肝硬化门静脉高压的病因和非病因治疗

李悦榕; 王民; 何福亮; 赵新颜; 欧晓娟; 尤红; 贾继东; 王宇

doi:10.3969/j.issn.1001-5256.2022.06.003

肝硬化门静脉高压的病因和非病因治疗

DOI: 10.3969/j.issn.1001-5256.2022.06.003

首都医科大学附属北京友谊医院肝病中心，国家消化系统疾病临床医学研究中心，北京 100050

基金项目:

首都卫生发展科研专项 (2022-2-1104);

北京市医院管理局消化内科学科协同发展中心消化专项特色项目 (XXT04)

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: 李悦榕负责选题，收集分析资料，撰写文章; 王民、何福亮、赵新颜、欧晓娟、尤红参与选题，收集资料; 王宇、贾继东拟定写作思路，指导撰写文章，提供修改意见并最终定稿。

详细信息

通信作者:
王宇，wangyuliver@ccmu.edu.cn

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出版历程
- 收稿日期: 2022-04-20
- 录用日期: 2022-05-22
- 出版日期: 2022-06-20

Etiological and non-etiological therapies for cirrhotic portal hypertension

Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing 100050, China

Research funding:

Capital's Funds for Health Improvement and Research (2022-2-1104);

Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXT04)

More Information

Corresponding author: WANG Yu, wangyuliver@ccmu.edu.cn (ORCID: 0000-0003-3025-1073)

摘要

摘要: 高压是肝硬化的严重并发症，是门静脉阻力和门静脉血流量增加的结果。病因和非病因治疗均可在一定程度上有效降低门静脉压力，但在改善预后方面效果欠佳。以降低肝内血管阻力为靶点的新治疗药物可能有助于实现门静脉高压的逆转。本文以肝硬化门静脉高压的发生机制为基础，对目前的药物治疗从病因和非病因治疗两方面进行总结，以期为临床治疗选择提供较全面的理论和循证依据。
- 肝硬化 /
- 门静脉高压 /
- 治疗学
Abstract: Portal hypertension is a serious complication of liver cirrhosis resulting from the increases in portal vascular resistance and portal blood inflow. Both etiological and non-etiological therapies can effectively reduce portal venous pressure to a certain degree, but with an unsatisfactory effect in improving prognosis. New therapeutic drugs targeting the reduction in intrahepatic vascular resistance may help to achieve the reversal of portal hypertension. Based on the pathogenesis of cirrhotic portal hypertension, this article summarizes the current pharmacotherapies from the aspects of etiological and non-etiological therapies, so as to provide a comprehensive theoretical and evidence-based basis for clinical treatment options.
- Liver Cirrhosis /
- Portal Hypertension /
- Therapeutics

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参考文献(34)

