Ge Liang,Zhan Jianghua.Relationship between liver fibrosis and native liver survival in infants with biliary atresia[J].Journal of Clinical Pediatric Surgery,2020,19(02):171-175.[doi:10.3969/j.issn.1671-6353.2020.02.016]
胆道闭锁肝纤维化与自体肝生存关系的研究进展
- Title:
- Relationship between liver fibrosis and native liver survival in infants with biliary atresia
- 分类号:
- R575.7;R657.4+4;R726
- 摘要:
- 胆道闭锁是婴儿期最严重的肝胆系统疾病之一。肝门-空肠吻合术（Kasai手术）是治疗胆道闭锁的主要手段，但术后自体肝长期生存效果不佳，大部分患儿需要通过肝移植来挽救生命。肝纤维化是影响胆道闭锁患儿自体肝生存的重要因素之一，其发生机制复杂，涉及多种信号通路及细胞因子的调控。Kasai手术后胆汁引流不畅、胆管炎发作都会导致肝纤维化进展，进而发生肝硬化。在完善早期诊断、早期手术、通畅引流胆汁及控制胆管炎的同时，还应积极应对患儿肝纤维化的持续进展，以期达到自体肝的长期生存。
- Abstract:
- Biliary atresia (BA) is one of the most serious hepatobiliary diseases during infancy.Kasai portoenterostomy has been a standard treatment for BA.However,its long-term postoperative survival of native liver is poor.Most children require liver transplantation for saving their lives.Liver fibrosis is one of the important influencing factors for native liver survival in BA children.The underlying mechanism is so complex as to involve a large variety of signaling pathways and cytokines.Imperfect biliary drainage and postoperative cholangitis may lead to liver fibrogenesis and even cirrhosis.For achieving long-term native liver survival,we should actively intervene to arrest the progression of liver fibrosis.
参考文献/References:
1 詹江华,王立.小儿肝胆外科现状与展望[J].临床外科杂志,2017,25(12):890-891.DOI:10.3969/j.issn.1005-6483.2017.12.003. Zhan JH,Wang L.Current status and future prospects of pediatric hepatobiliary surgery[J].J Clin Surg,2017,25(12):890-891.DOI:10.3969/j.issn.1005-6483.2017.12.003.
2 Nio M.Japanese Biliary Atresia Registry[J].Pediatr Surge Int,2017,33(12):1319-1325.DOI:10.1007/s00383-017-4160-x.
3 Sasaki H,Tanaka H,Nio M.Current management of long-term survivors of biliary atresia:over 40 years of experience in a single center and review of the literature[J].Pediatr Surg Int,2017,33(12):1-7.DOI:10.1007/s00383-017-4163-7.
4 Qiao G,Li L,Cheng W,et al.Conditional probability of survival in patients with biliary atresia after Kasai portoenterostomy:a Chinese population-based study[J].J Pediatr Surg,2015,50(8):1310-1315.DOI:10.1016/j.jpedsurg.2015.03.062.
5 Davenport M,Parsons C,Tizzard S,et al.Steroids in biliary atresia:single surgeon,single centre,prospective study[J].J Hepatol,2013,59(5):1054-1058.DOI:10.1016/j.jhep.2013.06.012.
6 高婷,詹江华,陈扬,等.JNK2、TIMP-1及Collagen Ⅲ在胆道闭锁肝纤维化中的作用研究[J].临床小儿外科杂志,2017,16(2):127-132.DOI:10.3969/j.issn.1671-6353.2017.02.006. Gao T,Zhan JH,Chen Y,et al.Effects of JNK2,TIMP-1 and collagen Ⅲ on hepatic fibrosis in patients with biliary atresia[J].J Clin Ped Sur,2017,16(2):127-132.DOI:10.3969/j.issn.1671-6353.2017.02.006.
7 丁美云,高婷,卫园园,等.P-Smad 3在胆道闭锁肝纤维化中的作用机制研究[J].临床小儿外科杂志,2016,15(1):29-33.DOI:10.3969/j.issn.1671-6353.2016.01.009. Ding MY,Gao T,Wei YY,et al.The study on Mechanism of P-Smad3 in hepatic fibrosis of biliary atresia[J].J Clin Ped Sur,2016,15(1):29-33.DOI:10.3969/j.issn.1671-6353.2016.01.009.
