恩替卡韦治疗的HBeAg阳性慢性乙型肝炎的病毒学突破与临床结

StephenW

PLoS One. 2019 Aug 30;14(8):e0221958. doi: 10.1371/journal.pone.0221958. eCollection 2019.
Association of virological breakthrough and clinical outcomes in entecavir-treated HBeAg-positive chronic hepatitis B.
Huang YJ1, Yang SS1,2, Yeh HZ1,3, Chang CS1,2, Peng YC1,3,4.
Author information

1
    Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
2
    School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
3
    School of Medicine, National Yang-Ming University, Taipei, Taiwan.
4
    Department of Internal Medicine, Chiayi branch of Taichung Veterans General Hospital, Chiayi, Taiwan.

Abstract
BACKGROUND & AIMS:

To evaluate virological breakthrough (VBT) and the risk of hepatocellular carcinoma (HCC) in HBeAg-positive chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment.
METHODS:

A retrospective cohort study was conducted in a tertiary referral hospital and a total of 228 HBeAg-positive CHB patients treated with ETV for more than 48 weeks were enrolled. Clinical outcome measures included HBeAg seroclearance, maintained virological response and the development of HCC.
RESULTS:

During a median follow-up period of 197 weeks, VBT developed in 26 (11.4%) patients (VBT group), and the other 202 patients without VBT (non-VBT group). The overall cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group were 23.1% and 23.8%, 27.1% and 37.9%, 27.1% and 55.1%, 27.1% and 74.1%, 27.1% and 76.7% from week 48 to 240, respectively(p = 0.013). The cumulative probability of maintained virological responses from week 48 to 240 were 7.69% and 21.78%, 7.69% in the VBT groups and 36.85%, 7.69% and 51.68%, 7.69% and 64.97%, 7.69% and 72.1% in the non-VBT groups, respectively (p<0.001). In the multivariate analysis, age (p<0.001) and virological response at week 24 (p = 0.005) were independently associated with VBT. Cox regression analysis showed that cirrhosis had carried the highest risk for HCC (HR = 4.99, CI = 1.14-21.81, p = 0.033). Subgroup survival analysis by Kaplan-Meier method showed that patients with VBT had higher incidence of developing HCC than without VBT in cirrhotic patients (50% (95%CI = 1-99%) vs 9% (95% CI = 1-9%); p = 0.048).
CONCLUSIONS:

VBT was associated with adverse clinical outcomes, including a low probability of HBeAg seroclearance, failure to achieve maintained virological responses, and a risk of developing HCC. Patients, particularly with cirrhosis, who had experienced VBT during ETV treatment, more likely developed HCC.

PMID:
    31469875
DOI:
    10.1371/journal.pone.0221958

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StephenW

PLoS One。 2019年8月30日; 14（8）：e0221958。 doi：10.1371 / journal.pone.0221958。 eCollection 2019。
恩替卡韦治疗的HBeAg阳性慢性乙型肝炎的病毒学突破与临床结果的关联
Huang YJ1，Yang SS1,2，Yeh HZ1,3，Chang CS1,2，Peng YC1,3,4。
作者信息

1
    台湾台中市台中退伍军人总医院内科，消化内科。
2
    台湾台中市中山医科大学医学院。
3
    台湾台北国立阳明大学医学院。
4
    台湾嘉义市台中退伍军人总医院嘉义分院内科

抽象
背景与目的：

评估接受恩替卡韦（ETV）治疗的HBeAg阳性慢性乙型肝炎（CHB）患者的病毒学突破（VBT）和肝细胞癌（HCC）风险。
方法：

一项回顾性队列研究在三级转诊医院进行，共有228名接受ETV治疗超过48周的HBeAg阳性CHB患者入组。临床结果测量包括HBeAg血清清除，维持病毒学应答和HCC的发展。
结果：

在197周的中位随访期间，VBT在26名（11.4％）患者（VBT组）中发展，另外202名患者在没有VBT（非VBT组）的情况下发展。从第48周开始，VBT组和非VBT组HBeAg血清清除率的总累积率分别为23.1％和23.8％，27.1％和37.9％，27.1％和55.1％，27.1％和74.1％，27.1％和76.7％。分别为240（p = 0.013）。从第48周到第240周维持病毒学应答的累积概率分别为7.69％和21.78％，VBT组为7.69％，非非洲分别为36.85％，7.69％和51.68％，7.69％和64.97％，7.69％和72.1％。 VBT组分别（p <0.001）。在多变量分析中，年龄（p <0.001）和第24周的病毒学应答（p = 0.005）与VBT独立相关。 Cox回归分析显示肝硬化患HCC的风险最高（HR = 4.99，CI = 1.14-21.81，p = 0.033）。 Kaplan-Meier法分组生存分析显示，肝硬化患者VBT发生HCC的发生率高于无肝硬化患者（50％（95％CI = 1-99％）vs 9％（95％CI = 1-9％） ）;; p = 0.048）。
结论：

VBT与不良临床结果相关，包括HBeAg血清清除率低，未能维持病毒学应答，以及发生HCC的风险。在ETV治疗期间经历过VBT的患者，尤其是肝硬化患者，更可能患有HCC。

结论：
    31469875
DOI：
    10.1371 / journal.pone.0221958

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StephenW

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