HBeAg血清清除后肝细胞癌和HBsAg血清清除的长期结果和预测评

StephenW

Hepatology. 2018 Mar 13. doi: 10.1002/hep.29874. [Epub ahead of print]
Long Term Outcomes and Predictive Scores for Hepatocellular Carcinoma and HBsAg Seroclearance after HBeAg Seroclearance.Fung J1,2, Cheung KS1, Wong DK1,2, Mak LY1, To WP1, Seto WK1,2, Lai CL1,2, Yuen MF1,2.
Author information
1Department of Medicine, The University of Hong Kong, Hong Kong, SAR.2State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, SAR.

AbstractThe significance of hepatitis B e-antigen seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive scores for hepatocellular carcinoma (HCC) and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3-6 monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC-ESC) and HBsAg seroclearance (HBsAg-ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow-up of 36.0 and 18.3 years respectively. Only 3.5% and 3.0% had persistently normal ALT and HBV DNA <2logs IU/mL respectively after ESC. For patients with 100%, 100-90%, 90-50%, 50-10%, 10-0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC respectively (p<0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5% respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The AUROC for HCC-ESC and HBsAg-ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74 respectively.
CONCLUSIONS: Male gender, older age at ESC, ALT, and higher level of HBV DNA were associated with higher rates of HCC after ESC. HCC-ESC and HBsAg-ESC predictive scores can determine the likelihood of developing HCC and achieving HBsAg seroclearance. This article is protected by copyright. All rights reserved.

© 2018 by the American Association for the Study of Liver Diseases.

KEYWORDS: antigen; chronic hepatitis B; prognosis; seroconversion; viral

PMID:29534307DOI:10.1002/hep.29874

StephenW

肝病。 2018年3月13日，doi：10.1002 / hep.29874。 [电子版提前打印]
HBeAg血清清除后肝细胞癌和HBsAg血清清除的长期结果和预测评分。
Fung J1,2，Cheung KS1，Wong DK1,2，Mak LY1，To WP1，Seto WK1,2，Lai CL1,2，Yuen MF1,2。
作者信息

1
    香港大学医学系香港特区。
2
    香港大学肝脏研究国家重点实验室，香港特别行政区。

抽象

乙型肝炎e抗原血清清除（ESC）的长期意义尚不明确。目前的研究旨在确定ESC患者的大批患者的肝细胞癌（HCC）和乙型肝炎表面抗原（HBsAg）血清学清除的临床结果，因素和预测评分。记录ESC的患者每月随访3-6个月。记录基线特征和纵向实验室结果。 HCC（HCC-ESC）和HBsAg血清清除率（HBsAg-ESC）的预测评分来自多变量Cox回归模型。共有723名患者接受了ESC，ESC年龄中位数分别为36.0和18.3岁。 ESC后ALT和HBV DNA分别仅持续3.5％和3.0％，持续正常ALT水平<2log IU / mL。对于HBeAg血清学清除后100％，100-90％，90-50％，50-10％，10-0％和0％ALT正常的患者，HCC率分别为4.3％，2.2％，3.6％，3.9 ％，17.3％和37.2％（P <0.001）。在ESC 20年后，HCC和HBsAg血清学清除的累计发生率分别为7.9％和13.5％，总生存率为91.5％。 ESC年龄，男性，肝硬化，低白蛋白血症，病毒载量和ALT是HCC的重要因素，而ESC年龄，男性，病毒载量和抗病毒治疗是HBsAg血清学清除的重要因素。 ESC后HCC-ESC和HBsAg-ESC评分可预测HCC和HBsAg血清学清除率，ESC分别为0.92和0.74。
结论：

男性，ESC年龄较大，ALT和HBV DNA水平较高与ESC后HCC发生率较高有关。 HCC-ESC和HBsAg-ESC预测评分可以确定发生HCC并实现HBsAg血清学清除的可能性。本文受版权保护。版权所有。

©美国肝病研究协会版权所有©2018年。
关键词：

抗原;慢性乙型肝炎;预后;血清转化;病毒

结论：
    29534307
DOI：
    10.1002 / hep.29874

StephenW

Abnormal ALT after HBeAg seroclearance increases liver cancer risk

Fung J, et al. Hepatol. 2018;doi:10.1002/hep.29874.
March 16, 2018

Patients with hepatitis B had a higher risk for hepatocellular carcinoma after HBV e antigen seroclearance if they were men, had higher levels of HBV DNA, were unable to achieve normalized alanine aminotransferase levels, and were older at the time of HBeAg seroclearance, according to a recently published study.

