原发性胆汁性胆管炎肝移植术后预后研究现状与挑战

陈林; 刘宁; 金晶兰; 蔡艳俊; 许芳; 牛俊奇; 李婉玉

doi:10.3969/j.issn.1001-5256.2021.04.050

原发性胆汁性胆管炎肝移植术后预后研究现状与挑战

DOI: 10.3969/j.issn.1001-5256.2021.04.050

a.
吉林大学第一医院肝胆胰内科，长春 130021
b.
吉林大学第一医院心血管疾病诊治中心，长春 130021

基金项目:

2018年吉林省科技发展计划项目 (20180520116JH);

2017年天晴肝病研究基金 (TQGB20180160);

2017年吉林大学第一医院交叉学科创新项目 (JDYYJC006)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：陈林、刘宁、李婉玉负责课题设计，资料分析，撰写论文；金晶兰、许芳参与收集数据，修改论文；李婉玉、蔡艳俊、牛俊奇负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
陈林(1995—)，女，主要从事原发性胆汁性胆管炎诊断和治疗方面的研究

通信作者:
李婉玉，liwanyu2006@163.com

中图分类号: R575.22
计量
- 文章访问数: 653
- HTML全文浏览量: 367
- PDF下载量: 53
- 被引次数: 0
出版历程
- 收稿日期: 2020-09-22
- 录用日期: 2020-10-09
- 出版日期: 2021-04-20

Research status and challenges in the prognosis of primary biliary cholangitis after liver transplantation

a.
Department of Hepatology, Changchun 130021, China
b.
Department of Cardiology, The First Hospital of Jilin University, Changchun 130021, China

摘要

摘要: 原发性胆汁性胆管炎(PBC)是一种病因尚不明确的慢性胆汁淤积性肝病。熊去氧胆酸、奥贝胆酸等药物治疗不佳的患者最终发展为肝硬化，甚至肝衰竭。目前，肝移植是治疗PBC的唯一有效手段。主要阐述了PBC患者进行肝移植的概况、肝移植术后生存期、并发症、PBC复发以及肝移植治疗前景及挑战，为PBC移植术后的临床转归及治疗提供参考。
- 肝硬化, 胆汁性 /
- 肝移植 /
- 预后 /
- 牛磺熊去氧胆酸
Abstract: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with unknown etiology, and patients with poor response to ursodeoxycholic acid and obeticholic acid may eventually progress to liver cirrhosis and even liver failure. Liver transplantation is the only effective treatment method for PBC at present. This article elaborates on liver transplantation, survival time after liver transplantation, complications, recurrence of PBC after liver transplantation, and prospects and challenges of liver transplantation in patients with PBC, so as to provide a reference for clinical outcome and treatment after liver transplantation for PBC.
- Liver Cirrhosis, Biliary /
- Liver Transplantation /
- Prognosis /
- TAURO-URSODESOXYCHOLIC ACID

HTML全文

表 1 不同病因的肝病患者进行肝移植的术后生存率

病因	1年(%)	3年(%)	5年(%)	10年(%)
PBC^[14-15]	93~94	90~91	82~86	71.2
原发性硬化性胆管炎^[16]	86	79	76	66
自身免疫性肝炎^[17]	88	84	79	68
乙型肝炎^[18]	86		73	59
丙型肝炎^[19]	87	79	72
酒精性肝病^[20]	86		73	59
非酒精性脂肪性肝病^[17]	89	83	77	63
原发性肝癌^[21]	85	75	67

下载: 导出CSV

表 2 不同中心PBC患者进行肝移植后复发情况

作者	年份	地区	例数	定期肝活检	随访时间(年)	5/10年生存率(%)	复发[例(%)]	复发时间(年)
Campsen等^[32]	2009	美国	70	否	7.8(0.3~17)	72/54	18(26)	4.8(0.4~13)
Manousou等^[33]	2010	英国	103	是	9(1~20)	-/-	36(35)	3.7(1~17)
Montano-Loza等^[34]	2010	加拿大	108	否	7.3(0.2~19)	86/76	28(26)	5.8(0.5~16)
Jacob等^[35]	2010	德国	121	是	10(0.4~19)	87/84	18(15)	5(3~10)
Kaneko等^[36]	2012	日本	81	否	6.2(0.1~13.4)	80/-	2(3)	-
Bosch等^[37]	2015	法国	90	是	11.7±5.5	98/94	48(53)	6.4(1~21.6)
Egawa等^[15]	2016	日本	444	否	7.5(0.003~18.8)	76.6/71.2	65(14.6)	5.1

