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酒精性肝病相关慢加急性肝衰竭：机制、动态评估与精准管理
DOI: 10.12449/JCH260803
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：艾娜负责拟定写作思路，起草并撰写论文；崔怀宁、方晓慧和柳涛负责收集相关资料并对论文进行修改；高沿航负责设计论文框架，指导撰写并修改文章及最终定稿。
Alcohol-related liver disease-associated acute-on-chronic liver failure: Mechanisms, dynamic assessment, and precise management
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摘要: 慢加急性肝衰竭（ACLF）是慢性肝病急性恶化期的高病死率综合征，以系统性炎症驱动的多器官功能障碍为核心特征。酒精性肝病相关慢加急性肝衰竭（ALD-ACLF）因肠道微生态失衡、内毒素易位及炎症反应放大更为突出，常伴随较高的继发感染风险和肝外器官受累，具有明显的病因学与临床特异性。本综述系统梳理ALD-ACLF的概念边界、病理生理机制、动态预警与预后评估进展，重点评述风险分层及临床管理决策要点，并探讨代谢功能障碍合并酒精相关肝病双重打击表型对ALD-ACLF风险分层的潜在影响。提示临床应进一步强化病因导向的早期识别、动态分层、诱因控制和干预前移，以期为该类患者的精准评估及个体化干预提供参考。Abstract: Acute-on-chronic liver failure （ACLF） is a high-mortality syndrome that develops during the acute deterioration of chronic liver disease and is characterized by multiple organ dysfunction driven by systemic inflammation. Due to gut microbiota dysbiosis， endotoxin translocation， and amplified inflammatory responses， alcohol-related liver disease-associated ACLF （ALD-ACLF） is more pronounced and is often accompanied by a high risk of secondary infection and extrahepatic organ involvement， thereby exhibiting distinct etiological and clinical characteristics. This article systematically reviews the advances in the definitional boundaries， pathophysiological mechanisms， dynamic early warning， and prognostic assessment of ALD-ACLF， elaborates on risk stratification and key issues in clinical management， and discusses the potential impact of the dual-hit phenotype of metabolic dysfunction and alcohol-related liver disease on risk stratification in ALD-ACLF. This article also highlights the need to further strengthen etiology-oriented early identification， dynamic stratification， control of predisposing factors， and earlier intervention， in order to provide a reference for the precise assessment and individualized intervention of these patients.
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注： ALD-ACLF，酒精性肝病相关慢加急性肝衰竭；LPS，脂多糖；PAMP，病原体相关分子模式；TLR4，Toll样受体4；MyD88，髓样分化因子88；NF-κB，核因子κB；IRF3，干扰素调节因子3；p38/ERK MAPK通路，p38/细胞外信号调节激酶丝裂原活化蛋白激酶通路；TNF-α，肿瘤坏死因子α；IL-6，白细胞介素6；IL-1β，白细胞介素1β；IL-8，白细胞介素8；CCL2，CC亚族趋化因子配体2；ROS，活性氧；DAMP，损伤相关分子模式；SIRS，全身炎症反应综合征；CARS，代偿性抗炎反应综合征；HLA-DR，人类白细胞抗原DR；MERTK，Mer受体酪氨酸激酶；CD163，白细胞分化抗原163；PD-L1，程序性死亡受体配体1。
图 1 ALD-ACLF病理与病理生理学机制
Figure 1. Pathological and pathophysiological mechanisms of ALD-ACLF
表 1 SAH、ALD相关急性失代偿与ALD-ACLF临床特征比较
Table 1. Comparison of clinical characteristics among SAH， ALD-related acute decompensation， and ALD-ACLF
项目 SAH ALD相关急性失代偿 ALD-ACLF 疾病特点 ALD最严重炎症表型，重症者常突发黄
疸和肝衰竭失代偿期并发症加重，但未进
入ACLF在SAH/ALD基础上由感染和/或系统性
炎症触发的多器官衰竭综合征发病机制 酒精毒性、氧化应激、肠-肝轴失衡及肝
