Abstract：
Liver histology in infants with cystic fibrosis (CF) and persistent cholestasis is seldom reported in detail. We extend previous observation of a distinctive intrahepatic cholangiopathy (ICCF) to 3 additional infants homozygous for CFTR pathological variants and a fourth infant with a heterozygous CFTR variant, summarizing our experience in 10 infants with CFTR variants and persistent cholestasis. Cholangiograms demonstrate abnormal extrahepatic ducts in 2 infants with CF, 1 with uniform dilatation interpreted as a choledochal cyst and the other with narrow patent ducts. Liver histology in 3 CF homozygotes had prominent ductular reaction with a focally destructive cholangiolitis (inflammation of small bile ducts). The CFTR heterozygote had generalized portal edema with ductular reaction and paucity but no cholangitis. Cholestasis slowly subsided in all infants. ICCF is characterized by severe ductular reaction, prominent cholangiocyte injury, and multifocal necrotizing cholangiolitis. Local aggregates of portal ceroid might suggest previous bile leakage from damaged ducts. ICCF in liver biopsies from infants with cystic fibrosis and persistent cholestasis is unrelated to the specific CFTR genotype. Liver biopsy findings and intraoperative cholangiogram help rule out biliary atresia. ICCF is an early manifestation of CF, a likely prototype for pathogenesis of cystic fibrosis liver disease later in life.
摘要：
很少详细报道患有囊性纤维化（CF）和持续性胆汁淤积的婴儿的肝组织学。我们将先前观察到的独特肝内胆管病（ICCF）扩展到另外3名CFTR病理变异纯合的婴儿和第四个具有杂合CFTR变异的婴儿。总结我们在10例CFTR变异和持续性胆汁淤积婴儿中的经验。胆管造影显示2例CF婴儿的肝外导管异常，1个具有均匀扩张，被解释为胆总管囊肿，另一个具有狭窄的导管。3个CF纯合子的肝组织学表现出明显的导管反应，伴有局灶性破坏性胆管炎（小胆管炎症）。CFTR杂合子有全身性门静脉水肿，伴有导管反应和缺乏，但无胆管炎。胆汁淤积在所有婴儿中缓慢消退。ICCF的特点是严重的导管反应，突出的胆管细胞损伤，多灶性坏死性胆管炎。门静脉的局部聚集可能表明先前的胆漏来自受损的导管。患有囊性纤维化和持续性胆汁淤积的婴儿的肝活检中的ICCF与特定的CFTR基因型无关。肝活检结果和术中胆管造影有助于排除胆道闭锁。ICCF是CF的早期表现，在以后的生活中，可能是囊性纤维化肝病发病机制的原型。
