《生命科学》 2026, 38(3): 463-481
慢加急性肝衰竭治疗新突破：从传统疗法到新兴靶向治疗
摘 要：
慢加急性肝功能衰竭（acute-on-chronic liver failure，ACLF）是在慢性肝病基础上由急性损伤因素诱发的肝功能急剧恶化临床综合征，其核心特征为短期高死亡率和多器官功能衰竭，给社会和家庭带来沉重负担。目前ACLF缺乏特异性治疗手段，传统治疗以内科支持治疗、非生物型人工肝以及肝移植为主，存在疗效有限、供体短缺等多种局限。随着对ACLF病理生理机制研究的深入，系统性炎症、免疫功能障碍及多器官损伤等分子机制逐渐明确，为新兴靶向治疗提供了科学依据。本文系统性阐述了ACLF的定义标准、病理生理机制以及传统治疗（内科支持治疗、非生物型人工肝、肝移植）的方法和局限性。文章重点探讨了干细胞治疗、高级人工支持系统、免疫调节、基因治疗、肠道微生态干预及中药治疗等新兴疗法的作用机制、治疗潜力及研究进展。ACLF的治疗方案正在从传统对症支持治疗向精准靶向治疗转变，随着多组学研究的不断深入，个体化精准治疗将有望成为提高ACLF临床治愈率的关键方向。
通讯作者：王瑞松 , Email:ruisong.wang@huas.edu.cn
Abstract:
Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by acute decompensation of chronic liver disease, multisystem organ failure, and high short-term mortality. Current standard-of-care, including comprehensive medical management and non-biological artificial liver support, primarily focuses on symptomatic relief and bridging to transplantation. However, these traditional approaches are limited by donor shortages, high costs, and an inability to reverse the core pathological deterioration. This review aims to systematically analyze the pathophysiological mechanisms of ACLF and provide an in-depth evaluation of emerging targeted therapies that signal a paradigm shift from passive support to active functional regeneration. The article first delineates the evolving definitions and diagnostic criteria of ACLF, identifying systemic inflammation, immune paresis, and mitochondrial dysfunction as the central drivers of disease progression. Against this background, the review categorizes and critically assesses a wide array of novel therapeutic strategies. Key interventions discussed include: (1) stem cell therapies: the efficacy of mesenchymal stem cells (MSCs) and gene-modified MSCs in modulating immunity and promoting tissue repair; (2) advanced support systems: the evolution from mechanical filtration to bioartificial livers (BAL) and 3D-printed hepatic organoids; (3) immunomodulation and molecular targeting: novel biologic agents and targets such as recombinant alkaline phosphatase (RecAP), gasdermin D (GSDMD)-mediated pyroptosis inhibitors, mitochondrial fusion protein 2 (Mfn2), and thrombospondin-1 (THBS1); and (4) microbiome interventions: the role of fecal microbiota transplantation (FMT) in restoring the gut-liver axis. Additionally, the potential of traditional Chinese medicine (TCM) and network pharmacology is explored.While emerging therapies demonstrate significant potential to inhibit the ″cytokine storm″, restore metabolic homeostasis, and facilitate liver regeneration, challenges regarding safety protocols, standardization, and clinical translation remain. The authors propose that the future of ACLF treatment lies in precision medicine, facilitated by single-cell multi-omics analysis and artificial intelligence, to stratify patients for individualized regimens. Ultimately, the therapeutic landscape is transitioning from ″organ replacement″ to ″functional regeneration″ and ″immune restoration", offering a promising roadmap for achieving clinical cures and improving long-term survival in ACLF patients.
Communication Author：WANG Rui-Song , Email:ruisong.wang@huas.edu.cn
SciCloud投稿系统