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Hierarchical diagnosis and treatment pathway and multidisciplinary collaborative intelligent holistic management protocol for metabolic dysfunction-associated fatty liver disease within the Hepatology Specialty Alliance framework： An integrated traditional Chinese and Western medicine approach
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摘要: 代谢相关脂肪性肝病（MAFLD）已成为我国慢性肝病的主要病因，其与心血管疾病、2型糖尿病等多种代谢紊乱密切关联，共同构成一种复杂的全身性疾病。当前临床实践中，筛查与风险分层工具的应用缺乏标准化，跨学科协作机制亦不完善，导致MAFLD全程管理效率受限，患者预后差异显著。为应对上述挑战，本文基于肝病专科联盟体系，构建了一套科学、系统且具有可操作性的MAFLD分级诊疗与全程管理临床路径。该路径的核心内容包括：确立基于影像学与代谢异常的双维度诊断标准；明确以无创纤维化-4指数作为肝病专科联盟内初始风险分层的关键节点，联合肝脏硬度测定实现精准分流；系统制定肝病科与内分泌科、心内科、营养科等多学科间的双向转诊指征及协作流程；在强化生活方式干预基础上，整合循证药物治疗与中医辅助干预策略。此外，本文前瞻性提出以数据驱动、智能预警与全病程随访为特征的智慧化管理平台框架。本临床路径旨在为肝病专科联盟体系下各级医疗机构提供标准化MAFLD管理工具，推动从“单一肝病诊疗”向“多系统共病一体化管理”模式转变，以期最终降低肝病及心血管相关终点事件风险，改善患者长期预后。Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the leading cause of chronic liver disease in China， and it is closely intertwined with various metabolic disorders such as cardiovascular diseases and type 2 diabetes， collectively constituting a complex systemic condition. Current clinical practice still faces the challenges including non-standardized application of screening and risk stratification tools， and a lack of multidisciplinary collaboration mechanisms， which lead to inefficient holistic management of MAFLD and significant variability in prognosis. To address these challenges， this study developed a scientific， systematic， and operable clinical pathway for hierarchical diagnosis and treatment and holistic management of MAFLD based on the Hepatology Specialty Alliance framework. The core components of this pathway include the following aspects： establishing dual-dimensional diagnostic criteria based on imaging and metabolic abnormalities； defining the non-invasive fibrosis-4 index as the key node for initial risk stratification within the alliance， combined with liver stiffness measurement for precise patient triage； systematically formulating bidirectional referral indications and collaborative workflows among hepatology， endocrinology， cardiology， and nutrition departments； integrating evidence-based pharmacological therapy and traditional Chinese medicine adjuvant strategies on the basis of intensified lifestyle intervention. Furthermore， this study prospectively proposes a framework for an intelligent management platform characterized by data-driven decision-making， smart early warning， and whole-course follow-up. This clinical pathway aims to provide standardized MAFLD management tools for healthcare institutions at all levels within the Hepatology Specialty Alliance system， and it seeks to promote a shift from the model of “diagnosis and treatment of a single liver disease” to a paradigm of “integrated management of multi-system comorbidities”， in order to reduce the risk of liver diseases and cardiovascular endpoint events and improve the long-term prognosis of patients.
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注： BMI，体重指数；ALT，丙氨酸氨基转移酶；AST，天冬氨酸氨基转移酶；ALP，碱性磷酸酶；GGT，γ-谷氨酰转移酶；AI，人工智能；FIB-4指数，纤维化-4指数；LSM，肝脏硬度测定；MAFLD，代谢相关脂肪性肝病；MASH，代谢相关脂肪性肝炎；PLT，血小板计数；HOMA-IR，胰岛素抵抗指数；ASCVD，动脉粥样硬化性心血管疾病。
图 1 肝病专科联盟体系下MAFLD中西医结合分级诊疗与多学科协作全程管理路径
Figure 1. An integrated management pathway for MAFLD within a hepatology specialist alliance： Combining traditional Chinese and western medicine through multidisciplinary team
注： 1）适用于65岁及以上人群的FIB-4指数评估阈值（年龄≥65岁的患者，FIB-4指数分界值为2.0）；2）包括生活方式干预、合并症的治疗、减重手术等；A或B策略的选择基于对患者病史、临床状况的综合评估，并兼顾当地医疗资源的可及性。MAFLD，代谢相关脂肪性肝病；FIB-4指数，纤维化-4指数。
图 3 肝病科与内分泌科MAFLD患者双向转诊流程
Figure 3. Bidirectional referral pathway for MAFLD patients between hepatology and endocrinology
注： ALT，丙氨酸氨基转移酶；AST，天冬氨酸氨基转移酶；ULN，正常值上限；CK，肌酸激酶；TG，甘油三酯；ASCVD，动脉粥样硬化性心血管疾病；ACS，急性冠脉综合征；LDL-C，低密度脂蛋白胆固醇；CKD，慢性肾脏病；TC，总胆固醇；HDL-C，高密度脂蛋白胆固醇；BMI，体重指数。
图 4 血液净化科血浆分离单采技术去脂治疗转诊及评估流程
Figure 4. Referral and assessment pathway for lipid apheresis in the blood purification service
注： MASH，代谢相关脂肪性肝炎；MAFLD，代谢相关脂肪性肝病。
图 5 MAFLD患者多学科协作管理架构图
Figure 5. Multidisciplinary team management framework for patients with MAFLD
注： MAFLD，代谢相关脂肪性肝病；FIB-4指数，纤维化-4指数；LSM，肝脏硬度测定；GLP-1，胰高血糖素样肽-1；SGLT2，钠-葡萄糖协同转运蛋白2；MASH，代谢相关脂肪性肝炎；GIP，葡萄糖依赖性促胰岛素多肽。
图 6 糖尿病合并MAFLD患者的共管策略
Figure 6. Coordinated co-management strategy for patients with concomitant diabetes and MAFLD
注： MAFLD，代谢相关脂肪性肝病。
图 7 MAFLD患者全病程人工智能管理流程
Figure 7. Artificial intelligence-integrated clinical management protocol for MAFLD throughout the lifecourse
诊断步骤 内容 步骤一 影像学诊断脂肪肝和/或肝脏组织病理检查≥5%肝细胞大泡性脂肪变性 步骤二 （1）排除可能导致脂肪肝的其他原因及排除过量饮酒（每周乙醇摄入量男性≥210 g，女性≥140 g）；若不能排除，患者
合并肥胖和/或2型糖尿病、代谢综合征则为MAFLD合并酒精性肝病（2）排除继发性脂肪性肝病（如存在基因3型丙型肝炎病毒感染、药物性脂肪肝、肝豆状核变性和营养不良等可导致
脂肪肝的疾病）；若不能排除，患者合并肥胖和/或2型糖尿病、代谢综合征则为MAFLD合并继发性脂肪肝疾病步骤三 至少存在一项代谢心血管疾病危险因素： （1）BMI≥24.0 kg/m2，或者腰围≥90 cm（男性）和 85 cm（女性），或者体脂肪含量与体脂百分比超标 （2）动脉血压≥130/85 mmHg，或者在接受降血压药物治疗 （3）空腹血糖≥6.1 mmol/L，或者糖负荷后2 h血糖≥7.8 mmol/L或 HbA1c≥5.7%，或者2型糖尿病史，或者HOMA-IR≥2.5 （4）空腹血清甘油三酯≥1.70 mmol/L，或者正在接受降血脂药物治疗 （5）血清高密度脂蛋白胆固醇≤1.0 mmol/L（男性）和1.3 mmol/L（女性），或者正在接受降血脂药物治疗 注：MAFLD，代谢相关脂肪性肝病；BMI，体重指数；HbA1c，糖化血红蛋白；HOMA-IR，胰岛素抵抗指数。
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表 2 肝脂肪变性的无创评估
Table 2. Non-invasive assessment of hepatic steatosis
诊断技术 技术名称 核心特点 局限性 超声 超声显像 最为常用，可诊断弥漫性和不均
质性脂肪肝敏感性低于CAP/UAP技术；仅能定性或
半定量评估，精度不足瞬时弹性成像相关技术 CAP（FibroScan®） 通过超声波衰减定量评估脂肪含
量。敏感性高于超声显像，可连
续监测脂肪变化肥胖患者腹壁厚（>25 mm）、中-大量腹水
等患者不适于该检查；
重度肥胖、非空腹状态、血清 ALT显著升
高，以及肝脏淤血、淤胆及重度肝脂肪变
性可影响检测结果UAP（FibroTouch®） 原理与CAP相近，数值参考范围
相近磁共振技术 磁共振质子密度脂肪分数 客观准确评估全肝脂肪含量，为
临床试验常用评估标准检测成本高，设备普及率低，检查耗时
较长注：CAP，受控衰减参数；UAP，超声衰减参数；ALT，丙氨酸氨基转移酶。
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