Department of Propaedeutics of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia.
World J Gastroenterol. 2023 Oct 7;29(37):5292-5304. doi: 10.3748/wjg.v29.i37.5292.
Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO) buffer system "biliary HCO umbrella". The impaired production and entry of HCO from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.
原发性胆汁性胆管炎（PBC）是一种慢性胆汁淤积性进行性肝脏疾病，也是成人最重要的进行性胆管疾病之一。胆管细胞损伤会引发肝内胆汁淤积，在疾病终末期进展为肝硬化。越来越多的数据表明，胆管上皮细胞（BECs，胆管细胞）的损伤最可能与胆汁酸在细胞内的积累有关，胆汁酸具有很强的去污特性，对细胞膜有损伤作用。PBC 中胆汁酸不受控制地摄入 BECs 的机制与胆管腔内 pH 值的变化有关，该变化由碳酸氢盐（HCO）缓冲系统“胆管 HCO 保护伞”控制。BECs 中 HCO 的产生和进入胆管腔受损是由于 X 连锁微小 RNA 506 的表达发生表观遗传改变所致。基于对 PBC 患者胆管细胞损伤的分子机制的不断增加的认识，我们提出了一个假说，解释了疾病无症状阶段的第一个形态学（胆管减少症）、免疫学（抗线粒体自身抗体）和临床（乏力、不适、快速疲劳）体征的发病机制。本综述重点考虑了这些机制。