“Those with persistently normal ALT after [HBeAg seroclearance] had a much more favorable outcome, including a low rate of HCC development, high rate of [HBV surface antigen (HBsAg)] seroclearance, and low liver-related mortality,” James Fung, MD, from the University of Hong Kong, and colleagues wrote. “This highlights the importance of viral suppression with normalization of ALT.”


Fung and colleagues followed 723 patients with HBV who achieved HBeAg seroclearance. Median age at HBeAg seroclearance was 36 years (range, 19-85 years) and median follow-up was 18.3 years (range, 2.8-32.9 years).

After HBeAg seroclearance, 3.5% of patients achieved completely normal ALT and 10.1% had normalized ALT during 90% or more of follow-up. Another 10.1% had persistently elevated ALT, 19.4% of whom had abnormal ALT during 90% or more of follow-up.

The rate of HCC was 4.3% among patients with persistently normal ALT after HBeAg seroclearance, 2.2% among those with normal ALT for 90% to 100% of follow-up, and continued to increase up to 17.3% among those with normal ALT for 10% or less of follow-up, and 37.2% for those who did not achieve normalized ALT (P < .001).

At 20 years follow-up after HBeAg seroclearance, the HCC rate was 11% for those with HBV DNA higher than 4 log IU/mL and 1.2% for those with HBV DNA less than 4 log IU/mL, whereas no patients with HBV DNA less than 3 log IU/mL developed HCC (P = .006).

Multivariate analysis showed that age at HBeAg seroclearance (HR = 1.06; 95% CI, 1.03-1.1), male sex (HR = 3.39; 95% CI, 1.22-9.41), cirrhosis (HR = 6.07; 95% CI, 2.55-14.43), hypoalbuminemia (HR = 4.1; 95% CI, 1.53-10.96), HBV DNA (HR = 1.33; 95% CI, 1.01-1.73) and ALT flares or persistently abnormal ALT (HR = 6.77; 95% CI, 1.98-23.2) were significant factors for HCC development after HBeAg seroclearance.

Additionally, the researchers found the rate of HBsAg seroclearance was 79.4% among patients with persistently normal ALT after HBeAg seroclearance, 25.9% among those with normal ALT for 90% to 100% of follow-up, and continued to decrease to 0% among those with normal ALT for up to 10% of follow-up, and 1.8% among those with persistently abnormal ALT (P < .01).

Multivariate analysis showed that age at HBeAg seroclearance (HR = 1.05; 95% CI, 1.01-1.09), male sex (HR = 2.03; 95% CI, 1.02-4.03), viral load (HR = 0.75; 95% CI, 0.61-0.92), and history of antiviral therapy (HR = 0.15; 95% CI, 0.4-0.51) were significant factors associated with HBsAg seroclearance. – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

StephenW

HBeAg血清清除后ALT异常增加肝癌风险

Fung J等人肝脏病。 2018; DOI：10.1002 / hep.29874。
2018年3月16日

根据一项研究，如果乙肝患者是男性，乙肝病毒DNA水平较高，不能达到标准化的丙氨酸转氨酶水平，并且在HBeAg血清学清醒时年龄较大，则乙肝患者在接受乙肝e抗原血清学清除后发生肝细胞癌的风险较高最近发表的研究。

“HBeAg血清清除后持续ALT正常的患者有更好的结果，包括HCC发展率低，[HBV表面抗原（HBsAg）]清除率高，肝脏相关死亡率低，”James Fung，香港大学医学博士及其同事写道。 “这突出显示了ALT正常化后病毒抑制的重要性。”


