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慢加急性肝衰竭前期的研究现状
DOI: 10.12449/JCH260206
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：赵睿负责设计论文框架，数据收集，分析资料，撰写论文；焦婧然负责绘制图表，修改论文；陈煜负责拟定写作思路，指导撰写文章并最后定稿。
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摘要: 慢加急性肝衰竭（ACLF）是一种在慢性肝病基础上由急性诱因引发的高病死率综合征，临床发现ACLF具有一定可逆性，早期干预可改善预后，延误诊治则显著增加病死率。近年来，领域内学者提出“ACLF前期”（Pre-ACLF）概念，旨在通过早期识别和干预改善临床结局。本文系统回顾了Pre-ACLF的概念起源及国内外的最新定义，总结了Pre-ACLF研究中传统临床-实验室指标、高通量组学和分子生物学机制的最新进展；并提出需进一步统一Pre-ACLF定义的重要临床需求。Abstract: Acute-on-chronic liver failure （ACLF） is a syndrome with high mortality triggered by acute predisposing factors in patients with underlying chronic liver diseases. Clinical studies have shown that ACLF can be reversed to a certain degree， and early intervention can improve patient prognosis， whereas delayed diagnosis and treatment can lead to a significant increase in mortality. In recent years， scholars in this field have proposed the concept of “pre-acute-on-chronic liver failure （Pre-ACLF）”， which aims to improve clinical outcomes through early identification and intervention. This article systematically reviews the origin of the Pre-ACLF concept and its latest definitions in China and globally， summarizes the latest research advances in Pre-ACLF in terms of traditional clinical-laboratory parameters， high-throughput omics， and molecular biological mechanisms， and proposes the important clinical need for further unifying the definition of Pre-ACLF.
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Key words:
- Acute-On-Chronic Liver Failure /
- End Stage Liver Disease /
- Early Diagnosis
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表 1 Pre-ACLF的近年部分研究结果
Table 1. Partial research findings on pre-acute-on-chronic liver failure in recent years
研究类型 基础肝病 研究中Pre-ACLF的定义 关键指标 结论 前瞻性
队列［9］HBV相关急性失
代偿期肝硬化入院前表现为急性失代偿，且
28 d内依据EASL-CLIF-C标准
诊断为ACLF的患者肝内诱因：HBV再激活的乙型
肝炎复发、高HBV DNA负荷
的自发性乙型肝炎复发、HBV
合并感染；肝外诱因：细菌感
染；疾病严重程度参数：TBil、
INR；全身性炎症参数NLR可有效区分高风险和低风险
患者前瞻性
队列［16］急性失代偿期
肝硬化入院前表现为急性失代偿，且
90 d内依据CANONIC研究标
准诊断为ACLF的患者WBC、CRP Pre-ACLF患者的WBC和
CRP水平显著高于未发展为
ACLF的患者横断面
研究［17］慢性肝病急性加重；极度疲劳
伴有严重消化症状，如明显
厌食、腹部胀大、恶心和呕吐；
黄疸在短时间内逐渐恶化，
5 mg/dL<TBil≤10 mg/dL，或每日
升高≥1 mg/dL；1.28≤INR<1.50
或40%<PTA≤60%血清自毒素 血清自毒素水平在Pre-ACLF
患者中升高，并显著高于未
进展为ACLF的患者回顾性
队列［24］具有慢性肝病 血清TBil≥51 μmol/L，40%<
PTA≤70%，既往肝病急性恶化
但未符合2014版APASL中
ACLF诊断标准的患者TBil、MELD评分、PTA和
Child-Pugh评分TBil、MELD评分、PTA及
Child-Pugh评分的最大变化
率可用于早期预测ACLF
进展前瞻性
队列［25］HBV相关慢性
肝病入院时未符合COSSH-ACLF诊
断标准，且在入院后7 d进展为
符合ACLF诊断标准的患者ALT、TBil、INR和FER 新建预后评分能有效预测
HBV相关慢性肝病急性恶化
患者的短期ACLF发病，并区
分高风险和低风险人群（≥
6.3/<6.3）前瞻性
队列［26］急性失代偿期
肝硬化PREDICT中定义的Pre-ACLF
标准入院时是否肝衰竭、TBil、INR
和MELD评分预测因子7 d变化轨迹可显
著预测ACLF进展前瞻性
队列［27］急性失代偿期
肝硬化PREDICT中定义的Pre-ACLF
标准肝功能损害的严重程度、
全身炎症程度CRP水平、CLIF-C AD评分和
Child-Pugh分级联合预测模
型能有效识别急性失代偿期
肝硬化患者的ACLF发展
风险回顾性
队列［28］CHB 入院前两周内表现为急性失代
偿，且28 d内依据COSSH-
ACLF诊断标准进展为ACLF
的患者C3 低C3水平提示失代偿期肝
硬化患者ACLF的风险升高前瞻性
队列［29］急性失代偿期
肝硬化PREDICT中定义的Pre-ACLF
标准28个免疫细胞相关基因 构建慢性肝衰竭-系统性炎
症基因评分用于评估系统性
炎症强度，并可动态监测炎
症反应进程前瞻性
队列［30］HBV相关慢性肝
病急性加重入院前两周内表现为急性失代
偿，且28 d内依据COSSH-
ACLF标准进展为ACLF的
患者哌啶-2-甲酸、γ-CEHC 代谢物靶向检测方法结合
TBil、INR及肝硬化状态用于
建立Pre-ACLF诊断模型注：HBV，乙型肝炎病毒；EASL，欧洲肝病学会；CLIF-C，慢性肝病联盟；ACLF，慢加急性肝衰竭；TBil，总胆红素；INR，国际标准化比值；NLR，中性粒细胞与淋巴细胞比率；CANONIC，慢性肝衰竭联盟肝硬化慢加急性肝衰竭；WBC，白细胞计数；CRP，C-反应蛋白；Pre-ACLF，慢加急性肝衰竭前期；PTA，凝血酶原活动度；CHB，慢性乙型肝炎；COSSH，中国重型乙型肝炎研究组；C3，血清补体成分3；APASL，亚太肝病学会；MELD，终末期肝病模型；ALT，丙氨酸氨基转移酶；FER，铁蛋白；PREDICT，慢加急性肝衰竭研究；AD，急性失代偿；γ-CEHC，γ-生育酚代谢物。
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