肝细胞癌治疗方式对门静脉压力的影响

陈博文; 程家敏; 张林枝; 雷进; 高小强; 陆荫英

doi:10.3969/j.issn.1001-5256.2022.07.038

肝细胞癌治疗方式对门静脉压力的影响

DOI: 10.3969/j.issn.1001-5256.2022.07.038

陈博文^{1, 2},
程家敏²,
张林枝^{2, 3},
雷进^{2, 4},
高小强^{2, 4},
陆荫英^{1, 2, 5, , ,}

1.
北京大学三〇二临床医学院，北京 100039
2.
中国人民解放军总医院第五医学中心肝病医学部，北京 100039
3.
天津医科大学肿瘤医院，天津 300060
4.
贵州医科大学临床医学院，贵阳 550004
5.
深圳大学生命与海洋科学学院，广东省表观遗传学重点实验室，深圳 518055

基金项目:

深圳市科技创新委员会可持续发展专项 (KCXFZ202002011006448)

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：陈博文负责文献调研、论文撰写; 程家敏负责拟定撰写思路; 张林枝、雷进、高小强负责修改完善论文; 陆荫英负责指导文章写作并最终定稿。

详细信息

通信作者:
陆荫英，luyinying1973@163.com

计量
- 文章访问数: 535
- HTML全文浏览量: 122
- PDF下载量: 62
- 被引次数: 0
出版历程
- 收稿日期: 2021-12-13
- 录用日期: 2022-01-27
- 出版日期: 2022-07-20

Effect of the treatment modality for hepatocellular carcinoma on portal venous pressure

Bowen CHEN^{1, 2},
Jiamin CHENG²,
Linzhi ZHANG^{2, 3},
Jin LEI^{2, 4},
Xiaoqiang GAO^{2, 4},
Yinying LU^{1, 2, 5
, ,
,}

1.
Peking University 302 Clinical Medical School, Beijing 100039, China
2.
Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
3.
Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
4.
Guizhou Medical University Clinical Medical School, Guiyang 550004, China
5.
Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, China

Research funding:

Special Program of Sustainable Development Issued by the Science, Technology and Innovation Commission of Shenzhen Municipality (KCXFZ202002011006448)

More Information

Corresponding author: LU Yinying, luyinying1973@163.com(ORCID: 0000-0002-7737-2334)

摘要

摘要: 肝硬化基础上发生的门静脉高压是肝细胞癌常见的合并症，也是影响治疗决策及生存预后的关键因素。肝细胞癌的不同治疗方式也会对门静脉压力起着不同的影响。既往文献显示，肝切除术、反复肝动脉化疗栓塞、奥沙利铂化疗、仑伐替尼治疗可导致门静脉压力升高，而索拉非尼、瑞戈非尼则在临床应用和/或动物实验中被证实在短期内发挥降低门静脉压力的作用。新型联合治疗方案，如阿替丽珠单抗联合贝伐珠单抗以及多纳非尼、阿帕替尼、安罗替尼等新上市的肝细胞癌一线或二线治疗靶向药物等对门静脉高压相关并发症如消化道出血等的影响在相关临床试验中也有报道，但对门静脉压力的整体影响尚待研究。
- 癌, 肝细胞 /
- 肿瘤治疗方案 /
- 门静脉压
Abstract: Portal hypertension (PH) on the basis of liver cirrhosis is a common complication of hepatocellular carcinoma (HCC), and it is also a key factor affecting treatment decisions and prognosis. Different treatment modalities for HCC may have different effects on portal venous pressure. Through a literature review, it is concluded that hepatectomy, repeated transcatheter arterial chemoembolization, oxaliplatin chemotherapy, and lenvatinib can lead to the increase in portal venous pressure, while sorafenib and regorafenib have been proved to reduce portal venous pressure within a short term in clinical trials and/or animal experiments. There are also reports on the effect of novel combination treatment regimens (such as atezolizumab combined with bevacizumab) and newly marketed first-line or second-line targeted drugs for HCC (such as donafenib, apatinib, and anlotinib) on portal hypertension-related complications including gastrointestinal bleeding in related clinical trials, but further studies are needed to investigate their overall effect on portal venous pressure.
- Carcinoma, Hepatocellular /
- Antineoplastic Protocols /
- Portal Pressure

HTML全文

参考文献(37)