下载: 导出CSV

参考文献(47)

[1]	LLEO A, MARZORATI S, ANAYA JM, et al. Primary biliary cholangitis: A comprehensive overview[J]. Hepatol Int, 2017, 11(6): 485-499. DOI: 10.1007/s12072-017-9830-1.
[2]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis) (2015)[J]. J Clin Hepatol, 2015, 31(12): 1980-1988. DOI: 10.3969/j.issn.1001-5256.2015.12.004. 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J]. 临床肝胆病杂志, 2015, 31(12): 1980-1988. DOI: 10.3969/j.issn.1001-5256.2015.12.004.
[3]	XIA ZY, HAN T, MENG HJ. Early immunosuppression combined with ursodeoxycholic acid in the treatment of primary biliary cirrhosis[J]. Chin J Med Offic, 2020, 48(1): 97-98, 101. DOI: 10.16680/j.1671-3826.2020.01.33. 夏志勇, 韩涛, 孟红军. 早期免疫抑制联合熊去氧胆酸治疗原发性胆汁性肝硬化临床疗效[J]. 临床军医杂志, 2020, 48(1): 97-98, 101. DOI: 10.16680/j.1671-3826.2020.01.33.
[4]	NEVENS F, ANDREONE P, MAZZELLA G, et al. A Placebo-controlled trial of obeticholic acid in primary biliary cholangitis[J]. N Engl J Med, 2016, 375(7): 631-643. DOI: 10.1056/NEJMoa1509840.
[5]	HIRSCHFIELD GM, MASON A, LUKETIC V, et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid[J]. Gastroenterology, 2015, 148(4): 751-761.e8. DOI: 10.1053/j.gastro.2014.12.005.
[6]	SHAH RA, KOWDLEY KV. Current and potential treatments for primary biliary cholangitis[J]. Lancet Gastroenterol Hepatol, 2020, 5(3): 306-315. DOI: 10.1016/S2468-1253(19)30343-7.
[7]	CHASCSA D, CAREY EJ, LINDOR KD. Old and new treatments for primary biliary cholangitis[J]. Liver Int, 2017, 37(4): 490-499. DOI: 10.1111/liv.13294.
[8]	XU L, ZHENG YQ, SHI Z, et al. Influencing factors for the prognosis of primary biliary cholangitis[J]. J Clin Hepatol, 2019, 35(8): 1870-1873. DOI: 10.3969/j.issn.1001-5256.2019.08.050. 徐黎, 郑玥琪, 时桢, 等. 原发性胆汁性胆管炎预后的影响因素[J]. 临床肝胆病杂志, 2019, 35(8): 1870-1873. DOI: 10.3969/j.issn.1001-5256.2019.08.050.
[9]	SCHÖNING W, SCHMEDING M, ULMER F, et al. Liver transplantation for patients with cholestatic liver diseases[J]. Viszeralmedizin, 2015, 31(3): 194-198. DOI: 10.1159/000431017.
[10]	SUN CK, CHEN CL, CONCEJERO AM, et al. Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: A single-center Asian experience[J]. Clin Transplant, 2011, 25(1): 47-53. DOI: 10.1111/j.1399-0012.2010.01288.x.
[11]	CARBONE M, NEUBERGER JM. Autoimmune liver disease, autoimmunity and liver transplantation[J]. J Hepatol, 2014, 60(1): 210-223. DOI: 10.1016/j.jhep.2013.09.020.
[12]	DICKSON ER, GRAMBSCH PM, FLEMING TR, et al. Prognosis in primary biliary cirrhosis: Model for decision making[J]. Hepatology, 1989, 10(1): 1-7. DOI: 10.1002/hep.1840100102.
[13]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of cholestatic liver diseases[J]. J Hepatol, 2009, 51(2): 237-267. DOI: 10.1016/j.jhep.2009.04.009.
[14]	LIBERAL R, ZEN Y, MIELI-VERGANI G, et al. Liver transplantation and autoimmune liver diseases[J]. Liver Transpl, 2013, 19(10): 1065-1077. DOI: 10.1002/lt.23704.
[15]	EGAWA H, SAKISAKA S, TERAMUKAI S, et al. Long-term outcomes of living-donor liver transplantation for primary biliary cirrhosis: A Japanese multicenter study[J]. Am J Transplant, 2016, 16(4): 1248-1257. DOI: 10.1111/ajt.13583.
[16]	MOTTERSHEAD M, NEUBERGER J. Transplantation in autoimmune liver diseases[J]. World J Gastroenterol, 2008, 14(21): 3388-3395. DOI: 10.3748/wjg.14.3388.
