Envoi Specialist Pathologists, Kelvin Grove, Australia 4059; Faculty of Medicine, University of Queensland, Herston, Australia 4006.
Hum Pathol. 2020 Feb;96:2-7. doi: 10.1016/j.humpath.2019.10.006. Epub 2019 Dec 23.
Although severe deficiencies of canalicular transporter enzymes due to biallelic mutations are well known as causes of progressive cholestatic liver disease in children, it is increasingly recognized that milder disease may occur if a single, heterozygous gene mutation is present. This mild disease, generally presenting initially in adulthood, may have a variety of clinical and histological appearances. Bland canalicular cholestasis is the prototypic change, but it is now clear that some gene mutations, particularly in ABCB4 (encoding MDR3), can cause other patterns that include early cholesterol calculus formation, bile duct injury and disappearance, ductular reactions mimicking large duct obstruction, and, in rare cases, progressive fibrosis. Because the features can be subtle and not diagnostic in isolation, it is generally the combination of a biliary pattern of injury with a suggestive clinical and family history that allows the diagnosis to be suspected. Increased awareness and improved access to genetic testing are likely to result in more frequent diagnosis of these disorders.
尽管由于双等位基因突变导致的胆管转运蛋白酶严重缺乏被认为是儿童进行性胆汁淤积性肝病的原因已得到充分证实，但越来越多的人认识到，如果存在单个杂合基因突变，可能会发生更轻微的疾病。这种轻度疾病通常最初在成年期出现，其临床表现和组织学表现多种多样。非特异性胆管性胆汁淤积是典型的改变，但现在很清楚，一些基因突变，特别是 ABCB4（编码 MDR3），可引起其他表现，包括早期胆固醇结石形成、胆管损伤和消失、类似于大胆管阻塞的胆管反应，以及在极少数情况下，进行性纤维化。由于这些特征单独存在时可能不明显且无诊断意义，因此通常是胆管损伤模式与提示性临床和家族史相结合，使人们怀疑存在这种诊断。提高认识和改善获得基因检测的机会可能会导致这些疾病的诊断更为频繁。
