Kurbegov Amethyst C, Setchell Kenneth D R, Haas Joel E, Mierau Gary W, Narkewicz Michael, Bancroft John D, Karrer Frederick, Sokol Ronald J
Pediatric Liver Center and Liver Transplantation Program, Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, Denver, Colorado, USA.
Gastroenterology. 2003 Oct;125(4):1227-34. doi: 10.1016/s0016-5085(03)01199-5.
Progressive familial intrahepatic cholestasis (PFIC) is characterized by pruritus, intrahepatic cholestasis, low serum gamma-glutamyltransferase levels, and characteristic "Byler bile" on electron microscopy. Many patients require liver transplantation, but partial external biliary diversion (PEBD) has shown therapeutic promise. However, the effect of PEBD on liver morphology and bile composition has not been evaluated.
We reviewed liver biopsy specimens from 3 children with low gamma-glutamyltransferase PFIC before and after PEBD. Follow-up liver biopsies were performed 9-60 months after PEBD. Light and electron microscopic features were scored blindly. Biliary bile acid composition was analyzed by gas chromatography-mass spectrometry before and after PEBD in 1 patient and after PEBD in 2 patients.
Following PEBD, all patients improved clinically. Preoperative biopsy specimens showed characteristic features of PFIC, including portal fibrosis, chronic inflammation, cholestasis, giant cell transformation, and central venous mural sclerosis. Ultrastructural findings included coarse, granular canalicular Byler bile, effaced canalicular microvilli, and proliferative pericanalicular microfilaments. Following diversion, histology showed almost complete resolution of cholestasis, portal fibrosis, and inflammation with resolution of ultrastructural abnormalities. Biliary bile acids before PEBD consisted predominantly of cholic acid. After PEBD, the proportion of chenodeoxycholic acid increased significantly in 1 patient and was above the PFIC range in a second patient.
The resolution of hepatic morphologic abnormalities following PEBD supports PEBD as an effective therapy for PFIC. The improved biliary bile acid composition suggests enhanced bile acid secretion after PEBD, perhaps by induction of alternative canalicular transport proteins.
进行性家族性肝内胆汁淤积症（PFIC）的特征为瘙痒、肝内胆汁淤积、血清γ-谷氨酰转移酶水平降低以及电子显微镜下特征性的“Byler胆汁”。许多患者需要肝移植，但部分外引流术（PEBD）已显示出治疗前景。然而，PEBD对肝脏形态和胆汁成分的影响尚未得到评估。
我们回顾了3例γ-谷氨酰转移酶水平低的PFIC患儿在PEBD前后的肝活检标本。在PEBD后9至60个月进行随访肝活检。对光镜和电镜特征进行盲法评分。对1例患者在PEBD前后以及2例患者在PEBD后通过气相色谱-质谱分析法分析胆汁酸成分。
PEBD后，所有患者临床症状均有改善。术前活检标本显示PFIC的特征性表现，包括门脉纤维化、慢性炎症、胆汁淤积、巨细胞转化和中央静脉壁硬化。超微结构发现包括粗糙的、颗粒状的胆小管Byler胆汁、消失的胆小管微绒毛和增生的胆小管周围微丝。引流术后，组织学显示胆汁淤积、门脉纤维化和炎症几乎完全消退，超微结构异常也得到缓解。PEBD前胆汁酸主要由胆酸组成。PEBD后，1例患者鹅去氧胆酸比例显著增加，另1例患者该比例高于PFIC范围。
PEBD后肝脏形态学异常的消退支持PEBD作为PFIC的有效治疗方法。胆汁酸成分的改善表明PEBD后胆汁酸分泌增加，可能是通过诱导替代性胆小管转运蛋白实现的。
