Native Liver Histology After Successful Portoenterostomy in Biliary Atresia
Native Liver Histology After Successful Portoenterostomy in Biliary Atresia
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DOI：
10.1097/mcg.0000000000000013
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发表时间：
2014-09-01
影响因子：
2.9
通讯作者：
Pakarinen, Mikko P.
中科院分区：
文献类型：
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作者：
Lampela, Hanna;Kosola, Silja;Pakarinen, Mikko P.
背景：胆道闭锁是儿童肝移植最常见的适应症。成功的门肠造口术 (PE) 对自体肝脏组织学的影响仍不清楚。 目的：我们评估了成功 PE 后自体肝脏组织学的变化与肝功能和临床结果的关系。方法：总共，在 PE 时（n = 30）、成功 PE 后 4.2 年（n = 23）和失败 PE 后 1.1 年（n = 17）对 44 名胆道闭锁患者进行了 70 例自体肝活检，并且检查胆汁淤积、纤维化、炎症和细胞角蛋白 7 (CK7) 免疫阳性（慢性胆汁淤积）。十个移植供体肝脏作为对照。结果：成功PE后[活检时血清胆红素11（2至35）mmol/L]，83%的患者组织学天然肝胆汁淤积完全消失，门静脉炎症显着减少。然而，纤维化增强[Metavir 2 期 (1-4) 与 4 期 (1-4)]、胆管增殖[2 级 (1-2) 与 1 (0-2)] 和门静脉 CK7 免疫染色[1 级 (0-2) 与 1 (0-4)] 分别在 100%、87% 和 61% 的受试者中持续存在。 Metavir 纤维化分期相当于 52% 患者的肝硬化（4 期），与门静脉高压的存在相关，并与血清结合胆红素（r = 0.601，P = 0.002）、胆管增殖（r = 0.657，P = 0.001）和 CK7 阳性（r = 0.657，P = 0.001）相关。天冬氨酸转移酶与血小板比率指数预测天然肝纤维化和食管静脉曲张的发展。 PE 处的纤维化和门静脉炎症程度与天然肝脏存活无关。结论：尽管胆汁淤积得到解决并且炎症减少，但成功 PE 后胆管增殖、门静脉周围 CK7 免疫染色和纤维化仍然存在。纤维化与生化胆汁淤积、胆管增殖、CK7 免疫阳性（慢性胆汁淤积）和门静脉高压的发生有关。
Background: Biliary atresia is the most common indication for childhood liver transplantation. The effects of successful portoenterostomy (PE) on native liver histology remain unclear.Aims: We assessed changes in native liver histology after a successful PE in relation to liver function and clinical outcomes.Methods: In total, 70 native liver biopsies of 44 biliary atresia patients were obtained at PE (n = 30), 4.2 years after successful PE (n = 23) and 1.1 years after failed PE (n = 17), and reviewed for cholestasis, fibrosis, inflammation, and cytokeratin 7 (CK7) immunopositivity (chronic cholestasis). Ten transplant donor livers served as controls.Results: After a successful PE [serum bilirubin 11 (2 to 35) mmol/L at biopsy], histologic native liver cholestasis completely resolved in 83% of the patients and portal inflammation significantly decreased. Nevertheless, enhanced fibrosis [Metavir stage 2 (1-4) vs. 4 (1-4)], bile duct proliferation [grade 2 (1-2) vs. 1 (0-2)], and periportal CK7 immunostaining [grade 1 (0-2) vs. 1 (0-4)] persisted in 100%, 87%, and 61% of subjects, respectively. Metavir fibrosis stage corresponded cirrhosis (stage 4) in 52% of the patients, associated with the presence of portal hypertension, and correlated with serum-conjugated bilirubin (r = 0.601, P = 0.002), bile duct proliferation (r = 0.657, P = 0.001), and CK7 positivity (r = 0.657, P = 0.001). Aspartate transferase to platelet ratio index predicted native liver fibrosis and development of esophageal varices. The degree of fibrosis and portal inflammation at PE were unrelated to native liver survival.Conclusions: Despite resolution of cholestasis and decreasing inflammation, bile duct proliferation, periportal CK7 immunostaining, and fibrosis persist after successful PE. Fibrosis is associated with biochemical cholestasis, bile duct proliferation, CK7 immunopositivity (chronic cholestasis), and development of portal hypertension.