Fung及其同事跟踪了723名获得HBeAg血清学清除的HBV患者。 HBeAg血清清除率的中位年龄为36岁（范围19-85岁），中位随访时间为18.3岁（范围2.8-32.9岁）。

HBeAg血清学清除后，3.5％的患者达到完全正常的ALT，10.1％的患者在90％或更多的随访期间ALT正常。另有10.1％的患者ALT持续升高，其中19.4％在随访90％或以上时ALT异常。

HBeAg血清学清除后ALT持续正常的患者中HCC率为4.3％，ALT正常者为90％〜100％随访中为2.2％，ALT正常者为10％持续增加至17.3％ ％以下的随访，未达到正常ALT的患者为37.2％（P <.001）。

在HBeAg血清学清除后的20年随访中，HBV DNA高于4 log IU / mL的患者的HCC率为11％，HBV DNA低于4 log IU / mL的患者的HCC率为1.2％，而没有HBV DNA的患者小于3 log IU / mL发展为HCC（P = .006）。

多因素分析显示，HBeAg血清清除率（HR = 1.06; 95％CI，1.03-1.1），男性（HR = 3.39; 95％CI，1.22-9.41），肝硬化（HR = 6.07; 95％CI，2.55- 14.43），低白蛋白血症（HR = 4.1; 95％CI，1.53-10.96），HBV DNA（HR = 1.33; 95％CI，1.01-1.73）和ALT波动或ALT持续异常（HR = 6.77; 95％CI，1.98 -23.2）是HBeAg血清清除后HCC发生的重要因素。

此外，研究人员发现HBeAg血清学清除后ALT持续正常的患者HBsAg血清清除率为79.4％，ALT正常者为90％〜100％，随访中继续降低至0％正常ALT高达10％的随访，ALT持续异常的患者为1.8％（P <0.01）。

多变量分析显示，HBeAg血清清除率（HR = 1.05; 95％CI，1.01-1.09），男性（HR = 2.03; 95％CI，1.02-4.03），病毒载量（HR = 0.75; 95％CI， -0.92）和抗病毒治疗史（HR = 0.15; 95％CI，0.4-0.51）是与HBsAg血清清除有关的重要因素。 - 通过Talitha Bennett

披露：作者报告没有相关的财务披露。

纠结哥哥

回复 StephenW 的帖子

看不懂 就是大三阳转为小三阳后更危险?

纠结哥哥

回复 StephenW 的帖子

我有点肝损了 每次B超都是 表面欠光滑 回声增粗增强  结论 慢性肝病。 抗病毒前大三阳 E抗原17  替诺六个月后，转为小三阳。 这样是不是更危险? 怎么办? 还有 原来恩替抗病毒时 转氨酶为20，换替诺后 转氨酶谷丙48 谷草38 升高了不少

StephenW

回复 纠结哥哥 的帖子

不是.

“HBeAg血清清除[大三阳转为小三阳]后持续ALT正常的患者有更好的结果，包括HCC发展率低，[HBV表面抗原（HBsAg）]清除率高，肝脏相关死亡率低，”James Fung，香港大学医学博士及其同事写道。 “这突出显示了病毒抑制后ALT正常化的重要性。”

StephenW

回复 纠结哥哥 的帖子

替诺六个月后，转为小三阳。 这样是不是更危险? 不是
还有 原来恩替抗病毒时 转氨酶为20，换替诺后 转氨酶谷丙48 谷草38 升高了不少 - 为什么换替诺?
恩替或替诺治疗后, 转氨酶应该正常化 (< 30 iu/l 男性).
换替诺后, 病毒载量是？

纠结哥哥

回复 StephenW 的帖子

病毒小于20, 因为要二胎 医生说换替诺

StephenW

回复 纠结哥哥 的帖子

你是男性还是女性?

如果是男性, 无需换.
病毒小于20, 转氨酶谷丙48不是由于乙肝. 转氨酶谷丙测试前你做过剧烈运动吗？