慢性乙型肝炎患者血清乙型肝炎核心相关抗原对肝纤维化的

StephenW

World J Gastroenterol. 2019 Aug 28;25(32):4764-4778. doi: 10.3748/wjg.v25.i32.4764.
On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B.
Chang XJ1, Sun C2, Chen Y3, Li XD4, Yu ZJ5, Dong Z3, Bai WL3, Wang XD6, Li ZQ5, Chen D7, Du WJ8, Liao H9, Jiang QY4, Sun LJ4, Li YY3, Zhang CH4, Xu DP4, Chen YP6, Li Q7, Yang YP1.
Author information

1
    Chinese PLA Medical School, Chinese PLA General Hospital, Beijing 100853, China.
2
    Peking University 302 Clinical Medical School, Beijing 100039, China.
3
    Department of Therapeutic Research for Liver Cancer, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
4
    Department of Research for Clinical Medicine, the Fifth Medical center of Chinese PLA General Hospital, Beijing 100039, China.
5
    Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
6
    Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
7
    Fuzhou Infectious Diseases Hospital, Fuzhou 350025, Fujian Province, China.
8
    Medical Department Training Graduate Office, Chinese PLA General Hospital, Beijing 100853, China.
9
    Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.

Abstract
BACKGROUND:

Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.
AIM:

To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.
METHODS:

This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.
RESULTS:

Level of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.
CONCLUSION:

HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.
KEYWORDS:

Cirrhosis; Hepatitis B core-related antigen; Liver fibrosis; On-treatment monitoring

PMID:
    31528100
PMCID:
    PMC6718032
DOI:
    10.3748/wjg.v25.i32.4764

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StephenW

World J Gastroenterol。 2019年8月28日; 25（32）：4764-4778。 doi：10.3748 / wjg.v25.i32.4764。
慢性乙型肝炎患者血清乙型肝炎核心相关抗原对肝纤维化的治疗监测
Chang XJ1，Sun C2，Chen Y3，Li XD4，Yu ZJ5，Dong Z3，Bai WL3，Wang XD6，Li ZQ5，Chen D7，Du WJ8，廖H9，Jiang QY4，Sun LJ4，Li YY3，Zhang CH4，Xu DP4 ，陈YP6，李Q7，杨YP1。
作者信息

1
    中国人民解放军总医院解放军医学院，北京100853
2
    北京大学302临床医学院，北京100039
3
    中国人民解放军总医院第五医疗中心肝癌治疗研究室，北京100039
4
    中国人民解放军总医院第五医疗中心临床医学研究室，北京100039
五
    郑州大学第一附属医院感染科，河南郑州450052
6
    温州医科大学附属第一医院肝病研究中心传染病与肝病科，浙江温州325000。
7
    福州市福州市传染病医院，福建省福州市350025
8
    中国人民解放军总医院医务科培训研究室，北京100853
9
    北京大学健康科学中心基础医学学院微生物与传染病中心，北京100191

抽象
背景：

肝纤维化的非侵入性评估在临床上很重要，特别是在用核苷类似物治疗无法检测到的乙型肝炎病毒（HBV）DNA的患者中。
目标：

为了阐明乙肝核心相关抗原（HBcrAg）对恩替卡韦治疗的慢性乙型肝炎（CHB）患者肝组织学变化的监测能力。
方法：

这项前瞻性多中心研究分别对403名CHB患者进行了多序数和多变量物流回归分析，以评估与Ishak纤维化评分和回归相关的变量，其中374例接受恩替卡韦治疗72周（291例行了肝活检配对），其中29例进行了控制。
结果：

乙肝e抗原（HBeAg）阳性患者的HBcrAg水平与肝纤维化分期呈负相关（γ= -0.357，P <0.001），而HBeAg阴性患者的HBcrAg水平与肝纤维化分期呈正相关。较高的HBcrAg浓度与年龄较小，HBeAg阳性状态，较高的HBV DNA载量，较高的乙型肝炎表面抗原（HBsAg）水平和较高的坏死性炎症有关，但与HBV基因型无关。血清HBcrAg浓度，基础核心启动子/前核心（BCP / PC）突变体，HBsAg定量（qHBsAg）和血小板计数与多次排序回归的Ishak纤维化评分独立相关。在第72周接受恩替卡韦治疗的患者中，未检测到HBV DNA的比例为88.37％，但仍可检测到其HBcrAg的水平。治疗后HBcrAg浓度的降低与肝纤维化的消退和组织学改善有关。基线时HBcrAg浓度> 6.33 log IU / mL，第72周对数减少> 1.03 log IU / mL与肝纤维化消退和组织学改善的机会分别较高。
结论：

HBcrAg水平与肝纤维化进展相关。 HBcrAg是肝脏组织学变化的优秀监测，特别是在用核苷类似物治疗的CHB患者中。
关键词：

肝硬化;乙肝核心相关抗原；肝纤维化；治疗中监测

结论：
    31528100
PMCID：
    PMC6718032
DOI：
    10.3748 / wjg.v25.i32.4764

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StephenW

https://www.wjgnet.com/1007-9327/full/v25/i32/4764.htm