[1]	ZHAO LH, JIA JD. Etiological diagnosis and standard treatment of portal hypertension should be taken seriously[J]. J Clin Hepatol, 2019, 35(1): 10-12. DOI: 10.3969/j.issn.1001-5256.2019.01.001. 赵连晖, 贾继东. 应重视门静脉高压症的病因诊断及规范治疗[J]. 临床肝胆病杂志, 2019, 35(1): 10-12. DOI: 10.3969/j.issn.1001-5256.2019.01.001.
[2]	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.
[3]	RIPOLL C, GROSZMANN RJ, GARCIA-TSAO G, et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis[J]. J Hepatol, 2009, 50(5): 923-928. DOI: 10.1016/j.jhep.2009.01.014.
[4]	ZHONG JH, KE Y, GONG WF, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma[J]. Ann Surg, 2014, 260(2): 329-340. DOI: 10.1097/SLA.0000000000000236.
[5]	REIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update[J]. J Hepatol, 2022, 76(3): 681-693. DOI: 10.1016/j.jhep.2021.11.018.
[6]	XU XF, XING H, HAN J, et al. Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China[J]. JAMA Surg, 2019, 154(3): 209-217. DOI: 10.1001/jamasurg.2018.4334.
[7]	GUO ZY, HONG Y. Advances in the throughout assessment and management of surgical resection for liver cancer and cirrhotic completed with portal hypertension[J]. J Clin Surg, 2021, 29(11): 1092-1095. DOI: 10.3969/j.issn.1005-6483.2021.11.028. 郭张有, 洪源. 肝硬化门静脉高压症肝癌手术切除全程评估和管理的进展[J]. 临床外科杂志, 2021, 29(11): 1092-1095. DOI: 10.3969/j.issn.1005-6483.2021.11.028.
[8]	BOGNER A, REISSFELDER C, STRIEBEL F, et al. Intraoperative increase of portal venous pressure is an immediate predictor of posthepatectomy liver failure after major hepatectomy: a prospective study[J]. Ann Surg, 2021, 274(1): e10, e17. DOI: 10.1097/SLA.0000000000003496.
[9]	LAN X, ZHANG H, LI H, et al. Dynamic changes of portal vein pressure gradient under different degrees of liver cirrhosis and resection volume in the first week post hepatectomy[J]. Hepatol Res, 2018, 48(12): 978-988. DOI: 10.1111/hepr.13197.
[10]	NI YB, ZHU JY. Resection of hepatocellular carcinoma with portal hypertension[J]. J Hepatobiliary Sur, 2017, 25(5): 321-322. DOI: 10.3969/j.issn.1006-4761.2017.05.001. 倪彦彬, 朱继业. 合并门静脉高压的肝癌切除术[J]. 肝胆外科杂志, 2017, 25(5): 321-322. DOI: 10.3969/j.issn.1006-4761.2017.05.001.
[11]	CARRAPITA JG, ROCHA C, DONATO H, et al. Portal venous pressure variation during hepatectomy: a prospective study[J]. Acta Med Port, 2019, 32(6): 420-426. DOI: 10.20344/amp.10892.
[12]	SHEN ZF, LIANG X. Current status of radical laparoscopy for treating hepatocellular carcinoma with portal hypertension[J]. World J Clin Cases, 2021, 9(11): 2419-2432. DOI: 10.12998/wjcc.v9.i11.2419.
[13]	LI XL, ZHU XD, XIAO N, et al. A prospective study of the effect of terlipressin on portal vein pressure and clinical outcomes after hepatectomy: A pilot study[J]. Surgery, 2020, 167(6): 926-932. DOI: 10.1016/j.surg.2020.01.013.
[14]	ABBAS MS, MOHAMED KS, IBRAHEIM OA, et al. Effects of terlipressin infusion on blood loss and transfusion needs during liver resection: A randomised trial[J]. Acta Anaesthesiol Scand, 2019, 63(1): 34-39. DOI: 10.1111/aas.13226.
[15]	VILLANUEVA A. Hepatocellular Carcinoma[J]. N Engl J Med, 2019, 380(15): 1450-1462. DOI: 10.1056/NEJMra1713263.
[16]	YANG W, YAN K, GOLDBERG SN, et al. Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment[J]. World J Gastroenterol, 2016, 22(10): 2993-3005. DOI: 10.3748/wjg.v22.i10.2993.
[17]	LEE S, JEONG WK, RHIM H. Repeated percutaneous radiofrequency ablation for hepatocellular carcinoma in patients with cirrhosis: assessment of safety based on liver function and portal hypertension parameters[J]. J Vasc Interv Radiol, 2014, 25(10): 1573-1579. DOI: 10.1016/j.jvir.2014.06.015.