8 Markovics JA,Araya J,Cambier S,et al.Interleukin-1beta induces increased transcriptional activation of the transforming growth factor beta-activating integrin subunit beta8 through altering chromatin architecture[J].J Biol Chem,2011,286(42):36864-36874.DOI:10.1074/jbc.M111.276790.
9 Burch ML,Zheng W,Little PJ.Smad linker region phosphorylation in the regulation of extracellular matrix synthesis[J].Cell Mol Life Sci,2011,68(1):97-107.DOI:10.1007/s00018-010-0514-4.
10 Brzozowa-Zasada M,Piecuch A,Segiet O,et al.The complex interplay between Notch signaling and Snail1 transcription factor in the regulation of epithelial-mesenchymal transition (EMT)[J].Eur Surg,2015,47(5):218-225.DOI:10.1007/s10353-015-0339-3.
11 Kim DE,Procopio MG,Ghosh S,et al.Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation[J].J Experimental Medicine,2017,214(8):2349-2368.DOI:10.1084/jem.20170724.
12 慕永平,张笑,徐莹,等.Notch信号通路参与大鼠胆汁性肝纤维化肝祖细胞向胆管上皮细胞分化以及肝纤维化进展[J].中华病理学杂志,2017,46(6):400-405.DOI:10.3760/cma.j.issn.0529-5807.2017.06.007. Mu YP,Zhang X,Xu Y,et al.Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat[J].Chin Jo Pathol,2017,46(6):400-405.DOI:10.3760/cma.j.issn.0529-5807.2017.06.007.
13 Huang J,Yu X,Fries JW,et al.MicroRNA function in the profibro genic interplay upon chronic liver disease[J].Int J Mol Sci,2014,15(6):9360-9371.DOI:10.3390/ijms15069360.
14 Wei J,Feng L,Li Z,et al.MicroRNA-21 activates hepatic stellate cells via PTEN/Akt signaling[J].Biomed Pharmacother,2013,67(5):387-392.DOI:10.1016/j.biopha.2013.03.014.
15 Liu HY,Chen YH,Pang SY,et al.MiR-200a/ZEB1 pathway in liver fibrogenesis of biliary atresia[J].International Scholarly and Scientific Research & Innovation,2017,11(2):49-54.
16 Ye Y,Li Z,Feng Q.Downregulation of microRNA-145 may contribute to liver fibrosis in biliary atresia by targeting ADD3[J].PLoS ONE,2017,12(9):e0180896.DOI:10.1371/journal.pone.0180896.
17 Koga H,Wada M,Nakamura H,et al.Factors influencing jaundice-free survival with the native liver in ostportoenterostomy biliary atresia patients:results from a single institution[J].J Pediatr Surg,2013,48(12):2368-2372.DOI:10.1016/j.jpedsurg.2013.08.007.
18 Nakamura H,Koga H,Wada M,et al.Reappraising the portoenterostomy procedure according to sound physiologic/anatomic principles enhances postoperative jaundice clearance in biliary atresia[J].Pediatr Surg Int,2012,28(2):205-209.DOI:10.1007/s00383-011-3019-9.
19 宋亭亭,詹江华,高伟,等.胆道闭锁 Kasai 术后肝脏病理改变的研究[J].中华小儿外科杂志,2014,35(8):603-607.DOI:10.3760/cma.j.issn.0253-3006.2014.08.011. Song TT,Zhan JH,Gao W,et al.Pathological changes of liver in children with biliary atresia after Kasai portoenterstomy[J].Chin J Pediatr Surg,2014,35(8):603-607.DOI:10.3760/cma.j.issn.0253-3006.2014.08.011.
20 熊希倩,詹江华,胡晓丽,等.胆道闭锁患儿肝纤维化及炎症细胞浸润与Kasai术后胆管炎的关系[J].天津医药,2018,46(7):692-695.DOI:10.11958/20180078. Xiong XQ,Zhan JH,Hu XL,et al.Correlation between liver fibrosis inflammatory infiltration and postoperative cholangitis after Kasai operation for children with biliary atresia[J].Tianjin Medical Journal,2018,46(7):692-695.DOI:10.11958/20180078.