内炎症共同驱动以长期肝纤维化/肝硬化、门静
脉高压及肝合成功能减退为主慢性肝损伤基础上叠加感染和/或系统
性炎症，导致免疫失衡及器官衰竭病理特点 脂肪变、胆汁淤积、肝细胞周围纤维化、
中性粒细胞浸润、肝细胞气球样变及马
洛里小体以肝硬化结节形成、纤维间隔
及门静脉高压相关结构改变
为主ALD病变基础上叠加系统性炎症和器
官衰竭表型临床表现 突发黄疸、肝衰竭，可伴凝血障碍、营养
不良和感染风险升高以腹水、肝性脑病及静脉曲张
出血等失代偿表现为主在黄疸和肝功能恶化基础上出现多系
统受累，常伴感染及器官功能障碍器官衰竭 以肝衰竭为主，重症时可进展为ACLF 一般无明确多器官衰竭 可导致多器官衰竭 短期预后 差 差 最差 治疗策略 戒酒、营养支持、纠正维生素缺乏，重症者
可使用糖皮质激素，4 d或7 d以Lille评分
评估反应，无应答者考虑早期肝移植按照失代偿期肝硬化处理，控
制并发症，并强化戒酒管理在上述基础上强调器官支持、积极控制
感染或炎症诱因，并尽早评估肝移植注：ALD，酒精性肝病；SAH，重症酒精性肝炎；ALD-ACLF，酒精性肝病相关慢加急性肝衰竭；ACLF，慢加急性肝衰竭；Lille评分，皮质类固醇治疗反应动态评估指标。
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表 2 ALD-ACLF预后评分体系对比
Table 2. Comparison of prognostic scoring systems for ALD-ACLF
模型名称 主要参数 适用人群 核心优势 主要局限性 近3年进展 MELD 3.0 胆红素、INR、
肌酐、血钠、白
蛋白和性别终末期肝病、肝移植
等待患者计算简便，应用广泛，为
肝移植分配基础对系统性炎症反
应及肝外器官衰
竭反映不足在酒精相关肝炎和酒精性肝
硬化急性恶化队列中显示出
较好的短期死亡预测效能CLIF-C
ACLF基于6个器官
系统衰竭评
估，纳入年龄、
白细胞计数EASL定义下ACLF
患者可同时反映多器官功能
衰竭和炎症负荷，适用于
28 d/90 d死亡预测、ICU
分层及移植决策计算相对复杂，
在极重症ICU患
者中的预测效能
有限近年ICU验证研究进一步支
持其临床分层价值；CLIF-C
ACLF>70分提示极高短期死
亡风险AARC 胆红素、INR、
肌酐、乳酸及
肝性脑病APASL定义下ACLF
患者具有肝衰竭起始表型及
动态再评估价值，适用于
住院早期连续风险分层对呼吸、循环衰
竭表征较弱；跨
地区外推性有限京都共识进一步强化AARC
动态评估在治疗反应判断及
短期预后分层中的应用价值注：ALD-ACLF，酒精性肝病相关慢加急性肝衰竭；MELD，终末期肝病模型；CLIF-C ACLF，慢性肝衰竭联盟慢加急性肝衰竭评分；AARC，亚太肝病学会慢加急性肝衰竭研究联盟评分；INR，国际标准化比值；EASL，欧洲肝病学会；ACLF，慢加急性肝衰竭；APASL，亚太肝病学会；ICU，重症监护病房。
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表 3 不同病因相关ACLF的临床特征比较
Table 3. Comparison of the clinical characteristics of ACLF associated with different etiologies
项目 ALD-ACLF HBV-ACLF HCV-ACLF AIH-ACLF 常见诱因 持续饮酒或复饮、SAH、细
菌感染HBV再激活、停药、病毒学
反弹后免疫暴发感染、出血或药物打击 免疫暴发、减停免疫抑制
后反跳炎症特点 中性粒细胞主导，高炎症
负荷肝内免疫损伤和肝细胞坏
死突出多与失代偿基础上的继发打击
有关自身免疫攻击介导 器官衰竭 肝外器官衰竭突出 以肝衰竭为主 肝衰竭或多器官功能障碍并见 可迅速进展为重度肝衰竭 治疗重点 戒酒、抗感染、营养支持、
AKI/HRS管理尽早启动抗病毒治疗、肝
支持、移植评估去除诱因、器官支持、活动性
HCV评估抗病毒时机评估糖皮质激素反应，移
植评估预后关键 感染控制、AKI进展、肝外
器官衰竭负荷肝细胞残存功能、胆红素
及INR变化肝功能储备、诱因可逆性、器官
衰竭程度激素反应性、肝衰竭进展
程度及移植时机注：ACLF，慢加急性肝衰竭；ALD，酒精性肝病；HBV，乙型肝炎病毒；HCV，丙型肝炎病毒；AIH，自身免疫性肝炎；SAH，重症酒精性肝炎；AKI，急性肾损伤；HRS，肝肾综合征；INR，国际标准化比值。
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[1] Raya Tonetti F, Eguileor A, Mrdjen M, et al. Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease[J]. Hepatology, 2024, 80( 6): 1342- 1371. DOI: 10.1097/HEP.0000000000000924. [2] Choudhury A, Kulkarni A V, Arora V, et al. Acute-on-chronic liver failure(ACLF): The‘Kyoto consensus’-steps from Asia[J]. Hepatol Int, 2025, 19( 1): 1- 69. DOI: 10.1007/s12072-024-10773-4. [3] European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute-on-chronic liver failure[J]. J Hepatol, 2023, 79( 2): 461- 491. DOI: 10.1016/j.jhep.2023.04.021. [4] Alvarado-Tapias E, Pose E, Gratacós-Ginès J, et al. Alcohol-associated liver disease: Natural history, management and novel targeted therapies[J]. Clin Mol Hepatol, 2025, 