肝癌肝移植术后预防复发的全程管理探讨

摘要/Abstract

摘要： 肝移植是治疗肝细胞癌（hepatocellular carcinoma,HCC）的重要措施之一,尤其是对于合并终末期肝病的患者。但移植术后的肿瘤复发,严重制约了患者的长期生存。因此,如何预防移植术后HCC复发是提高HCC肝移植远期疗效的关键。本文从围手术期的治疗全流程管理的角度,就预防HCC肝移植患者术后复发展开阐述,并从手术、用药等多维度综述相关临床进展。

关键词: 肝细胞癌, 肝移植, 预防, 复发, 免疫抑制

Abstract: Liver transplantation is one of the important measures for the treatment of hepatocellular carcinoma, especially for patients with end-stage liver disease. However, tumor recurrence after transplantation severely restricts the patient's long-term survival. Therefore, how to prevent the recurrence of liver cancer after transplantation is the key to improve the long-term efficacy of liver transplantation for liver cancer. This article discusses the prevention of postoperative recurrence of liver cancer patients after liver transplantation from the perspective of perioperative management of the entire treatment process, and reviews relevant clinical progress from multiple dimensions such as surgery and medication.

Key words: Hepatocellular carcinoma, Liver transplantation, Prevention, Recurrence, Immunosuppression

郑元文, 刘军. 肝癌肝移植术后预防复发的全程管理探讨[J]. 肝癌电子杂志, 2021, 8(3): 46-50.

Zheng Yuanwen, Liu Jun. Discussion on the whole course management of preventing recurrence of liver cancer after liver transplantation[J]. Electronic Journal of Liver Tumor, 2021, 8(3): 46-50.

参考文献

[1] DE'ANGELIS N, LANDI F, CARRA M C, et al. Managements of recurrent hepatocellular carcinoma after liver transplantation: A systematic review[J]. World J Gastroenterol, 2015, 21(39): 11185-11198.
[2] XU X, LU D, LING Q, et al.Liver transplantation for hepatocellular carcinoma beyond the Milan criteria[J]. Gut, 2016, 65(6): 1035.
[3] 郎韧,吕少诚.原发性肝癌肝脏移植术适应标准的发展现状与展望[J].肝癌电子杂志,2018,5(4):8-12.
[4] 彭志海,孙红成. 肝移植术后肝癌复发[J]. 中华消化外科杂志, 2016,1(5):444-447 .
[5] GIUSEPPE T, PAOLO M, ROBERTO B, et al.Oncological Impact of M-Tor Inhibitor Immunosuppressive Therapy after Liver Transplantation for Hepatocellular Carcinoma: Review of the Literature[J]. Front Pharmacol, 2016, 7: 387.
[6] BODZIN A S, LUNSFORD K E, MARKOVIC D, et al.Predicting Mortality in Patients Developing Recurrent Hepatocellular Carcinoma After Liver Transplantation[J]. Ann Surg, 2017, 266(1): 118-125.
[7] VAGEFI P A, DODGE J L, YAO F Y, et al.The Potential Role of the Donor in Hepatocellular Carcinoma Recurrence Following Liver Transplantation[J]. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2015, 21(2): 187.
[8] POMPILI M, FRANCICA G, PONZIANI F R, et al.Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation[J]. World J Gastroenterol, 2013, 19(43): 7515-7530.
[9] KOCABAYOGLU P, PIRAS-STRAUB K, GERKEN G, et al.Expression of Fibrogenic Markers in Tumor and Tumor-Surrounding Tissue at Time of Transplantation Correlates with Recurrence of Hepatocellular Carcinoma in Patients Undergoing Liver Transplantation[J]. Ann Transplant, 2017, 22: 446-454.
[10] FERNANDEZ-SEVILLA E, ALLARD MA, SELTEN J, et al. Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection? [J]. Liver Transpl.2017 Apr; 23(4): 440-447.
[11] AGOPIAN VG, HARLANDER-LOCKE MP, RUIZ RM, et al.Impact of pretransplant bridging locoregional therapy for patients with hepatocellular carcinoma within Milan criteria undergoing liver transplantation: Analysis of 3601 patients from the US multicenter HCC transplant consortium[J]. Ann Surg, 2017, 266: 525-535.
[12] KULIK L, HEIMBACH JK, ZAIEM F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis[J]. Hepatology, 2018 Jan; 67(1): 381-400.
[13] MEHTA N, YAO FY.Living donor liver transplantation for hepatocellular carcinoma: To expand (beyond Milan) or downstage (to Milan)?[J]. Liver Transpl, 2018, 24(3): 327-329.
[14] LLOVET JM, PAVEL M, RIMOLA J, et al.Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria (Barcelona Clinic Liver Cancer extended criteria)[J]. Liver Transpl, 2018, 24(3): 369-379.
[15] KARDASHIAN A, FLORMAN SS, HAYDEL B, et al.Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria[J]. Hepatology, 2020, 72(6): 2014-2028.
[16] GU XQ, ZHENG WP, TENG DH, et al.Impact of non-oncological factors on tumor recurrence after liver transplantation in hepatocellular carcinoma patients[J]. World J Gastroenterol, 2016, 22(9): 2749-2759.
[17] MAN K, SHIH KC, NG KT, et al.Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts[J]. Ann Surg, 2010, 251(6): 1154-1161.
[18] CHENG JW, SHI YH, FAN J, et al.An immune function assay predicts post-transplant recurrence in patients with hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2011, 137(10): 1445-1453.
[19] CHEN K, MAN K, METSELAAR HJ, et al.Rationale of personalized immunosuppressive medication for hepatocellular carcinoma patients after liver transplantation[J]. Liver Transpl, 2014, 20(3): 261-269.
[20] ANGELICO R, PARENTE A, MANZIA TM.Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?[J]. Transl Gastroenterol Hepatol, 2017, 21(2): 74.
[21] 中国医师协会器官移植医师分会,中华医学会器官移植学分会.中国肝癌肝移植临床实践指南(2018版)[J].肝癌电子杂志,2018,5(4): 1-7.
[22] WEI Q, GAO F, ZHUANG R, et al.A national report from China Liver Transplant Registry: steroid avoidance after liver transplantation for hepatocellular carcinoma[J]. Chin J Cancer Res, 2017, 29(5): 426-437.
[23] LERUT J, IESARI S, FOGUENNE M, et al.Hepatocellular cancer and recurrence after liver transplantation: what about the impact of immunosuppression?[J]. Transl Gastroenterol Hepatol, 2017, 2(10): 80.
[24] GEISSLER EK, SCHNITZBAUER AA, ZÜLKE C, et al. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Transplantation[J]. 2016, 100(1): 116-125.
[25] CHOLONGITAS E, MAMOU C, RODRÍGUEZ-CASTRO KI, et al. Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review[J]. Transpl Int, 2014, 27(10): 1039-1049.
[26] TOSO C, MERANI S, BIGAM DL, et al.Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma[J]. Hepatology, 2010, 51(4): 1237-1243.
[27] GRIGG SE, SARRI GL, GOW PJ, et a. Systematic review with meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma[J]. Aliment Pharmacol Ther. 2019, 49(10): 1260-1273.
[28] CHOLONGITAS E, ANTONIADIS N, GOULIS I, et al.Trough Levels of Everolimus Are Associated With Recurrence Rates of Hepatocellular Carcinoma After Liver Transplantation[J]. Transplant Proc, 2019, 51(2): 450-453.
[29] JENG LB, LEE SG, SOIN AS, et al.Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study[J]. Am J Transplant, 2018, 18(6): 1435-1446.
[30] RODRÍGUEZ-PERÁLVAREZ M, GUERRERO M, BARRERA L, et al. Impact of Early Initiated Everolimus on the Recurrence of Hepatocellular Carcinoma After Liver Transplantation. Transplantation[J]. 2018, 102(12): 2056-2064.
[31] SAAB S, MCTIGUE M, FINN RS, et al.Sorafenib as adjuvant therapy for high-risk hepatocellular carcinoma in liver transplant recipients: feasibility and efficacy[J]. Exp Clin Transplant, 2010, 8(4): 307-313.
[32] TENG CL, HWANG WL, CHEN YJ, et al. Sorafenib for hepatocellular carcinoma patients beyond Milan criteria after orthotopic liver transplantation: a case control study[J]. World J Surg Oncol, 2012, 17; 10: 41.
[33] EILARD MS, ANDERSSON M, NAREDI P, et al.A prospective clinical trial on sorafenib treatment of hepatocellular carcinoma before liver transplantation[J]. BMC Cancer, 2019, 19(1): 568.
[34] JUNG DH, TAK E, HWANG S, et al.Antitumor effect of sorafenib and mammalian target of rapamycin inhibitor in liver transplantation recipients with hepatocellular carcinoma recurrence[J]. Liver Transpl, 2018, 24(7): 932-945.
[35] SATAPATHY SK, DAS K, KOCAK M, et al.No apparent benefit of preemptive sorafenib therapy in livertransplant recipients with advanced hepatocellular carcinoma on explant[J]. Clin Transplant,2018, 32(5): e13246.
[36] OLTHOFF KM, ROSOVE MH, SHACKLETON CR, et al.Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma[J]. Ann Surg, 1995,221(6): 734-743.
[37] ZHANG Q, CHEN H, LI Q, et al.Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study[J]. Invest New Drugs, 2011, 29(6): 1360-1369.
[38] XU J, SHEN ZY, CHEN XG, et al.A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation[J]. Hepatology, 2007, 45(2): 269-276.
[39] SÖDERDAHL G, BÄCKMAN L, ISONIEMI H, et al. A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma[J]. Transpl Int, 2006, 19(4): 288-294.
[40] LIPSON EJ, BAGNASCO SM, MOORE J JR, et al.Tumor regression and allograft rejection after administration of anti-PD-1[J]. N Engl J Med, 2016, 374(9): 896-898.
[41] 汪国营,唐晖,张英才,等.程序性死亡受体(PD)-1单克隆抗体治疗肝癌肝移植术后复发诱发急性免疫性肝炎:附1例报告[J].器官移植,2016,7(1):44-47.
[42] FISHER J, ZEITOUNI N, FAN W, . Immune checkpoint inhibitor therapy in solid organ transplant recipients: A patient-centered systematic review[J]. J Am Acad Dermatol, 2020, 82(6): 1490-1500.
[43] DE BRUYN P, VAN GESTEL D, OST P, et al.Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?[J]. Curr Opin Oncol, 2019, 31(2): 54-64.
[44] QU LS, LIU JX, ZHU J, et al.Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load[J]. Ann Hepatol, 2017, 16(3): 412-420.
[45] EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER.EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398.
[46] FUNG J, WONG T, CHOK K, et al.Long-term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years[J]. Hepatology, 2017, 66(4): 1036-1044.
[47] KIM JM, JOH JW, KIM SJ, et al.Steroid withdrawal in adult liver transplantation: occurrence at a single center[J]. Transplant Proc, 2010, 42(10): 4132-4136.
[48] LO CM, LAU GK, CHAN SC, et al.Efficacy of a pre-S containing vaccine in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B[J]. Am J Transplant, 2007, 7(2): 434-439.
[49] YOUNOSSI ZM, STEPANOVA M, CHARLTON M, et al.Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial[J]. Lancet Gastroenterol Hepatol, 2016, 1(2): 122-132.
[50] LEVITSKY J, VERNA EC, O'LEARY JG, et al. Perioperative Ledipasvir-Sofosbuvir for HCV in Liver-Transplant Recipients[J]. N Engl J Med, 2016, 375(21): 2106-2108.