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Guideline for diagnosis and treatment of liver failure （2024 version）
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摘要: 肝衰竭是临床常见的严重肝病症候群，病死率极高。多年来，各国学者对肝衰竭的定义、病因、分类、分型、诊断、治疗和预后等问题不断进行探索。根据国内外最新研究成果，中华医学会感染病学分会肝衰竭与人工肝学组和中华医学会肝病学分会重型肝病与人工肝学组在我国《肝衰竭诊治指南（2018年版）》的基础上对指南进行了全面更新，以指导和规范肝衰竭的临床诊疗。Abstract: Liver failure is a severe clinical syndrome of liver disease with an extremely high mortality rate. Over the years， scholars worldwide have continuously investigated various aspects of liver failure， including its definition， etiology， classification， types， diagnosis and treatment， and prognostic assessment. Based on the latest advances in research， Liver Failure and Artificial Liver Group， Chinese Society of Infectious Diseases， Chinese Medical Association along with Severe Liver Disease and Artificial Liver Group， Chinese Society of Hepatology， Chinese Medical Association have conducted a comprehensive update on the Guidelines for Diagnosis and Treatment of Liver Failure （2018 version）. This update aims to offer standardized protocols and evidence-based recommendations to guide the management of liver failure in clinical settings.
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Key words:
- Liver Failure /
- Liver， Artificial /
- Diagnosis /
- Treatment /
- Guideline
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表 1 英国牛津大学循证医学中心证据分级（2011年版）
Table 1. Oxford centre for evidence-based medicine levels of evidence （2011）
证据级别 描述 1 基于随机对照试验的系统评价、全或无研究、效应量大的观察性研究 2 单个随机对照试验、效应量大的观察性研究 3 非随机对照的队列研究，随访研究 4 病例系列、病例对照研究、回顾性对照研究 5 专家意见（基于机制的推理） 
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表 2 GRADE推荐标准
Table 2. GRADE recommendation system
推荐级别 描述 A 强烈推荐：明确显示干预措施利大于弊或弊大于利 B 较弱的推荐：利弊不确定或无论质量高低的证据均显示利弊相当
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表 3 肝衰竭的常见病因
Table 3. Common causes of liver failure