31( Suppl): S112- S133. DOI: 10.3350/cmh.2024.0709. [5] Artru F, McPhail M J. Immunopathogenesis of acute on chronic liver failure[J]. Am J Transplant, 2024, 24( 5): 724- 732. DOI: 10.1016/j.ajt.2024.02.001. [6] Guan Y K, Peiffer B, Feng D C, et al. IL-8+ neutrophils drive inexorable inflammation in severe alcohol-associated hepatitis[J]. J Clin Invest, 2024, 134( 9): e178616. DOI: 10.1172/JCI178616. [7] Nedunchezhian S, Shetty A, Bhat G, et al. Role of procalcitonin in identifying systemic inflammatory response syndrome and sepsis in acute-on-chronic liver failure and its impact on survival[J]. BMC Gastroenterol, 2025, 25( 1): 797. DOI: 10.1186/s12876-025-04352-6. [8] Shen H Y, Liangpunsakul S, Iwakiri Y, et al. Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease[J]. Cell Mol Immunol, 2025, 22( 10): 1190- 1204. DOI: 10.1038/s41423-025-01291-w. [9] Jophlin L L, Singal A K, Bataller R, et al. ACG clinical guideline: Alcohol-associated liver disease[J]. Am J Gastroenterol, 2024, 119( 1): 30- 54. DOI: 10.14309/ajg.0000000000002572. [10] Nadim M K, Kellum J A, Forni L, et al. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative(ADQI) and International Club of Ascites(ICA) joint multidisciplinary consensus meeting[J]. J Hepatol, 2024, 81( 1): 163- 183. DOI: 10.1016/j.jhep.2024.03.031. [11] Wan Z H, Wang J J, You S L, et al. Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure[J]. World J Gastroenterol, 2013, 19( 48): 9432- 9438. DOI: 10.3748/wjg.v19.i48.9432. [12] Yoo J J, Park M Y, Kim S G. Acute kidney injury in patients with acute-on-chronic liver failure: Clinical significance and management[J]. Kidney Res Clin Pract, 2023, 42( 3): 286- 297. DOI: 10.23876/j.krcp.22.264. [13] Rafaqat S, Radoman Vujacic I, Behnoush A H, et al. Role of cardiac biomarkers in hepatic disorders: A literature review[J]. Metab Syndr Relat Disord, 2024, 22( 4): 251- 262. DOI: 10.1089/met.2023.0282. [14] Šimić S, Svaguša T, Grgurević I, et al. Markers of cardiac injury in patients with liver cirrhosis[J]. Croat Med J, 2023, 64( 5): 362- 373. DOI: 10.3325/cmj.2023.64.362. [15] Díaz L A, Fuentes-López E, Ayares G, et al. MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis[J]. JHEP Rep, 2023, 5( 8): 100727. DOI: 10.1016/j.jhepr.2023.100727. [16] Nagel M, Westphal R, Hilscher M, et al. Validation of the CLIF-C OF score and CLIF-C ACLF score to predict transplant-free survival in patients with liver cirrhosis and concomitant need for intensive care unit treatment[J]. Medicina(Kaunas), 2023, 59( 5): 866. DOI: 10.3390/medicina59050866. [17] Maiwall R, Pasupuleti S S R, Choudhury A, et al. AARC score determines outcomes in patients with alcohol-associated hepatitis: A multinational study[J]. Hepatol Int, 2023, 17( 3): 662- 675. DOI: 10.1007/s12072-022-10463-z. [18] Zhang Q, Hu J X, Qiu S T, et al. Clinical differences between HBV and alcohol related ACLF in a WGO classification multicenter study[J]. Sci Rep, 2025, 15( 1): 25292. DOI: 10.1038/s41598-025-09620-9. [19] Reiberger T, Lens S, Cabibbo G, et al. EASL position paper on clinical follow-up after HCV cure[J]. J Hepatol, 2024, 81( 2): 326- 344. DOI: 10.1016/j.jhep.2024.04.007. [20] European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis[J]. J Hepatol, 2025, 83( 2): 453- 501. DOI: 10.1016/j.jhep.2025.03.017. [21] Rinella M E, Lazarus J V, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature[J]. J Hepatol, 2023, 79( 6): 1542- 1556. DOI: 10.1016/j.jhep.2023.06.003. [22] Arab J P, Díaz L A, Rehm J, et al. Metabolic dysfunction and alcohol-related liver disease(MetALD): Position statement by an expert panel on alcohol-related liver disease[J]. J Hepatol, 2025, 82( 4): 744- 756. DOI: 10.1016/j.jhep.2024.11.028. [23] Marti-Aguado D, Calleja J L, Vilar-Gomez E, et al. Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease[J]. J Hepatol, 2024, 81( 6): 930- 940. DOI: 10.1016/j.jhep.2024.06.036. [24] He S K, Liu C H, Wang Y, et al. The prognostic value of sarcopenia in acute-on-chronic liver failure: A systematic review and meta-analysis[J]. BMC Gastroenterol, 2025, 25( 1): 300. DOI: 10.1186/s12876-025-03926-8. [25] Ochoa-Allemant P, Hubbard R A, Kaplan D E, et al. Adverse liver outcomes, cardiovascular events, and mortality in steatotic liver disease[J]. JAMA Intern Med, 2025, 185( 8): 986- 995. DOI: 10.1001/jamainternmed.2025.1809. [26] Ochoa-Allemant P, Hubbard R A, Kaplan D E, et al. Cause-specific mortality in patients with steatotic liver disease in the United States[J]. J Hepatol, 2025, 83( 4): 860- 869. DOI: 10.1016/j.jhep.2025.05.013. [27] Hong X, Huang S, Jiang H, et al. Alcohol-related liver disease(ALD): Current perspectives on pathogenesis, therapeutic strategies, and animal models[J]. Front Pharmacol, 2024, 15: 1432480. DOI: 10.3389/fphar.2024.1432480. [28] Singeap A M, Minea H, Petrea O, et al. Real-world utilization of corticosteroids in severe alcoholic hepatitis: Eligibility, response, and outcomes[J]. Medicina(Kaunas), 2024, 60( 2): 311. DOI: 10.3390/medicina60020311. [29] European Association for the Study of the Liver. EASL Clinical Practice Guidelines on liver transplantation[J]. J Hepatol, 2024, 81( 6): 1040- 1086. DOI: 10.1016/j.jhep.2024.07.032. [30] Kimmann M, Trebicka J. Acute-on-chronic liver failure: Current interventional treatment options and future challenges[J]. J Pers Med, 2023, 13( 7): 1052. DOI: 10.3390/jpm13071052. -
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