PDF下载 ( 1883 KB)
非选择性β受体阻滞剂在肝硬化治疗中的应用
DOI: 10.3969/j.issn.1001-5256.2023.05.028
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：王小泽负责拟定写作思路，资料分析，撰写论文；刘一锋参与检索文献，数据提取，修改论文；杨丽指导撰写文章并最后定稿。
Advances in the application of nonselective β-receptor blockers in treatment of liver cirrhosis
-
摘要: 非选择性β受体阻滞剂(NSBB)是肝硬化患者门静脉高压并发症防治的一线药物，广泛用于食管胃静脉曲张出血的一级预防和二级预防。近年来，在临床显著性门静脉高压(CSPH)患者中，NSBB已被证实还可以预防静脉曲张出血以外的其他肝硬化失代偿事件，如腹水和肝性脑病等。然而，在非CSPH的代偿期患者中，目前的研究证据不支持使用NSBB。尽管目前有可靠数据支持NSBB用于终末期肝硬化，但对于部分顽固性腹水和自发性腹膜炎患者仍存在用药安全问题，给药剂量和时机仍有待研究。本文综述了目前关于肝硬化患者使用NSBB(尤其是卡维地洛)的相关临床研究进展，并总结NSBB在肝硬化全程管理中合理应用的治疗窗口，为临床决策提供依据。
-
关键词:
- 肝硬化 /
- 非选择性β受体阻滞剂 /
- 高血压, 门静脉 /
- 治疗学
Abstract: Nonselective β-receptor blockers (NSBBs) are first-line drugs for the prevention and treatment of complications in cirrhotic patients with portal hypertension and are widely used in the primary and secondary prevention of esophagogastric variceal bleeding. In recent years, studies have shown that in patients with clinically significant portal hypertension (CSPH), NSBBs can used to prevent liver decompensation events besides variceal bleeding, such as ascites and hepatic encephalopathy. However, in patients without CSPH, current research evidence does not support the use of NSBBs. Although reliable data currently support the use of NSBBs in end-stage liver cirrhosis, there are still drug safety issues in patients with refractory ascites and spontaneous bacterial peritonitis, and further studies are needed to explore the dose and timing of administration. This article reviews the clinical research advances in the use of NSBBs (especially carvedilol) in patients with liver cirrhosis and summarizes the therapeutic window used reasonably in the whole-course management of liver cirrhosis, so as to provide a basis for clinical decision-making.-
Key words:
- Liver Cirrhosis /
- Nonselective β-Blockers /
- Hypertension, Portal /
- Therapeutics
-
[1] GRACIA-SANCHO J, MARRONE G, FERNÁNDEZ-IGLESIAS A. Hepatic microcirculation and mechanisms of portal hypertension[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(4): 221-234. DOI: 10.1038/s41575-018-0097-3. [2] LEBREC D, NOUEL O, CORBIC M, et al. Propranolol-a medical treatment for portal hypertension?[J]. Lancet, 1980, 2(8187): 180-182. DOI: 10.1016/s0140-6736(80)90063-x. [3] D'AMICO G, GARCIA-PAGAN JC, LUCA A, et al. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review[J]. Gastroenterology, 2006, 131(5): 1611-1624. DOI: 10.1053/j.gastro.2006.09.013. [4] 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. [5] 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. [6] Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Endoscopy, Chinese Medical Association. Guidelines for the diagnosis and treatment of esophageal and gastric variceal bleeding in cirrhotic portal hypertension[J]. J Clin Hepatol, 2016, 32(2): 203-219. DOI: 10.3969/j.issn.1001-5256.2016.02.002.中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会内镜学分会. 肝硬化门静脉高压食管胃静脉曲张出血的防治指南[J]. 临床肝胆病杂志, 2016, 32(2): 203-219. DOI: 10.3969/j.issn.1001-5256.2016.02.002. [7] 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. [8] de FRANCHIS R, Baveno Ⅵ Faculty. Expanding consensus in portal hypertension: Report of the Baveno Ⅵ Consensus Workshop: Stratifying risk and individualizing care for portal hypertension[J]. J Hepatol, 2015, 63(3): 743-752. DOI: 10.1016/j.jhep.2015.05.022. [9] GLUUD LL, KRAG A. Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults[J]. Cochrane Database Syst Rev, 2012, 8(8): CD004544. DOI: 10.1002/14651858.CD004544.pub2. [10] 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(4): CD013121. DOI: 10.1002/14651858.CD013121.pub2. [11] SHARMA M, SINGH S, DESAI V, et al. Comparison of therapies for primary prevention of esophageal variceal bleeding: a systematic review and network meta-analysis[J]. Hepatology, 2019, 69(4): 1657-1675. DOI: 10.1002/hep.30220. [12] LO GH, CHEN WC, LIN CK, et al. Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding[J]. Hepatology, 2008, 48(2): 580-587. DOI: 10.1002/hep.22358. [13] SARIN SK, WADHAWAN M, AGARWAL SR, et al. Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding[J]. Am J Gastroenterol, 2005, 100(4): 797-804. DOI: 10.1111/j.1572-0241.2005.40468.x. [14] REIBERGER T, ULBRICH G, FERLITSCH A, et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol[J]. Gut, 2013, 62(11): 1634-1641. DOI: 10.1136/gutjnl-2012-304038. [15] SHAH HA, AZAM Z, RAUF J, et al. Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial[J]. J Hepatol, 2014, 60(4): 757-764. DOI: 10.1016/j.jhep.2013.11.019. [16] TRIPATHI D, FERGUSON JW, KOCHAR N, et al. Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed[J]. Hepatology, 2009, 50(3): 825-833. DOI: 10.1002/hep.23045. [17] MCDOWELL HR, CHUAH CS, TRIPATHI D, et al. Carvedilol is associated with improved survival in patients with cirrhosis: a long-term follow-up study[J]. Aliment Pharmacol Ther, 2021, 53(4): 531-539. DOI: 10.1111/apt.16189. [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] RAFAILIDIS S, DEMERTZIDIS C, BALLAS K, et al. Effect of early propranolol administration on portal hypertensive gastropathy in cirrhotic rats[J]. World J Gastroenterol, 2009, 15(34): 4284-4289. DOI: 10.3748/wjg.15.4284. [20] GROSZMANN RJ, GARCIA-TSAO G, BOSCH J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis[J]. N Engl J Med, 2005, 353(21): 2254-2261. DOI: 10.1056/NEJMoa044456. [21] QI XS, BAO YX, BAI M, et al. Nonselective beta-blockers in cirrhotic patients with no or small varices: A meta-analysis[J]. World J Gastroenterol, 2015, 21(10): 3100-3108. DOI: 10.3748/wjg.v21.i10.3100. [22] MERKEL C, MARIN R, ANGELI P, et al. A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis[J]. Gastroenterology, 2004, 127(2): 476-484. DOI: 10.1053/j.gastro.2004.05.004. [23] BHARDWAJ A, KEDARISETTY CK, VASHISHTHA C, et al. Carvedilol delays the progression of small oesophageal varices in patients with cirrhosis: a randomised placebo-controlled trial[J]. Gut, 2017, 66(10): 1838-1843. DOI: 10.1136/gutjnl-2016-311735. [24] ALBILLOS A, ZAMORA J, MARTÍNEZ J, et al. Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis[J]. Hepatology, 2017, 66(4): 1219-1231. DOI: 10.1002/hep.29267. [25] HOLSTER IL, TJWA ET, MOELKER A, et al. Covered transjugular intrahepatic portosystemic shunt versus endoscopic therapy + β-blocker for prevention of variceal rebleeding[J]. Hepatology, 2016, 63(2): 581-589. DOI: 10.1002/hep.28318. [26] SAUERBRUCH T, MENGEL M, DOLLINGER M, et al. Prevention of rebleeding from esophageal varices in patients with cirrhosis receiving small-diameter stents versus hemodynamically controlled medical