[1]	TURCO L, GARCIA-TSAO G, MAGNANI I, et al. Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis[J]. J Hepatol, 2018, 68(5): 949-958. DOI: 10.1016/j.jhep.2017.12.027.
[2]	TURCO L, GARCIA-TSAO G. Portal hypertension: pathogenesis and diagnosis[J]. Clin Liver Dis, 2019, 23(4): 573-587. DOI: 10.1016/j.cld.2019.07.007.
[3]	ABRALDES JG, TREBICKA J, CHALASANI N, et al. Prioritization of therapeutic targets and trial design in cirrhotic portal hypertension[J]. Hepatology, 2019, 69(3): 1287-1299. DOI: 10.1002/hep.30314.
[4]	SELICEAN S, WANG C, GUIXÉ-MUNTET S, et al. Regression of portal hypertension: underlying mechanisms and therapeutic strategies[J]. Hepatol Int, 2021, 15(1): 36-50. DOI: 10.1007/s12072-021-10135-4.
[5]	LAMPERTICO P, INVERNIZZI F, VIGANÒ M, et al. The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study[J]. J Hepatol, 2015, 63(5): 1118-1125. DOI: 10.1016/j.jhep.2015.06.006.
[6]	LI CZ, CHENG LF, LI QS, et al. Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis[J]. World J Gastroenterol, 2013, 19(40): 6849-6856. DOI: 10.3748/wjg.v19.i40.6849.
[7]	HSIEH YH, HUANG HC, CHANG CC, et al. Nucleos(t)ide analogs do not independently influence hepatic fibrosis and portal hypertension beyond viral suppression in CBDL-induced cirrhotic rat[J]. J Pharmacol Exp Ther, 2018, 367(2): 260-266. DOI: 10.1124/jpet.118.250431.
[8]	LENS S, BAIGES A, ALVARADO-TAPIAS E, et al. Clinical outcome and hemodynamic changes following HCV eradication with oral antiviral therapy in patients with clinically significant portal hypertension[J]. J Hepatol, 2020, 73(6): 1415-1424. DOI: 10.1016/j.jhep.2020.05.050.
[9]	WINTERS A, LUEDTKE S, MORELAND A, et al. In hepatitis C virus-related advanced fibrosis and cirrhosis, early decline of liver stiffness following antiviral therapywith DAAs is related to decline in liver inflammation[J]. J Hepatol, 2017, 66(1): S280.
[10]	PAN JJ, BAO F, DU E, et al. Morphometry confirms fibrosis regression from sustained virologic response to direct-acting antivirals for hepatitis C[J]. Hepatol Commun, 2018, 2(11): 1320-1330. DOI: 10.1002/hep4.1228.
[11]	SPAHR L, GOOSSENS N, FURRER F, et al. A return to harmful alcohol consumption impacts on portal hemodynamic changes following alcoholic hepatitis[J]. Eur J Gastroenterol Hepatol, 2018, 30(8): 967-974. DOI: 10.1097/MEG.0000000000001148.
[12]	BERZIGOTTI A, ALBILLOS A, VILLANUEVA C, et al. Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: The SportDiet study[J]. Hepatology, 2017, 65(4): 1293-1305. DOI: 10.1002/hep.28992.
[13]	RODRIGUES SG, MENDOZA YP, BOSCH J. Beta-blockers in cirrhosis: Evidence-based indications and limitations[J]. JHEP Rep, 2020, 2(1): 100063. DOI: 10.1016/j.jhepr.2019.12.001.
[14]	SINAGRA E, PERRICONE G, D'AMICO M, et al. Systematic review with meta-analysis: the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis[J]. Aliment Pharmacol Ther, 2014, 39(6): 557-568. DOI: 10.1111/apt.12634.
[15]	ROCCARINA D, BEST LM, FREEMAN SC, et al. Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis[J]. Cochrane Database Syst Rev, 2021, 4: CD013121. DOI: 10.1002/14651858.CD013121.pub2.
[16]	YANG J, GE K, CHEN L, et al. The efficacy comparison of carvedilol plus endoscopic variceal ligation and traditional, nonselective β-blockers plus endoscopic variceal ligation in cirrhosis patients for the prevention of variceal rebleeding: a meta-analysis[J]. Eur J Gastroenterol Hepatol, 2019, 31(12): 1518-1526. DOI: 10.1097/MEG.0000000000001442.