21 Wu ET,Chen HL,Ni YH,et al.Bacterial cholangitis in patients with biliary atresia:impact on short-term outcome[J].Pediatr Surg Int,2001,17(5-6):390-395.DOI:10.1007/s003830000573.
22 Hung PY,Chen CC,Chen WJ,et al.Long-term prognosis of patients with biliary atresia:a 25 year summary[J].J Pediatr Gastroenterol Nutr,2006,42(2):190.DOI:10.1097/01.mpg.0000189339.92891.64.
23 Roy P,Chatterjee U,Ganguli M,et al.A histopathological study of liver and biliary remnants with clinical outcome in cases of extrahepatic biliary atresia[J].Indian J Pathol Microbiol,2010,53(1):101-105.DOI:10.4103/0377-4929.59194
24 Salzedas-Netto AA,Chinen E,De Oliveira DF,et al.Grade IV Fibrosis interferes in biliary drainage after Kasai procedure[J].Transplant Proc,2014,46(6):1781-1783.DOI:10.1016/j.transproceed.2014.05.045.
25 董淳强,杨体泉,董昆.胆道闭锁术后早期胆管炎风险因素分析[J].临床小儿外科杂志,2013,12(5):348-353.DOI:10.3969/j.issn.1671-6353.2013.05.002. Dong CQ,Yang TQ,Dong K.Risk factors of postoperative early cholangitis in biliary atresia[J].J Clin Ped Sur,2013,12(5):348-353.DOI:10.3969/j.issn.1671-6353.2013.05.002.
26 Webb NL,Jiwane A,Ooi CY,et al.Clinical significance of liver histology on outcomes in biliary atresia[J].J Paediatr Child Health,2017,53(3):252-256.DOI:10.1111/jpc.13371.
27 Shteyer E,Ramm GA,Xu C,et al.Outcome after portoenterostomy in biliary atresia:pivotal role of degree of liver fibrosis and intensity of stellate cell activation[J].J Pediatr Gastroenterol Nutr,2006,42(1):93-99.
28 Superina R,Magee JC,Brandt ML,et al.The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant-free survival[J].Ann Surg,2011,254(4):577-585.DOI:10.1097/SLA.0b013e3182300950.
29 Davenport M,Puricelli V,Farrant P,et al.The outcome of the older (≥100 days) infant with biliary atresia[J].J Pediatr Surg,2004,39(4):575-581.
30 Lampela H,Kosola S,Heikkilä P,et al.Native liver histology after successful portoenterostomy in biliary atresia[J].J Clin Gastroenterol,2014,48(8):721-728.DOI:10.1097/MCG.0000000000000013.
31 Kerola A,Lampela H,Lohi J,et al.Molecular signature of active fibrogenesis prevails in biliary atresia after successful portoenterostomy[J].Surg,2017,162(3):548-556.DOI:10.1016/j.surg.2017.04.013.
32 余晨,詹江华,高伟,等.胆道闭锁Kasai术后肝移植患儿不同自体肝生存的临床与病理分析[J].临床小儿外科杂志,2017,16(6):552-558.DOI:10.3969/j.issn.1671-6353.2017.06.007. Yu C,Zhan JH,Gao W,et al.Clinicopathological analysis with different native liver survivals for biliary atresia after Kasai[J].J Clin Ped Sur,2017,16(6):552-558.DOI:10.3969/j.issn.1671-6353.2017.06.007.
33 丁美云,詹江华,刘丹丹,等.胆道闭锁肝纤维化分级[J].中华小儿外科杂志,2015,36(11):866-872.DOI:10.3760/cma.j.issn.0253-3006.2015.11.016. Ding MY,Zhan JH,Liu DD,et al.Grading of hepatic fibrosis in biliary atresia[J].Chin J Pediatr Surg,2015,36(11):866-872.DOI:10.3760/cma.j.issn.0253-3006.2015.11.016.
34 管志伟,詹江华,胡晓丽,等.APRI评价胆道闭锁和胆汁淤积综合征肝脏纤维化程度的临床意义[J].中华小儿外科杂志,2012,33(11):815-819.DOI:10.3760/cma.j.issn.0253-3006.2012.11.004. Guan ZW,Zhan JH,Hu XL,et al.The assessment and significance of liver fibrosis in children with biliary atresia[J].Chin J Pediatr Surg,2012,33(11):815-819.DOI:10.3760/cma.j.issn.0253-3006.2012.11.004.
35 Uchida H,Sakamoto S,Kobayashi M,et al.The degree of spleen stiffness measured on acoustic radiation force impulse elastography predicts the severity of portal hypertension in patients with biliary atresia after portoenterostomy[J].J Pediatr Surg,2015,50(4):559-564.DOI:10.1016/j.jpedsurg.2014.12.026.
36 舒俊,陈亚军,张廷冲,等.胆道闭锁术后肝脏FibroScan值预测价值研究[J].中华小儿外科杂志,2014,35(7):514-518.DOI:10.3760/cma.j.issn.0253-3006.2014.07.009. Shu J,Chen YJ,Zhang TC,et al.Predictive values of liver FibroScan in postoperative biliary atresia[J].J Pediatr Surg,2014,35(7):514-518.DOI:10.3760/cma.j.issn.0253-3006.2014.07.009.
37 剧红娟,田晖,李英超,等.声脉冲辐射力成像技术对胆道闭锁肝纤维化的初步研究[J].中华超声影像学杂志,2015,24(5):447-449.DOI:10.3760/cma.j.issn.1004-4477.2015.05.024. Ju HJ,Tian H,Li YC,et al.Preliminary study of hepatic fibrosis in biliary atresia by acoustic radiation for impulse imaging[J].Chin J Ultrasonogr,2015,24(5):447-449.DOI:10.3760/cma.j.issn.1004-4477.2015.05.024.
38 Chen S,Liao B,Zhong Z,et al.Supersonic shearwave elastography in the assessment of liver fibrosis for postoperative patients with biliary atresia[J].Sci Rep,2016,6:31057.DOI:10.1038/srep31057.
相似文献/References:
[1]孙雪,任红霞.胆道闭锁发生与肝纤维化的分子机制研究进展[J].临床小儿外科杂志,2019,18(05):432.[doi:10.3969/j.issn.1671-6353.2019.05.019]
Sun Xue,Ren Hongxia.Advances in molecular mechanisms of biliary atresia and hepatic fibrosis[J].Journal of Clinical Pediatric Surgery,2019,18(02):432.[doi:10.3969/j.issn.1671-6353.2019.05.019]
[2]卫园园,范晋楠,李亚蕊.ADD3基因rs17095355位点多态性与胆道闭锁相关性研究的Meta分析[J].临床小儿外科杂志,2020,19(06):496.[doi:10.3969/j.issn.1671-6353.2020.06.007]
Wei Yuanyuan,Fan Jinnan,Li Yarui.Meta-analysis of the relationship between single nucleotide polymorphism of rs17095355 and biliary atresia[J].Journal of Clinical Pediatric Surgery,2020,19(02):496.[doi:10.3969/j.issn.1671-6353.2020.06.007]
[3]赵一霖,王皓洁,詹江华.胆道闭锁TGFβ1诱导EMT相关通路研究进展[J].临床小儿外科杂志,2021,20(12):1189.[doi:10.12260/lcxewkzz.2021.12.017]
Zhao Yilin,Wang Haojie,Zhan Jianghua.Recent advances of TGFβ1 induced EMT-related signaling pathways in biliary atresia[J].Journal of Clinical Pediatric Surgery,2021,20(02):1189.[doi:10.12260/lcxewkzz.2021.12.017]
[4]阿里木江·阿不都热依木,林峰,王皓洁,等.Notch信号通路活化协同巨噬细胞对胆道闭锁肝纤维化的作用研究[J].临床小儿外科杂志,2021,20(04):376.[doi:10.12260/lcxewkzz.2021.04.014]
Alimujiang·Abudureyimu,Lin Feng,Wang Haojie,et al.Activation of Notch signaling pathway collaborated with macrophages for promoting liver fibrosis in biliary atresia[J].Journal of Clinical Pediatric Surgery,2021,20(02):376.[doi:10.12260/lcxewkzz.2021.04.014]
备注/Memo
收稿日期:2018-10-03。
基金项目:国家自然科学基金项目（编号：81570471）；天津市卫生行业重点攻关项目（编号：14KG129）
通讯作者:詹江华,Email:zhanjianghuatj@163.com