therapy[J]. Gastroenterology, 2015, 149(3): 660-668. DOI: 10.1053/j.gastro.2015.05.011. [27] LO GH, CHEN WC, WANG HM, et al. Randomized, controlled trial of carvedilol versus nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding[J]. J Gastroenterol Hepatol, 2012, 27(11): 1681-1687. DOI: 10.1111/j.1440-1746.2012.07244.x. [28] STANLEY AJ, DICKSON S, HAYES PC, et al. Multicentre randomised controlled study comparing carvedilol with variceal band ligation in the prevention of variceal rebleeding[J]. J Hepatol, 2014, 61(5): 1014-1019. DOI: 10.1016/j.jhep.2014.06.015. [29] 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. [30] JACHS M, HARTL L, SIMBRUNNER B, et al. Carvedilol achieves higher hemodynamic response and lower rebleeding rates than propranolol in secondary prophylaxis[J]. Clin Gastroenterol Hepatol, 2022. DOI: 10.1016/j.cgh.2022.06.007.[Online ahead of print] [31] SERSTÉ T, MELOT C, FRANCOZ C, et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites[J]. Hepatology, 2010, 52(3): 1017-1022. DOI: 10.1002/hep.23775. [32] BANG UC, BENFIELD T, HYLDSTRUP L, et al. Effect of propranolol on survival in patients with decompensated cirrhosis: a nationwide study based Danish patient registers[J]. Liver Int, 2016, 36(9): 1304-1312. DOI: 10.1111/liv.13119. [33] ROBINS A, BOWDEN A, WATSON W, et al. Beta-blockers in cirrhosis patients with refractory ascites[J]. Hepatology, 2014, 59(5): 2054-2055. DOI: 10.1002/hep.26676. [34] TERGAST TL, KIMMANN M, LASER H, et al. Systemic arterial blood pressure determines the therapeutic window of non-selective beta blockers in decompensated cirrhosis[J]. Aliment Pharmacol Ther, 2019, 50(6): 696-706. DOI: 10.1111/apt.15439. [35] BOSSEN L, KRAG A, VILSTRUP H, et al. Nonselective β-blockers do not affect mortality in cirrhosis patients with ascites: Post Hoc analysis of three randomized controlled trials with 1198 patients[J]. Hepatology, 2016, 63(6): 1968-1976. DOI: 10.1002/hep.28352. [36] ADAY AW, MAYO MJ, ELLIOTT A, et al. The beneficial effect of beta-blockers in patients with cirrhosis, portal hypertension and ascites[J]. Am J Med Sci, 2016, 351(2): 169-176. DOI: 10.1016/j.amjms.2015.11.018. [37] WONG RJ, ROBINSON A, GINZBERG D, et al. Assessing the safety of beta-blocker therapy in cirrhosis patients with ascites: A meta-analysis[J]. Liver Int, 2019, 39(6): 1080-1088. DOI: 10.1111/liv.14040. [38] MANDORFER M, BOTA S, SCHWABL P, et al. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis[J]. Gastroenterology, 2014, 146(7): 1680-1690. DOI: 10.1053/j.gastro.2014.03.005. [39] TREBICKA J, MACNAUGHTAN J, SCHNABL B, et al. The microbiota in cirrhosis and its role in hepatic decompensation[J]. J Hepatol, 2021, 75(Suppl 1): S67-S81. DOI: 10.1016/j.jhep.2020.11.013. [40] VILLANUEVA C, ALBILLOS A, GENESCÀ J, et al. Development of hyperdynamic circulation and response to β-blockers in compensated cirrhosis with portal hypertension[J]. Hepatology, 2016, 63(1): 197-206. DOI: 10.1002/hep.28264. [41] BLASCO-ALGORA S, MASEGOSA-ATAZ J, ALONSO S, et al. Non-selective β-blockers in advanced cirrhosis: a critical review of the effects on overall survival and renal function[J]. BMJ Open Gastroenterol, 2016, 3(1): e000104. DOI: 10.1136/bmjgast-2016-000104. 期刊类型引用(17)
1. 杨文帅，王立坤，董聪慧，武永萍，石栓柱. 瞬时弹性成像技术联合血清游离脂肪酸对非酒精性脂肪性肝病的诊断价值. 转化医学杂志. 2024(09): 1330-1335 . 
