慢加急性肝衰竭的国际标准与临床管理优化

曹竹君; 张宸溪; 谢青

doi:10.3969/j.issn.1001-5256.2021.04.001

慢加急性肝衰竭的国际标准与临床管理优化

DOI: 10.3969/j.issn.1001-5256.2021.04.001

上海交通大学医学院附属瑞金医院感染科，上海 200025

基金项目:

国家自然科学基金青年项目 (82000588);

国家自然科学基金青年项目 (81900567);

十三五“科技部重大专项” (2017ZX10203201-008);

十三五“科技部重大专项” (2018ZX09201016-003-001);

十三五“科技部重大专项” (2017ZX10202202-005-004);

中国肝炎防治基金会-天晴肝病研究基金资助课题 (TQGB20210021);

上海市教育委员会和上海市教育发展基金会“晨光计划” ;

上海市临床重点专科(感染病学) (shslczdzk01103)

利益冲突声明：本文所有作者均声明不存在利益冲突。

作者贡献声明：曹竹君负责完成述评初稿撰写；张宸溪协助资料整理；谢青负责设计文章思路，初稿修订，审核及定稿。

详细信息

作者简介:
曹竹君(1990—)，男，博士，主要从事慢加急性肝衰竭的发病机制及临床管理研究

通信作者:
谢青，xieqingrjh@163.com

中图分类号: R575.3
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- 被引次数: 0
出版历程
- 收稿日期: 2021-02-28
- 录用日期: 2021-03-05
- 出版日期: 2021-04-20

Paving the way to improve clinical management of acute-on-chronic liver failure using international criteria

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Research funding:

(82000588);

(81900567);

(2017ZX10203201-008);

(2018ZX09201016-003-001);

(2017ZX10202202-005-004);

(TQGB20210021);

;

(shslczdzk01103)

摘要

摘要: 慢加急性肝衰竭(ACLF)是明显区别于急性肝衰竭和单纯肝硬化急性失代偿的一类临床群体。起病于慢性肝病基础上，急性进展可出现肝脏以及肝外多器官衰竭，短期死亡率高，已成为全球的经济卫生负担。近年来，几大国际性肝病学会提出了不同的ACLF诊断标准并相继发布了各自定义下的ACLF诊疗共识或综述，在慢性肝病、急性损伤、器官衰竭等方面的理解存在较大分歧。目前我国在ACLF管理各个关键环节，如肝移植、ICU和姑息治疗方面数据仍较为有限，在全球ACLF诊断尚未达成共识的背景下，需进一步加强国际已有标准和证据的借鉴运用以及国内循证医学证据的积累。
- 慢加急性肝功能衰竭 /
- 肝硬化 /
- 诊断 /
- 治疗学 /
- 临床管理
Abstract: Acute-on-chronic liver failure (ACLF) is a clinical disease significantly different from acute liver failure and acute decompensation of simple liver cirrhosis, and it may have acute progression to liver failure and failure of other organs. ACLF has a high short-term mortality rate and has become a disease burden worldwide. In recent years, several international associations for the study of the liver have proposed different diagnostic criteria for ACLF and published their respective consensus or review on the diagnosis and treatment of ACLF, and there are still great differences in the comprehension of chronic liver diseases, acute injury, and organ failure. At present, there are still limited data for the key links of ACLF management in China, such as liver transplantation, intensive care unit, and palliative care, and in the context of no consensus on the diagnosis of ACLF around the world, it is necessary to further strengthen the application of existing international criteria and evidence and the accumulation of evidence-based data in China.
- Acute-On-Chronic Liver Failure /
- Liver Cirrhosis /
- Diagnosis /
- Therapeutics /
- Clinical Governance

HTML全文

图 1 ACLF诊断体系中涉及的OF定义、预后评分及分层标准

注：a，APASL-2019版ACLF共识提出的ACLF预后评分^[5]；b，基于AARC的ACLF分级系统^[9]；c，欧洲学者CANONIC研究设计中基于SOFA评分修订的CLIF-SOFA评分的简化版，灰色背景的内容为各器官/系统衰竭的定义^{[2, 11]}；d，基于EASL-CLIF C ACLF诊断标准的预后评分^[11]；e，NACSELD提出的ACLF OF诊断标准^[12]。