[17]	de FRANCHIS R, BOSCH J, GARCIA-TSAO G, et al. Baveno Ⅶ - Renewing consensus in portal hypertension[J]. J Hepatol, 2022, 76(4): 959-974. DOI: 10.1016/j.jhep.2021.12.022.
[18]	VILLANUEVA C, ALBILLOS A, GENESCÀ J, et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial[J]. Lancet, 2019, 393(10181): 1597-1608. DOI: 10.1016/S0140-6736(18)31875-0.
[19]	Chinese Society of Hepatology, Chinese Medical Association, XU X, et al. Chinese guidelines on the management of ascites and its related complications in cirrhosis[J]. Hepatol Int, 2019, 13(1): 1-21. DOI: 10.1007/s12072-018-09923-2.
[20]	PARK JH, JUN DW, CHOI J, et al. Low-dose propranolol as secondary prophylaxis for varix bleeding decreases mortality and rebleeding rate in patients with tense ascites[J]. J Clin Med, 2019, 8(5): 573. DOI: 10.3390/jcm8050573.
[21]	XU X, GUO X, de STEFANO V, et al. Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis[J]. Hepatol Int, 2019, 13(4): 468-481. DOI: 10.1007/s12072-019-09951-6.
[22]	XU X, XU S, PRIMIGNANI M, et al. Nonselective β-blockers may progress the thrombosis of portal venous system in cirrhotic patients: a retrospective observational study[J]. Adv Ther, 2020, 37(4): 1452-1463. DOI: 10.1007/s12325-020-01250-z.
[23]	PERROS F, de MAN FS, BOGAARD HJ, et al. Use of β-blockers in pulmonary hypertension[J]. Circ Heart Fail, 2017, 10(4): e003703. DOI: 10.1161/CIRCHEARTFAILURE.116.003703.
[24]	BOSCH J, GRACIA-SANCHO J, ABRALDES JG. Cirrhosis as new indication for statins[J]. Gut, 2020, 69(5): 953-962. DOI: 10.1136/gutjnl-2019-318237.
[25]	GARCIA-TSAO G, ABRALDES JG, BERZIGOTTI A, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases[J]. Hepatology, 2017, 65(1): 310-335. DOI: 10.1002/hep.28906.
[26]	BUNCHORNTAVAKUL C, REDDY KR. Pharmacologic management of portal hypertension[J]. Clin Liver Dis, 2019, 23(4): 713-736. DOI: 10.1016/j.cld.2019.06.004.
[27]	ZHOU X, TRIPATHI D, SONG T, et al. Terlipressin for the treatment of acute variceal bleeding: A systematic review and meta-analysis of randomized controlled trials[J]. Medicine (Baltimore), 2018, 97(48): e13437. DOI: 10.1097/MD.0000000000013437.
[28]	SRIDHARAN K, SIVARAMAKRISHNAN G. Vasoactive agents for the management of variceal bleeding: a mixed treatment comparison network meta-analysis and trial sequential analysis of randomized clinical trials[J]. Drug Res (Stuttg), 2019, 69(9): 487-495. DOI: 10.1055/a-0846-3071.
[29]	FACCIORUSSO A, CHANDAR AK, MURAD MH, et al. Comparative efficacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis[J]. Lancet Gastroenterol Hepatol, 2017, 2(2): 94-102. DOI: 10.1016/S2468-1253(16)30157-1.
[30]	CAVALLIN M, PIANO S, ROMANO A, et al. Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study[J]. Hepatology, 2016, 63(3): 983-992. DOI: 10.1002/hep.28396.
[31]	ISRAELSEN M, KRAG A, ALLEGRETTI AS, et al. Terlipressin versus other vasoactive drugsfor hepatorenal syndrome[J]. Cochrane Database Syst Rev, 2017, 9(9): CD011532. DOI: 10.1002/14651858.CD011532.pub2.
[32]	CAVALLIN M, KAMATH PS, MERLI M, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: arandomized trial[J]. Hepatology, 2015, 62(2): 567-574. DOI: 10.1002/hep.27709.
[33]	CERINI F, VILASECA M, LAFOZ E, et al. Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats[J]. J Hepatol, 2016, 64(4): 834-842. DOI: 10.1016/j.jhep.2015.12.003.
[34]	GUIXÉ-MUNTET S, ZHU CP, XIE WF, et al. Novel therapeutics for portal hypertension and fibrosis in chronic liver disease[J]. Pharmacol Ther, 2020, 215: 107626. DOI: 10.1016/j.pharmthera.2020.107626.