制; 376（2.1％）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％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。
放置摘要

我们调查了20,263个核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者。在完全病毒抑制的基础上，NA诱导的乙型肝炎表面抗原血清清除的患者肝细胞癌的风险低于仅肝细胞癌的风险。在长期NA治疗下实现完全病毒抑制。
关键词：
抗病毒治疗，队列研究，功能性治疗，HBsAg血清清除

StephenW

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