下载: 全尺寸图片幻灯片

图 2 ACLF临床管理路径

注：a，APASL-2019版ACLF共识对于ACLF临床路径的推荐^[5]；b，欧洲学者基于CLIF C系列研究结果对基于EASL-CLIF C ACLF的临床管理路径^{[33, 39]}；c，肝硬化急性失代偿非ICU住院患者联合运用NACSELD和EASL-CLIF C ACLF的优化管理，数据来源于我国前瞻性队列，乙型肝炎病例为主，对于移植、ICU管理和姑息治疗方面的推荐尚需更多研究数据^[32]。GCSF, 粒细胞集落刺激因子；FMT, 粪菌移植；ARDS, 急性呼吸窘迫综合征。* 需要更多证据；* * 肝外OF评估依据SOFA评分；* * * ACLF-3a级为3个OFs的ACLF，ACLF-3b为4~6个OFs的ACLF。

下载: 全尺寸图片幻灯片

表 1 3大国际ACLF诊断标准特点对比

项目	APASL-AARC	EASL-CLIF C	AASLD-NACSELD
适用人群	慢性肝病或代偿期肝硬化；因肝脏直接的急性损伤，首次出现肝功能急剧恶化	代偿期或失代偿期肝硬化患者；因以下一种或多种急性失代偿事件而住院：腹水，肝性脑病，消化道大出血或急性细菌感染	代偿期或失代偿期患者；因感染入院或住院期间发生感染
排除人群	既往有失代偿史；初次失代偿但住院原因为肝硬化急性失代偿；合并细菌感染；合并肝癌患者	孕妇；因预约的操作或治疗入院；进展期肝癌；严重肝外疾病；HIV感染；正接受非重症酒精性肝炎相关的免疫抑制治疗	门诊患者；既往实体器官移植术后；恶性肿瘤转移
诱因	仅考虑肝脏诱因，如HBV再激活、酒精性肝炎、药物性肝损伤、自身免疫性肝炎发作等	同时考虑肝脏诱因和肝外诱因	仅考虑感染(属于肝外诱因)
诊断标准	慢性肝病或肝硬化代偿期，在急性肝脏打击后，出现黄疸[TBil＜5 mg/dl (85 μmol/L)]和凝血功能障碍(INR≥1.5或凝血酶原活动度＜40%)，发病4周内并发临床显性腹水和/或肝性脑病	根据EASL-CLIF C OF定义(详见图 1c)，出现2个或以上OFs，或单个肾衰竭，或单个脑衰竭合并肌酐1.5~1.9 mg/dl，或单个肝/凝血/循环或呼吸衰竭合并肌酐1.5~1.9 mg/dl和/或肝性脑病Ⅰ~Ⅱ级	根据NACSELD OF定义(详见图 1e)，出现2个或以上OFs
分层及预后 (28 d死亡率)	基于AARC评分(参见图 1) Grade-1：14.1% Grade-2：55.5% Grade-3：87.3%	基于OF数 Grade-1：20% Grade-2：30% Grade-3：80%	基于OF数 2个OFs：49% 3个OFs：64% 4个OFs：77%

下载: 导出CSV

表 2 3大国际ACLF诊断标准确诊的ACLF预后对比

第一作者及文献	APASL-AARC		EASL-CLIF C		AASLD-NACSELD		病例来源
第一作者及文献	28 d 死亡率	90 d 死亡率	28 d 死亡率	90 d 死亡率	28 d 死亡率	90 d 死亡率	病例来源
Choudhury^*[9]	40.5%	49.2%	/	/	/	/	AARC队列
Moreau^*[2]	/	/	32.8%	51.2%	/	/	CANONIC队列
O’Leary^*[13]	/	/	/	/	30 d-41.0%	/	NACSELD队列
Kulkarni^*[20]	43.8%	/	/	/	/	/	印度-ICU
Dhiman^*[21]	37.0%	/	47.4%	/	/	/	印度
Mahmud^#[22]	41.9%	56.1%	37.6%	50.4%	/	/	美国退伍军人管理局数据
Selva Rajoo^*[23]	/	35.7%	/	53.3%	/	/	新加坡
Amarapurkar^*[24]	/	43.1%	/	62.0%	/	/	印度
Shi^#[25]	/	/	49.4%	63.0%	/	/	中国
Lee^#[26]	/	/	50.4%	66.1%	/	/	韩国
Silva^*[27]	/	/	30 d-65.0%	69.9%	/	/	巴西
Picon^*[28]	/	/	61.1%	83.3%	/	/	巴西
Piano^#[29]	/	/	/	45.0%	/	/	意大利
Meersseman^#[30]	/	/	/	40.0%	/	/	比利时-ICU
Hernaez^#[31]	/	/	25.5%	40.2%	33.0%	47.5%	美国退伍军人管理局数据
Cao^*[32]	/	/	41.6%	62.9%	62.9%	94.3%	中国
注：考虑到单病因或单诱因相关的ACLF代表性较弱，因此未纳入总结。*前瞻性设计；#回顾性设计。

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