血清角蛋白-18片段作为细胞死亡生物标志物与HBV相关性肝硬

StephenW

J Viral Hepat. 2019 Apr 11. doi: 10.1111/jvh.13100. [Epub ahead of print]
Serum keratin-18 fragments as cell death biomarker in association with disease progression and prognosis in HBV-related cirrhosis.
Cao Z1, Chen L1, Li J2, Liu Y1, Bao R3, Liu K1, Yan L1, Ding Y1, Guo Q1, Xiang X1, Xie J1, Lin L1, Xie Q1, Bao S4, Wang H1.
Author information

1
    Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2
    Department of Infectious Diseases, Huai-An Fourth People's Hospital, Jiangsu, 223002, China.
3
    Discipline of Anatomy and Histology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW, 2006, Australia.
4
    Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW, 2006, Australia.

Abstract

Extensive hepatocyte death leads to hepatic inflammation and contributes to systemic inflammation in decompensated cirrhosis. We aimed to investigate the prognostic value of serum cell death markers in patients with Hepatitis B virus (HBV)-related acute decompensation (AD) of cirrhosis with and without acute-on-chronic liver failure (ACLF). We studied two cohorts - cohort 1: 201 outpatients with stable chronic hepatitis B (49 cirrhosis); cohort 2: 232 inpatients with HBV-related cirrhosis admitted for AD. Cell death was determined with serum Keratin-18 (K18) for total death and serum caspase-cleaved-K18 (cK18) for apoptosis. Survival analyses were performed using competing risk method. We found that serum K18 and cK18 were significantly (p<0.001) higher in patients from cohort 2 than those from cohort 1. Among cohort 2, ACLF patients had significantly (p<0.001) increased K18 and cK18 comparing to those without ACLF. Increased K18 and cK18 were mainly attributed to HBV flare and were associated with liver and coagulation failure. HBV-AD patients without ACLF who admitted with upper-tertile of K18 or cK18 were at higher risk of developing ACLF during follow-up. Baseline serum K18 or cK18 was significantly associated with transplant-free 90-day survival independent of leukocytes, HBV DNA, bacterial infection, encephalopathy and severity scores. The combination of cell death biomarkers significantly improved the prognostic value of the currently established prognostic scores. The reduction of cell death level after standard treatment was associated with increased short-term survival. In conclusion measurements of serum K18 or cK18 in HBV decompensated cirrhosis is a promising tool for predicting ACLF and risk stratification of short-term outcome. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

Acute-on-chronic liver failure; Apoptosis; Decompensated cirrhosis; Hepatitis B virus; Necrosis; Prognosis

PMID:
    30974482
DOI:
    10.1111/jvh.13100

StephenW

J病毒肝病。 2019年4月11日doi：10.1111 / jvh.13100。 [印刷前的电子版]
血清角蛋白-18片段作为细胞死亡生物标志物与HBV相关性肝硬化的疾病进展和预后相关。
Cao Z1，Chen L1，Li J2，Liu Y1，Bao R3，Liu K1，Yan L1，Ding Y1，Guo Q1，Xiang X1，Xie J1，Lin L1，Xie Q1，Bao S4，Wang H1。
作者信息

1
    上海交通大学医学院附属瑞金医院感染科，上海200025
2
    淮安市第四人民医院感染科，江苏，223002
3
    解剖学和组织学学科，悉尼大学医学院和博世研究所，悉尼，新南威尔士州，2006年，澳大利亚。
4
    悉尼大学医学院和博世学院病理学学科，悉尼，新南威尔士州，2006年，澳大利亚。

抽象

广泛的肝细胞死亡导致肝脏炎症并且导致失代偿性肝硬化中的全身性炎症。我们的目的是调查血清细胞死亡标志物对乙型肝炎病毒（HBV）相关的肝硬化急性失代偿（AD）伴有和不伴有急性慢性肝衰竭（ACLF）的患者的预后价值。我们研究了两个队列 - 队列1：201门诊患有稳定的慢性乙型肝炎（49例肝硬化）;队列2：232住院患有HBV相关性肝硬化的住院患者。用血清角蛋白-18（K18）测定细胞死亡的总死亡率，用血清半胱天冬酶切割的-K18（cK18）测定细胞凋亡。使用竞争风险方法进行生存分析。我们发现组群2患者的血清K18和cK18显着（p <0.001）高于组群1的患者。在组群2中，与没有ACLF的患者相比，ACLF患者的K18和cK18显着增加（p <0.001）。增加的K18和cK18主要归因于HBV眩光，并且与肝脏和凝血功能衰竭有关。接受K18或cK18上三分位的无ACLF的HBV-AD患者在随访期间发生ACLF的风险较高。基线血清K18或cK18与无移植90天存活率显着相关，不依赖于白细胞，HBV DNA，细菌感染，脑病和严重程度评分。细胞死亡生物标志物的组合显着改善了目前建立的预后评分的预后价值。标准治疗后细胞死亡水平的降低与短期存活率的增加有关。总之，HBV失代偿期肝硬化患者血清K18或cK18的测量结果是预测ACLF和短期预后危险分层的有效工具。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

急性慢性肝功能衰竭;细胞凋亡;失代偿性肝硬化;乙型肝炎病毒;坏死;预测

结论：
    30974482
DOI：
    10.1111 / jvh.13100