环境与原发性胆汁性肝硬化

Environmental factors and primary biliary cirrhosis

在自身免疫性疾病的发生、发展过程中，免疫与遗传因素发挥着重要作用，原发性胆汁性肝硬化（PBC）也不例外。PBC是以肝内小胆管损伤为特征的自身免疫介导的胆汁淤积性肝病，多伴有线粒体抗体出现。在目前已知的诸多发病危险因素中，基因易感性仍占主导地位，但这无法解释PBC不同的地理分布及同卵双胞胎的不完全一致问题，而这些问题都反映了PBC与特定环境因素存在关联。但是，PBC与环境因素之间清晰合理的关系仍未被彻底阐明。对PBC的环境危险诱因的理解仅限于大量与其发病相关因素的怀疑，如外源性物质、亲电子药物、感染以及其他物理、化学、生物因素等。尽管导致自身免疫耐受打破的因素仍不清楚，但相关地理流行病学的研究可以帮助我们更好地理解环境的影响，这也是改善包括PBC在内的自身免疫性疾病防治和管理的关键。

The complex interplay between immune factors and genetic susceptibility plays an essential role in autoimmune diseases. This is especially true for primary biliary cirrhosis （PBC）. PBC is an autoimmune cholestatic liver disease characterized by the destruction of the small intrahepatic bile ducts and the presence of high-titer antimitochondrial antibodies （AMA）. Among the currently known risk factors, genetic predisposition remains to be the dominant one. However, it is insufficient to explain the different geographic distributions of PBC and the incomplete concordance in identical twins. This suggests an association between specific environmental factors and the development of PBC. Nevertheless, a clear and rational association of environmental factors with primary biliary cirrhosis has not yet been fully elucidated. Our current understanding of the environmental triggers of PBC is limited to numerous suspected factors involved in its development, such as xenobiotics, electrophilic drugs, infection, and other physical, chemical, and even biological factors. Although the factors leading to the breakdown of immune tolerance in PBC are still largely unknown, related geoepidemiological studies may help us better understand the impact of the environment. In addition, a better understanding of the interplay between environmental factors and PBC is the critical step toward improving our management and control of PBC and autoimmunity in general.