病因 常见分类 肝炎病毒 甲型、乙型、丙型、丁型和戊型肝炎病毒（HAV、HBV、HCV、HDV和HEV） 其他病毒 巨细胞病毒（CMV）、EB病毒（EBV）、新型布尼亚病毒、黄热病毒、裂谷热病毒等 药物 对乙酰氨基酚、抗结核药物、抗肿瘤药物、部分中草药、抗风湿病药物、抗代谢药物、膳食补充剂等 肝毒性物质 酒精、毒蕈、植物、有毒的化学物质等 细菌及寄生虫等 严重或持续感染（如脓毒症、血吸虫病等） 遗传代谢 肝豆状核变性、遗传性糖代谢障碍等 免疫相关 自身免疫性肝病、肿瘤免疫治疗、乙型肝炎不规范抗病毒治疗等 肝脏其他疾病 肝脏肿瘤、肝脏手术、妊娠急性脂肪肝、肝移植术后、肝脏血管疾病（如布加综合征）等 胆道疾病 先天性胆道闭锁、胆汁淤积性肝病等 循环衰竭 缺血缺氧、休克、充血性心力衰竭等 其他 创伤、热射病等 原因不明 - 注：-，无相关数据。
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表 4 肝衰竭的分类
Table 4. Classification of liver failure
分类 定义 急性肝衰竭 急性起病，无基础肝病史，4周以内出现以Ⅱ级及以上肝性脑病为特征的肝衰竭 亚急性肝衰竭 起病较急，无基础肝病史，4～24周出现肝衰竭的临床表现 慢加急性（亚急性）肝衰竭 在慢性肝病基础上（有无肝硬化），各种诱因导致短期内出现急性肝功能恶化，以肝脏和/或肝外器官衰竭和短期高病死率（28 d病死率≥15%）为主要特征的复杂临床综合征 慢性肝衰竭 在肝硬化基础上，缓慢出现肝功能进行性减退导致的以反复腹水和/或肝性脑病等为主要表现的慢性肝功能失代偿
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表 5 慢加急性肝衰竭（ACLF）诊断标准
Table 5. Diagnostic criteria for acute-on-chronic liver failure （ACLF）
项目 COSSH-ACLF［11］ EASL-ACLF［9］ NACSELD-ACLF［10］ APASL专家共识［8］ 世界胃肠病学组织［17］ 临床研究类型 多中心、前瞻性、观察性队列研究 多中心、前瞻性、观察性队列研究 多中心、前瞻性数据库分析 专家共识 专家共识 主要病因 HBV 酒精、HCV HCV、酒精 HBV、酒精 - 发病诱因 肝内（HBV再激活）、肝外（细菌感染）或二者兼有 肝内（酒精性肝炎），肝外（感染、静脉曲张出血），或二者兼有 肝内型、肝外型，或二者兼有 肝内型 - 研究人群 乙型肝炎相关慢性肝病急性失代偿（不论有无肝硬化） 肝硬化急性失代偿 肝硬化急性失代偿 慢性肝病急性失代偿（有失代偿史除外） - ACLF定义 在慢性肝病（无论肝硬化与否）基础上出现的急性肝功能恶化，伴随肝脏和/或肝外器官衰竭（肝、肾、脑、凝血、呼吸和循环）以及短期高病死率（28 d病死率≥15%）的一组复杂临床综合征 肝硬化急性失代偿患者出现多器官功能衰竭（肝、肾、脑、凝血、呼吸和循环），伴随短期高病死率（28 d病死率≥15%）的一组复杂临床综合征 合并感染的肝硬化患者出现2个及以上肝外器官衰竭（肾、脑、呼吸和循环）合并短期（30 d）高病死率 在既往已知或未知的慢性肝病基础上出现急性肝损伤（总胆红素≥5 mg/dL和INR≥1.5）伴有4周内出现腹水或肝性脑病，并有28 d高病死率 慢性肝病患者无论先前是否诊断为肝硬化，存在诱因引起急性肝功能失代偿导致的肝功能衰竭（黄疸和INR延长）和1个或多个肝外器官衰竭，28 d和90 d病死率增加。将ACLF分为3型，A型：在慢性非肝硬化肝病基础上发生；B型：在代偿期肝硬化基础上发生；C型：在既往发生失代偿的肝硬化基础上发生 ACLF分级 ACLF-1级：肝衰竭（总胆红素≥12 mg/dL）合并1.5≤INR<2.5，或合并肾功能障碍（肌酐1.5～1.9 mg/dL），或合并Ⅰ～Ⅱ级肝性脑病；
ACLF-2级：2个器官衰竭；
ACLF-3级：≥3个器官衰竭
ACLF-1级：1个器官衰竭，包括（1）肾衰竭；（2）肝脏、凝血、循环或呼吸衰竭之一合并或肾功能障碍（肌酐1.5～1.9 mg/dL）或1～2级肝性脑病；（3）脑衰竭合并肾功能障碍（肌酐1.5～1.9 mg/dL）；
ACLF-2级：2个器官衰竭；
ACLF-3级：≥3个器官衰竭
- 1级：AARC评分5～7分；
2级：AARC评分8～10分；
3级：AARC评分11～15分