百度学术2. 崔会鹏，田昊宇，关琳，李异玲. 代谢相关性脂肪性肝病无创诊断方法研究进展. 胃肠病学和肝病学杂志. 2022(01): 99-103 . 百度学术3. 凡军芳，胡静，耿旭，庄兰艮，时照明. 2型糖尿病患者肝脏受控衰减参数与血清25-羟维生素D的相关性. 中华全科医学. 2021(05): 794-797 . 百度学术4. 陈雅洁，李昭贤，王洋，曹经琳，窦剑. 瞬时弹性成像技术在肝移植围手术期应用的研究进展. 中华器官移植杂志. 2021(08): 501-504 . 百度学术5. 林俊红，林常青，翁娜，刘宴伟. 中年女性高血压体检者体质指数异常与脂肪肝发病率的相关性研究及护理干预. 全科护理. 2020(10): 1212-1214 . 百度学术6. 张晓静，林淑珍，张志安，温美兰. FibroTouch技术在诊断非酒精性脂肪性肝病患者肝脂肪变程度中的应用. 临床医学. 2020(04): 79-80 . 百度学术7. 李萍英，李娟，谢守珍，杨永耿，陆伦根. FibroTouch联合超声和CT检查诊断高原地区非酒精性脂肪性肝病临床应用研究. 实用肝脏病杂志. 2020(06): 817-820 . 百度学术8. 李正鑫，陈洋溢，赵志敏，吕靖，陈高峰，刘成海. 基于肝脏病理学对慢性乙型肝炎肝硬化患者FibroTouch测量值的影响因素分析. 临床肝胆病杂志. 2019(02): 338-344 . 
本站查看9. 陈中淑. 超声检查在诊断脂肪肝方面的临床应用价值. 当代医药论丛. 2019(10): 26-28 . 百度学术10. 何义华，罗建君，文安怡，程志生，余志映，吴舒婷. 二至解酲汤治疗酒精性肝病临床研究. 中医学报. 2018(06): 1099-1102 . 百度学术11. 何妙峰. 腹部B超对健康体检者脂肪肝筛查的价值分析. 深圳中西医结合杂志. 2018(10): 90-91 . 百度学术12. 王晴晴，胡明芬，杨红洁，禹蔚琴，柏保利，匡小林，庄林. B超在慢性HBV携带者合并非酒精性脂肪性肝病诊断中的应用. 肝脏. 2018(08): 723-727 . 百度学术13. 王新. 脂肪肝与病毒性肝炎B超鉴别诊断结果的对比研究. 心理月刊. 2018(04): 47-48 . 百度学术14. 张志伟. 肝功能与血清学指标水平检验对脂肪肝的诊断价值分析. 中外医疗. 2018(34): 11-13 . 百度学术15. 南胜天. CT及B超在脂肪肝临床诊断中应用的价值. 甘肃科技. 2017(07): 102-103 . 百度学术16. 庄小芳，孙洁，王晓波，王燕，吴琦琦，王晓忠. 瞬时弹性成像技术诊断非酒精性脂肪性肝病的性能评估. 临床肝胆病杂志. 2017(12): 2366-2371 . 本站查看17. 杨杰，曹玉芝，徐永升，王雪，刘闯. 373例非酒精性脂肪性肝病FibroTouch检测临床观察. 中国实用医药. 2017(24): 33-34 . 百度学术其他类型引用(12)
-
百度学术
下载:
