PDF下载 ( 1714 KB)
肝细胞癌系统治疗药物对门静脉高压的影响
DOI: 10.3969/j.issn.1001-5256.2023.07.002
利益冲突声明: 本文不存在任何利益冲突。
作者贡献声明: 康文迪负责课题设计，文献检索，撰写论文；骆银根参与修改论文；杨正强、李肖负责拟定写作思路，指导撰写文章并最后定稿。
Effect of systemic therapeutic drugs for hepatocellular carcinoma on portal hypertension
-
摘要: 我国肝细胞癌(HCC)患者绝大多数来源于乙型肝炎肝硬化，而90%的肝硬化患者都会发生门静脉高压，HCC患者中合并门静脉高压占15%~30%。门静脉高压症是一组以门静脉压力升高、门体侧支循环形成为特征的临床综合征，是肝硬化最主要的并发症之一。HCC与门静脉高压两者之间相互影响，门静脉高压严重影响HCC患者预后。HCC系统治疗方案的发展，为中晚期HCC患者提供了更多的治疗选择，主要包括分子靶向药物治疗、免疫治疗和化疗等。各种HCC系统治疗药物对门静脉高压的影响也不尽相同，本文就HCC常用系统治疗药物对于门静脉高压的影响予以综述。Abstract: The vast majority of patients with hepatocellular carcinoma (HCC) in China originate from hepatitis B cirrhosis, while 90% of cirrhotic patients may develop portal hypertension, and the HCC patients with portal hypertension account for 15%-30%. Portal hypertension is a group of clinical syndromes characterized by elevated portal venous pressure and formation of portal-systemic collateral circulation, and it is one of the most important complications of liver cirrhosis. HCC and portal hypertension affect each other, and portal hypertension seriously affects the prognosis of HCC patients. The development of systemic treatment regimens for HCC provides more treatment options for patients with advanced HCC, including molecular-targeted drug therapy, immunotherapy, and chemotherapy. Different systemic therapeutic drugs for HCC have different impacts on portal hypertension, and this article reviews the effect of commonly used systemic therapeutic drugs for HCC on portal hypertension.
-
Key words:
- Carcinoma, Hepatocellular /
- Portal Hypertension /
- Therapeutics
-
[1] VOGEL A, MEYER T, SAPISOCHIN G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400(10360): 1345-1362. DOI: 10.1016/S0140-6736(22)01200-4. [2] China Anti Cancer Association Liver Cancer Professional Committee of International Hepatobiliary Pancreatic Association China Branch, China Research Hospital Hepatobiliary Surgery Professional Committee, China Research Hospital Virus and Tumor Professional Committee. Chinese Expert Consensus on antiviral therapy for hepatitis B virus related hepatocellular carcinoma (2023 version)[J]. Chin Hepatol, 2023, 28(1): 1-10. DOI: 10.3969/j.issn.1008-1704.2023.01.001.国际肝胆胰协会中国分会中国抗癌协会肝癌专业委员会, 中国研究型医院肝胆外科专业委员会, 中国研究型医院病毒与肿瘤专业委员会. 乙型肝炎病毒相关肝细胞癌抗病毒治疗中国专家共识(2023年版)[J]. 肝脏, 2023, 28(1): 1-10. DOI: 10.3969/j.issn.1008-1704.2023.01.001. [3] LI T, CHEN H. Liver transplantation for the treatment of portal hypertension in liver cirrhosis[J]. J Surg Concepts Pract, 2021, 26(3): 189-194. DOI: 10.16139/j.1007-9610.2021.03.002.李涛, 陈皓. 肝硬化门静脉高压症的肝移植治疗[J]. 外科理论与实践, 2021, 26(3): 189-194. DOI: 10.16139/j.1007-9610.2021.03.002. [4] WANG WD. Diagnosis and treatment of hepatocellular carcinoma with portal hypertension[J]. World Chin J Dig, 2018, 26(24): 1429-1433. DOI: 10.11569/wcjd.v26.i24.1429.王卫东. 肝癌合并门静脉高压症的诊治现状[J]. 世界华人消化杂志, 2018, 26(24): 1429-1433. DOI: 10.11569/wcjd.v26.i24.1429. [5] SANGRO B, SAROBE P, HERVÁS-STUBBS S, et al. Advances in immunotherapy for hepatocellular carcinoma[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(8): 525-543. DOI: 10.1038/s41575-021-00438-0. [6] BRUIX J, QIN S, MERLE P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2017, 389(10064): 56-66. DOI: 10.1016/S0140-6736(16)32453-9. [7] LLOVET J M, RICCI S, MAZZAFERRO V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4): 378-390. [8] KUDO M, FINN RS, QIN S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173. DOI: 10.1016/S0140-6736(18)30207-1. [9] ABOU-ALFA GK, MEYER T, CHENG AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma[J]. N Engl J Med, 2018, 379(1): 54-63. DOI: 10.1056/NEJMoa1717002. [10] GANA JC, SERRANO CA, LING SC. Angiogenesis and portal- systemic collaterals in portal hypertension[J]. Ann Hepatol, 2016, 15(3): 303-313. DOI: 10.5604/16652681.1198799. [11] ZHU Y, CHENG Y, LI AM, et al. Therapeutic effect of sorafenib on portal hypertension: research progress and mechanisms[J]. J South Med Univ, 2014, 34(1): 133-136. DOI: 10.12122/j.issn.1673-4254.2014.01.030.朱云, 程旸, 李爱民, 等. 索拉非尼对门静脉高压症的治疗作用及其机制[J]. 南方医科大学学报, 2014, 34(1): 133- 136. DOI: 10.12122/j.issn.1673-4254.2014.01.030. [12] THABUT D, ROUTRAY C, LOMBERK G, et al. Complementary vascular and matrix regulatory pathways underlie the beneficial mechanism of action of sorafenib in liver fibrosis[J]. Hepatology, 2011, 54(2): 573-585. DOI: 10.1002/hep.24427. [13] REIBERGER T, ANGERMAYR B, SCHWABL P, et al. Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats[J]. J Hepatol, 2009, 51(5): 865-873. DOI: 10.1016/j.jhep.2009.06.024. [14] MEJIAS M, GARCIA-PRAS E, TIANI C, et al. Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats[J]. Hepatology, 2009, 49(4): 1245-1256. DOI: 10.1002/hep.22758. [15] HENNENBERG M, TREBICKA J, STARK C, et al. Sorafenib targets dysregulated Rho kinase expression and portal hypertension in rats with secondary biliary cirrhosis[J]. Br J Pharmacol, 2009, 157(2): 258-270. DOI: 10.1111/j.1476-5381.2009.00158.x. [16] CORIAT R, GOUYA H, MIR O, et al. Reversible decrease of portal venous flow in cirrhotic patients: a positive side effect of sorafenib[J]. PLoS One, 2011, 6(2): e16978. DOI: 10.1371/journal.pone.0016978. [17] HIDAKA H, NAKAZAWA T, KANEKO T, et al. Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study[J]. J Gastroenterol, 2012, 47(9): 1030-1035. DOI: 10.1007/s00535-012-0563-6. [18] PINTER M, SIEGHART W, REIBERGER T, et al. The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma-a pilot study[J]. Aliment Pharmacol Ther, 2012, 35(1): 83-91. DOI: 10.1111/j.1365-2036.2011.04896.x. [19] D'AMICO M, MEJIAS M, GARCIA-PRAS E, et al. Effects of the combined administration of propranolol plus sorafenib on portal hypertension in cirrhotic rats[J]. Am J Physiol Gastrointest Liver Physiol, 2012, 302(10): G1191-G1198. DOI: 10.1152/ajpgi.00252.2011. [20] KUDO M. Lenvatinib may drastically change the treatment landscape of hepatocellular carcinoma[J]. Liver Cancer, 2018, 7(1): 1-19. DOI: 10.1159/000487148. [21] OHYA K, KAWAOKA T, NAMBA M, et al. Early changes in ammonia levels and liver function in patients with advanced hepatocellular carcinoma treated by lenvatinib therapy[J]. Sci Rep, 2019, 9(1): 12101. DOI: 10.1038/s41598-019-48045-z. [22] ALLAIRE M, RUDLER M, THABUT D. Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses[J]. Liver Int, 2021, 41(8): 1734-1743. DOI: 10.1111/liv.14977. [23] HIDAKA H, UOJIMA H, NAKAZAWA T, et al. Portal hemodynamic effects of lenvatinib in patients with advanced hepatocellular carcinoma: A prospective cohort study[J]. Hepatol Res, 2020, 50(9): 1083-1090. DOI: 10.1111/hepr.13531. [24] USCHNER FE, SCHUELLER F, NIKOLOVA I, et al. The multikinase inhibitor regorafenib decreases angiogenesis and improves portal hypertension[J]. Oncotarget, 2018, 9(90): 36220-36237. DOI: 10.18632/oncotarget.26333. [25] APTE RS, CHEN DS, FERRARA N. VEGF in signaling and disease: beyond discovery and development[J]. Cell, 2019, 176(6): 1248-1264. DOI: 10.1016/j.cell.2019.01.021. [26] ROSMORDUC O. Antiangiogenic therapies in portal hypertension: a breakthrough in hepatology[J]. Gastroenterol Clin Biol, 2010, 34(8-9): 446-449. DOI: 10.1016/j.gcb.2010.05.007. [27] LARREY E, CAMPION B, EVAIN M, et al. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC[J]. Liver Int, 2022, 42(12): 2843-2854. DOI: 10.1111/liv.15458. [28] CAMPION B, LARREY E, WAGNER M, et al. Portal hypertension, advanced hepatocellular carcinoma and therapy by atezolizumab-bevacizumab: A "menage à trois"![J]. Clin Res Hepatol Gastroenterol, 2022, 46(2): 101785. DOI: 10.1016/j.clinre.2021.101785. [29] FURUSAWA A, NAGANUMA A, SUZUKI Y, et al. Two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma[J]. Clin J Gastroenterol, 2022, 15(2): 451-459. DOI: 10.1007/s12328-022-01605-9. [30] SUZUKI H, IWAMOTO H, SHIMOSE S, et al. Case Report: Exacerbation of varices following atezolizumab plus bevacizumab treatment of hepatocellular carcinoma: A case series and literature review[J]. Front Oncol, 2022, 12: 948293. DOI: 10.3389/fonc.2022.948293. [31] QIN S, BAI Y, LIM HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia[J]. J Clin Oncol, 2013, 31(28): 3501-3508. DOI: 10.1200/JCO.2012.44.5643. [32] QIN S, CHENG Y, LIANG J, et al. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study[J]. Oncologist, 2014, 19(11): 1169-1178. DOI: 10.1634/theoncologist.2014-0190. [33] Chinese Society of Clinical Oncology. Dignosis and treatment guidelines for primary liver cancer 2022[M]. People's Health Publishing House, 2022: 90-91.中国临床肿瘤协会(CSCO). 原发性肝癌诊疗指南2022[M]. 人民卫生出版社, 2022: 90-91. [34] LYU N, WANG X, LI JB, et al. Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: a biomolecular exploratory, randomized, phase iii trial (FOHAIC-1)[J]. J Clin Oncol, 2022, 40(5): 468-480. DOI: 10.1200/JCO.21.01963. [35] SLADE JH, ALATTAR ML, FOGELMAN DR, et al. Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury[J]. Clin Colorectal Cancer, 2009, 8(4): 225-230. DOI: 10.3816/CCC.2009.n.038. [36] MADBOULY KM, HUSSEIN AM, ZEID A. Colorectal cancer surgery in portal hypertensive patients: does adjuvant oxaliplatin affect prognosis?[J]. Dis Colon Rectum, 2013, 56(5): 577-585. DOI: 10.1097/DCR.0b013e318286f8fc. [37] YAZAKI T, KAWASHIMA K, ISHIMURA N, et al. Oxaliplatin-related portal hypertension complicated with esophageal varices and refractory massive ascites[J]. Intern Med, 2022, 61(21): 3225-3231. DOI: 10.2169/internalmedicine.9266-21. [38] FUENTES-LACOUTURE MC, BARRERA-GARAVITO EC, GOMEZ A, et al. Non-cirrhotic portal hypertension in a patient with colonic carcinoma treated with oxaliplatin[J]. J Med Cases, 2021, 12(3): 99-101. DOI: 10.14740/jmc3630. [39] MORIOKA D, IZUMISAWA Y, YAMAGUCHI K, et al. Surgical intervention for portal hypertension caused by oxaliplatin-based chemotherapy: a case report and a review of literature regarding radiological and/or surgical interventions for oxaliplatin-associated portal hypertension[J]. Clin J Gastroenterol, 2020, 13(5): 799-805. DOI: 10.1007/s12328-020-01157-w. [40] HUANG X, LI F, WANG L, et al. Endoscopic treatment of gastroesophageal variceal bleeding after oxaliplatin-based chemotherapy in patients with colorectal cancer[J]. Endoscopy, 2020, 52(9): 727-735. DOI: 10.1055/a-1157-8611. -
本文二维码
计量
- 文章访问数: 434
- HTML全文浏览量: 93
- PDF下载量: 121
- 被引次数: 0
下载:
