原发性胆汁性胆管炎与自身免疫性肝炎重叠综合征：诊断挑战、“灰色地带”的临床识别与治疗进展

PBC-AIH Overlap Syndrome: Diagnostic Challenges, Clinical Recognition of the “Grey Zone” and Treatment Updates

摘要: 原发性胆汁性胆管炎(PBC)与自身免疫性肝炎(AIH)重叠综合征(OS)是一类兼具两者特征的复杂自身免疫性肝病亚型。目前广泛采用的巴黎标准因生化与组织学阈值过高(如要求ALT ≥ 5 × ULN、IgG ≥ 2 × ULN等)，导致逾76%具有重叠特征的患者被归入“灰色地带”——即兼具双重特征但ALT仅达2~4 × ULN、IgG仅达1.2~1.9 × ULN或AMA阳性伴轻度转氨酶异常而无典型胆管炎。对比更为宽松的Zhang标准，巴黎标准极易漏诊，近半数患者处于两标准间的模糊地带。若对该群体仅按单一疾病处理，将显著增加肝硬化和肝衰竭的风险。本文系统回顾PBC-AIH重叠综合征的概念演变与诊断局限，重点剖析“灰色地带”的临床识别特征、个体化治疗策略及未来研究方向，旨在为临床早期精准决策提供循证参考。

Abstract: Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) Overlap Syndrome (OS) is a complex subtype of autoimmune liver disease characterized by the concurrent presentation of both conditions. The currently widely adopted Paris Criteria impose stringent biochemical and histological thresholds (e.g., ALT ≥ 5 × ULN, IgG ≥ 2 × ULN), relegating over 76% of patients with overlapping features into a diagnostic “grey zone”. These patients often exhibit dual characteristics but with only mild-to-moderate abnormalities, such as ALT at 2~4 × ULN, IgG at 1.2~1.9 × ULN, or Antimitochondrial Antibody (AMA) positivity with mild transaminase elevation yet lacking typical cholangitis. Compared to the more lenient Zhang Criteria, the Paris Criteria are highly susceptible to underdiagnosis, leaving nearly half of the patients in an ambiguous space between the two standards. Managing this “grey zone” population as having merely a single disease significantly increases their risk of progression to liver cirrhosis and hepatic failure. This review systematically evaluates the conceptual evolution and diagnostic limitations of PBC-AIH OS, with a specific focus on the clinical identification of the “grey zone”, individualized therapeutic strategies, and future research directions. Ultimately, it aims to provide an evidence-based reference for early, precise clinical decision-making.