- 器官衰竭定义 肝脏：总胆红素≥12 mg/dL；肾脏：肌酐≥2 mg/dL或使用连续性肾脏替代治疗；
凝血功能：INR≥2.5；
脑：West Haven分级3～4级肝性脑病或因肝性脑病使用机械通气；
循环系统：血管活性药物的使用；
呼吸系统：PaO2/FiO2≤200或SpO2/FiO2≤214或非肝性脑病使用机械通气
同COSSH标准下器官衰竭定义 肾脏：使用透析或其他形式的连续性肾脏替代治疗；
脑：West Haven分级3～4级；
循环系统：尽管有液体复苏和足够的心输出量，但平均动脉压<60 mmHg或收缩压较基础值降低40 mmHg；
呼吸系统：使用机械通气
肝脏：总胆红素≥5 mg/dL；
脑：临床肝性脑病
- 等级分布 1级：61%；
2级：33%；
3级：6%
1级：49%；
2级：35%；
3级：16%
2个器官衰竭：43%；
3个器官衰竭：41%；
4个器官衰竭：16%
- - 短期病死率 28 d
1级：23%；
2级：61%；
3级：93%
28 d
1级：22%；
2级：32%；
3级：77%
30 d
2个器官衰竭：49%；
3个器官衰竭：64%；
4个器官衰竭：77%
28 d
1级：13%；
2级：45%；
3级：86%
- 注：-，无相关数据；COSSH，中国重型乙型病毒性肝炎研究小组；EASL，欧洲肝病学会；NACSELD，北美终末期肝病研究联盟；APASL，亚太肝病学会；HBV，乙型肝炎病毒；HCV，丙型肝炎病毒；INR，国际标准化比值；1 mmHg=0.133 kPa。
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表 6 慢加急性肝衰竭（ACLF）预警预后评分
Table 6. Early warning and prognostic scoring for acute-on-chronic liver failure （ACLF）
评分模型 应用人群 评价指标 评分公式 应用 预后评分模型 COSSH-ACLF Ⅱs［34］ 慢性肝病急性失代偿（不论有无肝硬化） INR、HE等级、中性粒细胞、TBil、血尿素、年龄 =1.649×ln（INR）+0.457×HE评分+0.425×ln（中性粒细胞）+0.396×ln（TBil）+ 0.576×ln（血尿素）+ 0.033×年龄 患者病死率的个体评估；
危险分层，28/90 d病死率：
<7分（低风险），8.2%/18.7%；
7～<8.4分（中风险），49.7%/65.8%；
≥8.4分（高风险），76.3%/87.7%
COSSH-ACLFs［11］ 慢性肝病急性失代偿（不论有无肝硬化） HBV-SOFA评分（包括肾、脑、循环和呼吸功能的判断）、INR、TBil、年龄 =0.741×INR+0.523×HBV-SOFA+0.026×年龄+ 0.003×TBil（μmol/L） - CLIF-C ACLFs［33］ 肝硬化急性失代偿性 CLIF-OF评分（包括肝、凝血、肾、脑、循环和呼吸功能的判断）、年龄、白细胞 =10×［0.33×CLIF OFs+0.04×年龄+0.63×ln（白细胞）－2］ 患者病死率的个体评估 APASL-AARCs［35］ 慢性肝病急性恶化 TBil、Cre、INR、HE等级、血乳酸 - 危险分层，28 d病死率：
5～7分/ACLF-1级：13%
8～10分/ACLF-2级：45%
11～15分/ACLF-3级：86%
NACSELD-ACLFs［36］ 肝硬化急性失代偿 HE等级、肾脏替代治疗、机械通气、平均动脉压 - ≥2个器官衰竭的30 d病死率：41% 预警评分模型 COSSH-onset-ACLFs［37］ 慢性肝病急性失代偿（不论有无肝硬化） ALT、TBil、INR、铁蛋白 =0.101×ln（ALT）+0.819×ln（TBil）+2.820×ln（INR）+ 0.016×ln（铁蛋白） 预测肝衰竭发生率；
危险分层，7/14/28 d发生率：
<6.3分（低风险），2.5%/3.2%/3.7%；
≥6.3分（高风险），42.6%/49.2%/50.0%
注：-，无相关数据；COSSH，中国重型乙型病毒性肝炎研究小组；APASL，亚太肝病学会；INR，国际标准化比值；HE，肝性脑病；HBV，乙型肝炎病毒；ALT，丙氨酸转氨酶；Cre，血肌酐；TBil，总胆红素。
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