[17]	THULUVATH PJ, HANISH S, SAVVA Y. Liver transplantation in cryptogenic cirrhosis: Outcome comparisons between NASH, alcoholic, and AIH cirrhosis[J]. Transplantation, 2018, 102(4): 656-663. DOI: 10.1097/TP.0000000000002030.
[18]	BURRA P, GERMANI G, ADAM R, et al. Liver transplantation for HBV-related cirrhosis in Europe: An ELTR study on evolution and outcomes[J]. J Hepatol, 2013, 58(2): 287-296. DOI: 10.1016/j.jhep.2012.10.016.
[19]	CHOLANKERIL G, WONG RJ, HU M, et al. Liver transplantation for nonalcoholic steatohepatitis in the US: Temporal trends and outcomes[J]. Dig Dis Sci, 2017, 62(10): 2915-2922. DOI: 10.1007/s10620-017-4684-x.
[20]	ADAM R, KARAM V, DELVART V, et al. Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR)[J]. J Hepatol, 2012, 57(3): 675-688. DOI: 10.1016/j.jhep.2012.04.015.
[21]	KOSITAMONGKOL P, SANPHASITVONG V, SIRIVATANAUKSORN Y, et al. Outcome of liver transplantation in hepatocellular carcinoma patients at Siriraj Hospital[J]. Transplant Proc, 2017, 49(5): 1114-1117. DOI: 10.1016/j.transproceed.2017.03.047.
[22]	SINGH A, FRITZE D, MANSOURI M, et al. Characteristics and outcomes of liver transplantation for primary biliary cholangitis in young patients: Analysis of the United Network for organ sharing database[J]. Transplantation, 2019, 103(6): 1191-1198. DOI: 10.1097/TP.0000000000002501.
[23]	GR T M, LEWANDOWSKI Z, PATKOWSKI W, et al. Relevance of male-to-female sex mismatch in liver transplantation for primary biliary cirrhosis[J]. Ann Transplant, 2015, 20: 116-123. DOI: 10.12659/AOT.892394.
[24]	HASEGAWA K, SUGAWARA Y, IMAMURA H, et al. Living donor liver transplantation for primary biliary cirrhosis: Petrospective analysis of 50 patients in a single center[J]. Transpl Int, 2005, 18(7): 794-799. DOI: 10.1111/j.1432-2277.2005.00129.x.
[25]	COELHO J, LEITE LO, MOLENA A, et al. Biliary complications after liver transplantation[J]. Arq Bras Cir Dig, 2017, 30(2): 127-131. DOI: 10.1590/0102-6720201700020011.
[26]	ABAD CL, LAHR BD, RAZONABLE RR. Epidemiology and risk factors for infection after living donor liver transplantation[J]. Liver Transpl, 2017, 23(4): 465-477. DOI: 10.1002/lt.24739.
[27]	NEMES B, GÁMÁN G, DOROS A. Biliary complications after liver transplantation[J]. Expert Rev Gastroenterol Hepatol, 2015, 9(4): 447-466. DOI: 10.1586/17474124.2015.967761.
[28]	LEVITSKY J, GOLDBERG D, SMITH AR, et al. Acute rejection increases risk of graft failure and death increcent liver transplant recipients[J]. Clin Gastroenterol Hepatol, 2017, 15(4): 584-593.e2. DOI: 10.1016/j.cgh.2016.07.035.
[29]	UEMURA T, IKEGAMI T, SANCHEZ EQ, et al. Late acute rejection after liver transplantation impacts patient survival[J]. Clin Transplant, 2008, 22(3): 316-323. DOI: 10.1111/j.1399-0012.2007.00788.x.
[30]	MILKIEWICZ P, GUNSON B, SAKSENA S, et al. Increased incidence of chronic rejection in adult patients transplanted for autoimmune hepatitis: Assessment of risk factors[J]. Transplantation, 2000, 70(3): 477-480. DOI: 10.1097/00007890-200008150-00014.
[31]	NEUBERGER J, PORTMANN B, MACDOUGALL BR, et al. Recurrence of primary biliary cirrhosis after liver transplantation[J]. N Engl J Med, 1982, 306(1): 1-4. DOI: 10.1056/NEJM198201073060101.
[32]	CAMPSEN J, ZIMMERMAN M, TROTTER J, et al. Liver transplantation for primary biliary cirrhosis: Results of aggressive corticosteroid withdrawal[J]. Transplant Proc, 2009, 41(5): 1707-1712. DOI: 10.1016/j.transproceed.2008.10.095.
[33]	MANOUSOU P, ARVANITI V, TSOCHATZIS E, et al. Primary biliary cirrhosis after liver transplantation: Influence of immunosuppression and human leukocyte antigen locus disparity[J]. Liver Transpl, 2010, 16(1): 64-73. DOI: 10.1002/lt.21960.
[34]	MONTANO-LOZA AJ, WASILENKO S, BINTNER J, et al. Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation[J]. Am J Transplant, 2010, 10(4): 852-858. DOI: 10.1111/j.1600-6143.2009.03006.x.
[35]	JACOB DA, HAASE E, KLEIN F, et al. Donor influence on outcome in patients undergoing liver transplant for primary biliary cirrhosis[J]. Exp Clin Transplant, 2010, 8(2): 104-110. http://europepmc.org/abstract/MED/20565366
[36]	KANEKO J, SUGAWARA Y, TAMURA S, et al. Long-term outcome of living donor liver transplantation for primary biliary cirrhosis[J]. Transpl Int, 2012, 25(1): 7-12. DOI: 10.1111/j.1432-2277.2011.01336.x.
[37]	BOSCH A, DUMORTIER J, MAUCORT-BOULCH D, et al. Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence[J]. J Hepatol, 2015, 63(6): 1449-1458. DOI: 10.1016/j.jhep.2015.07.038.
[38]	NEUBERGER J. Recurrent primary biliary cirrhosis[J]. Liver Transpl, 2003, 9(6): 539-546. DOI: 10.1053/jlts.2003.50096.
[39]	AKAMATSU N, SUGAWARA Y. Primary biliary cirrhosis and liver transplantation[J]. Intractable Rare Dis Res, 2012, 1(2): 66-80. DOI: 10.5582/irdr.2012.v1.2.66.
[40]	CARBONE M, NEUBERGER J. Liver transplantation in PBC and PSC: Indications and disease recurrence[J]. Clin Res Hepatol Gastroenterol, 2011, 35(6-7): 446-454. DOI: 10.1016/j.clinre.2011.02.007.
[41]	CARBONE M, MELLS GF, ALEXANDER GJ, et al. Calcineurin inhibitors and the IL12A locus influence risk of recurrent primary biliary cirrhosis after liver transplantation[J]. Am J Transplant, 2013, 13(4): 1110-1111. DOI: 10.1111/ajt.12132.
[42]	SHIBA H, WAKIYAMA S, FUTAGAWA Y, et al. Switching from tacrolimus to cyclosporine A to prevent primary biliary cirrhosis recurrence after living-donor liver transplantation[J]. Int Surg, 2013, 98(2): 156-159. DOI: 10.9738/CC188.
[43]	BHANJI RA, MASON AL, GIRGIS S, et al. Liver transplantation for overlap syndromes of autoimmune liver diseases[J]. Liver Int, 2013, 33(2): 210-219. DOI: 10.1111/liv.12027.
[44]	GAUTAM M, CHERUVATTATH R, BALAN V. Recurrence of autoimmune liver disease after liver transplantation: A systematic review[J]. Liver Transpl 2006, 12: 1813-1824. DOI: 10.1002/lt.20910.
[45]	SILVEIRA MG, TALWALKAR JA, LINDOR KD, et al. Recurrent primary biliary cirrhosis after liver transplantation[J]. Am J Transplant, 2010, 10(4): 720-726. DOI: 10.1111/j.1600-6143.2010.03038.x.
[46]	CHARATCHAROENWITTHAYA P, PIMENTEL S, TALWALKAR JA, et al. Long-term survival and impact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation[J]. Liver Transpl, 2007, 13(9): 1236-1245. DOI: 10.1002/lt.21124.
[47]	RACZYNSKA J, HABIOR A, PACZEK L, et al. Primary biliary cirrhosis in the era of liver transplantation[J]. Ann Transplant, 2014, 19: 488-493. DOI: 10.12659/AOT.890753.