[18]	KHISTI R, PATIDAR Y, GARG L, et al. Correlation of baseline portal pressure (hepatic venous pressure gradient) and indocyanine green clearance test with post-transarterial chemoembolization acute hepatic failure[J]. J Clin Exp Hepatol, 2019, 9(4): 447-452. DOI: 10.1016/j.jceh.2018.09.004.
[19]	SCHEINER B, ULBRICH G, MANDORFER M, et al. Short- and long-term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma[J]. United European Gastroenterol J, 2019, 7(6): 850-858. DOI: 10.1177/2050640619840199.
[20]	LIU K, MIN XL, PENG J, et al. The changes of HIF-1α and VEGF expression after TACE in patients with hepatocellular carcinoma[J]. J Clin Med Res, 2016, 8(4): 297-302. DOI: 10.14740/jocmr2496w.
[21]	PUENTE A, FORTEA JI, DEL POZO C, et al. Porto-sinusoidal vascular disease associated to oxaliplatin: an entity to think about It[J]. Cells, 2019, 8(12): 1506. DOI: 10.3390/cells8121506.
[22]	KATAMURA Y, AIKATA H, TAKAKI S, et al. Intra-arterial 5-fluorouracil/interferon combination therapy for advanced hepatocellular carcinoma with or without three-dimensional conformal radiotherapy for portal vein tumor thrombosis[J]. J Gastroenterol, 2009, 44(5): 492-502. DOI: 10.1007/s00535-009-0033-y.
[23]	DA FONSECA LG, REIG M, BRUIX J. Tyrosine kinase inhibitors and hepatocellular carcinoma[J]. Clin Liver Dis, 2020, 24(4): 719-737. DOI: 10.1016/j.cld.2020.07.012.
[24]	LLOVET JM, KELLEY RK, VILLANUEVA A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7(1): 6. DOI: 10.1038/s41572-020-00240-3.
[25]	WEI L, WAN H. Roles of hemodynamic alterations in portal hypertension and cirrhosis[J]. J Clin Hepatol, 2013, 29(4): 308-310. DOI: 10.3969/j.issn.1001-5256.2013.04.019. 魏丽, 万红. 门静脉高压症血流动力学改变的发病机理[J]. 临床肝胆病杂志, 2013, 29(4): 308-310. DOI: 10.3969/j.issn.1001-5256.2013.04.019.
[26]	ZHU Y, CHENG Y, LI AM, et al. Therapeutic effect of sorafeinib on portal hypertension: research progress and mechanisms[J]. J Southern 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.
[27]	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.
[28]	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.
[29]	KUDO M. Lenvatinib may drastically change the treatment landscape of hepatocellular carcinoma[J]. Liver Cancer, 2018, 7(1): 1-19. DOI: 10.1159/000487148.
[30]	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.
[31]	FINN RS, QIN S, IKEDA M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905. DOI: 10.1056/NEJMoa1915745.
[32]	General Office of National Health Commission. Standard for diagnosis and treatment of primary liver cancer (2022 edition)[J]. J Clin Hepatol, 2022, 38(2): 288-303. DOI: 10.3969/j.issn.1001-5256.2022.02.009. 国家卫生健康委办公厅. 原发性肝癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38(2): 288-303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.
[33]	XU J, SHEN J, GU S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): A Nonrandomized, open-label, phase Ⅱ trial[J]. Clin Cancer Res, 2021, 27(4): 1003-1011. DOI: 10.1158/1078-0432.CCR-20-2571.
[34]	LU W, JIN XL, YANG C, et al. Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial[J]. Cancer Biol Ther, 2017, 18(6): 433-438. DOI: 10.1080/15384047.2017.1323589.
[35]	MEI K, QIN S, CHEN Z, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/Ⅱ trial[J]. J Immunother Cancer, 2021, 9(3): e002191. DOI: 10.1136/jitc-2020-002191.
[36]	SUN Y, ZHOU A, ZHANG W, et al. Anlotinib in the treatment of advanced hepatocellular carcinoma: an open-label phase Ⅱ study (ALTER-0802 study)[J]. Hepatol Int, 2021, 15(3): 621-629. DOI: 10.1007/s12072-021-10171-0.
[37]	SHIN SW, AHN KS, KIM SW, et al. Liver resection versus local ablation therapies for hepatocellular carcinoma within the milan criteria: a systematic review and meta-analysis[J]. Ann Surg, 2021, 273(4): 656-666. DOI: 10.1097/SLA.0000000000004350.