Effect of cold ischemia time on early graft function and acute rejection after liver transplantation
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摘要:
目的 探讨不同冷缺血时间(CIT)对肝移植术后早期移植物功能和急性排斥反应(AR)的影响。 方法 收集并分析218例肝移植供、受者的临床资料, 按照供肝CIT分为A组(CIT≤6 h, 60例)、B组(6 h < CIT≤10 h, 89例)、C组(CIT > 10 h, 69例)3组。收集受者术后1、7、14 d的血液样本, 检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、CD4+T细胞三磷酸腺苷(ATP)的变化情况。分析术后各组受者的AR发生率和C4d沉积阳性率。 结果 各组ALT、AST和LDH水平在术后1 d即达到峰值, 随后逐渐下降, 至14 d各组各指标相当, 且术后时间与组别均存在交互效应。肝移植术后各组CD4+T细胞ATP水平逐渐上升, 至术后7 d达到峰值, 然后逐渐下降, 且术后时间与组别均存在交互效应。A、B、C 3组AR发生率分别为10%、12%、28%;与C组比较, A、B组的AR发生率明显降低(均为P < 0.05/3)。A、B、C组AR受者的C4d沉积阳性率分别为1/3、45%、89%;与C组比较, A组的C4d沉积阳性率明显降低(P=0.015)。 结论 CIT延长有可能导致肝移植术后早期肝功能损伤加重, 更易诱发体液性AR。 -
关键词:
- 冷缺血时间 /
- 肝移植 /
- 急性排斥反应 /
- 体液性排斥反应 /
- 三磷酸腺苷(ATP) /
- 丙氨酸转氨酶(ALT) /
- 天冬氨酸转氨酶(AST) /
- 乳酸脱氢酶(LDH) /
- 缺血-再灌注损伤
Abstract:Objective To evaluate the effect of different cold ischemia time (CIT) on early graft function and acute rejection (AR) after liver transplantation. Methods Clinical data of 218 donors and recipients undergoing liver transplantation were collected and analyzed. All patients were divided into three groups according to the CIT of donor liver: group A (CIT≤6 h, n=60), group B (6 h < CIT≤10 h, n=89) and group C (CIT > 10 h, n=69). Blood samples were collected on the 1, 7 and 14 d after liver transplantation. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and adenosine triphosphate (ATP) in CD4+T cells were detected. The incidence of AR and the positive rate of C4d deposition were analyzed. Results The ALT, AST and LDH levels in each group reached the peak on the 1 d after operation, and then gradually decreased. The indexes in each group were almost equivalent on the 14 d. An interaction effect existed between postoperative time and group. After liver transplantation, ATP levels in CD4+T cells were gradually increased in each group, peaked at postoperative 7 d, and then decreased gradually. An interaction effect was noted between postoperative time and group. The incidence of AR in groups A, B and C was 10%, 12% and 28%. Compared with group C, the incidence of AR in groups A and B was decreased significantly (both P < 0.05/3). The positive rate of C4d deposition in AR recipients of groups A, B and C was 1/3, 45% and 89% respectively. Compared with group C, the positive rate of C4d deposition in group A was decreased significantly (P=0.015). Conclusions The prolongation of CIT may lead to aggravation of early-stage liver function injury after liver transplantation, which is more easily to induce humoral AR. -
表 1 3组受者术后肝功能比较
Table 1. Comparison of postoperative liver function of recipients among 3 groups [M(Q), U/L]
组别 n AST ALT LDH 术后1 d 术后7 d 术后14 d 术后1 d 术后7 d 术后14 d 术后1 d 术后7 d 术后14 d A组 60 158(168) 51(63)c 42(16)c 173(241) 68(57)c 45(24)c 750(914) 608(353)c 279(113)c B组 89 307(229) 51(42)c 50(28)c 328(210) 70(34)c 50(29)c 847(888) 643(377)c 313(147)c C组 69 624(609)a, b 62(181)a, b, c 33(28)c 542(452)a, b 83(179)a, b, c 44(50)c 928(1 404)a 731(340)a, b, c 320(112)c H值 88.430 4.470 12.256 70.381 14.986 2.657 9.548 17.134 4.325 P值 < 0.001 0.107 0.002 < 0.001 0.001 0.265 0.008 < 0.001 0.115 注:与A组比较, aP < 0.05/3;与B组比较, bP < 0.05/3;与术后1 d比较, cP < 0.05/2。 表 2 3组受者术后CD4+T细胞ATP水平的比较
Table 2. Comparison of postoperative ATP levels of CD4+T cell in recipients among 3 groups[M(Q), μg/L]
组别 n 术后1 d 术后7 d 术后14 d A组 60 178(80) 222(94)c 203(52) B组 89 254(103)a 302(119)a, c 204(40)c C组 69 332(175)a, b 401(268)a, b, c 204(65)c H值 74.138 69.391 1.240 P值 < 0.001 < 0.001 0.538 注:与A组比较, aP < 0.05/3;与B组比较, bP < 0.05/3;与术后1 d比较, cP < 0.05/2。 -
[1] 中国肝移植注册中心, 国家肝脏移植医疗质量控制中心. 2018中国肝脏移植医疗质量报告[M].中国肝移植注册中心, 2018. [2] 谢秀华, 孔心涓, 饶伟.肝移植术后感染并发症的研究现状及进展[J/CD].实用器官移植电子杂志, 2017, 5(1): 61-64. DOI: 10.3969/j.issn.2095-5332.2017.01.018.XIE XH, KONG XJ, RAO W. The current status and process of infection complications after liver transplantation[J/CD]. Pract J Organ Transplant (Electr Vers), 2017, 5(1): 61-64. DOI: 10.3969/j.issn.2095-5332.2017.01.018. [3] ZHANG J, REN H, SUN Y, et al. Outcomes of adult liver transplantation from donation after brain death followed by circulatory death in China[J]. Ann Transplant, 2018, 23:285-291. DOI: 10.12659/AOT.907790. [4] PATERNO F, GUARRERA JV, WIMA K, et al. Clinical implications of donor warm and cold ischemia time in donor after circulatory death liver transplantation[J]. Liver Transpl, 2019, 25(9):1342-1352. DOI: 10.1002/lt.25453. [5] 中华医学会器官移植学分会.器官移植病理学临床技术操作规范(2019版)——肝移植[J].器官移植, 2019, 10(3):267-277.DOI:10.3969/j.issn.1674-7445.2019.03.008.Branch of Organ Transplantation of Chinese Medical Association. Clinical technical operation specification for pathology of organ transplantation (2019 edition): liver transplantation[J]. Organ Transplant, 2019, 10(3):267-277. DOI: 10.3969/j.issn.2095-5332.2017.01.018. [6] 董家勇, 李瑞东, 宋少华, 等.CD4+T淋巴细胞内ATP含量与肝癌肝移植术后肿瘤复发的关系[J].器官移植, 2010, 1(4):208-210, 215.DOI: 10.3969/j.issn.1674-7445.2010.04.004.DONG JY, LI RD, SONG SH, et al. Relationship between the ATP level in CD4+ T lymphocyte and recurrence of hepatocellular carcinoma after liver transplantation[J]. Organ Tranplant, 2010, 1(4):208-210, 215. DOI: 10.3969/j.issn.1674-7445.2010.04.004. [7] 杨扬, 邓宜南.抗体免疫诱导治疗在肝移植中的应用[J].临床肝胆病杂志, 2015, 31(12):2031-2034. DOI: 10.3969/j.issn.1001-5256.2015.12.010.YANG Y, DENG YN. Application of immune induction therapy with antibodies in liver tranplantation[J]. J Clin Hepatol, 2015, 31(12):2031-2034. DOI: 10.3969/j.issn.1001-5256.2015.12.010. [8] MIKHALSKI D, WISSING KM, GHISDAL L, et al. Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era ofimmunosuppression[J]. Transplantation, 2008, 85(7 Suppl):S3-S9. DOI: 10.1097/TP.0b013e318169c29e. [9] LOZANOVSKI VJ, KHAJEH E, FONOUNI H, et al. The impact of major extended donor criteria on graft failure and patient mortality after liver transplantation[J]. Langenbecks Arch Surg, 2018, 403(6):719-731. DOI: 10.1007/s00423-018-1704-z. [10] 邵文雨, 黄新立, 周浩明, 等.公民器官捐献供体质量对肝移植术后受体生存率的影响及其感染高危因素分析[J].临床外科杂志, 2018, 26(12):913-917. DOI: 10.3969/j.issn.1005-6483.2018.12.007.SHAO WY, HUANG XL, ZHOU HM, et al. Effect of donation after cardiac death donor qualty on receptor survival rate after liver transplantation and analysis of risk factors of infection[J]. J Clin Surg, 2018, 26(12):913-917. DOI: 10.3969/j.issn.1005-6483.2018.12.007. [11] JAY C, LADNER D, WANG E, et al. A comprehensive risk assessment of mortality following donation after cardiac death liver transplant - an analysis of the national registry[J]. J Hepatol, 2011, 55(4):808-813. DOI: 10.1016/j.jhep.2011.01.040. [12] HONG JC, YERSIZ H, KOSITAMONGKOL P, et al. Liver transplantation using organ donation after cardiac death: a clinical predictive index for graft failure-free survival[J]. Arch Surg, 2011, 146(9):1017-1023. DOI: 10.1001/archsurg.2011.240. [13] MATHUR AK, HEIMBACH J, STEFFICK DE, et al. Donation after cardiac death liver transplantation: predictors of outcome[J]. Am J Transplant, 2010, 10(11):2512-2519. DOI: 10.1111/j.1600-6143.2010.03293.x. [14] 中国医师协会器官移植医师分会, 中华医学会外科学分会器官移植学组, 中国肝移植注册中心科学委员会.中国移植器官保护专家共识(2016版)[J].器官移植, 2016, 7(5):339-350.DOI: 10.3969/j.issn.1674-7445.2016.05.003.Branch of Organ Transplant Physician of Chinese Medical Doctor Association, Division of Transplantation of Branch of Surgery of Chinese Medical Association, China Liver Transplant Registry (CLTR) Center Scientific Committee. Chinese expert consensus on the organ protection of transplantation (2016 edition)[J].Organ Transplant, 2016, 7(5):339-350. DOI:10.3969/j.issn. 1674-7445.2016.05.003. [15] 黑子清.肝移植围术期器官损伤机制及器官保护策略研究进展[J].中山大学学报(医学科学版), 2019, 40(4):487-492.HEI ZQ. Advances in mechanisms of perioperative organ injury and organ protective strategies of liver transplantation[J]. J Sun Yat-sen Univ (Med Sci), 2019, 40(4):487-492. [16] 唐晖, 傅斌生, 陈规划.心脏死亡器官捐献肝移植的供体功能维护[J].器官移植, 2016, 7(1):21-25. DOI: 10.3969/j.issn.1674-7445.2016.01.004.TANG H, FU BS, CHEN GH. Donor function maintenance of liver transplantation from donation after cardiac death[J]. Organ Transplant, 2016, 7(1):21-25. DOI: 10.3969/j.issn.1674-7445.2016.01.004. [17] WANG Y, WU J, JIANG B, et al. Relationship between ischemia/reperfusion injury and acute rejection of allogeneic liver transplant in rats[J]. Transplant Proc, 2014, 46(1):50-55. DOI: 10.1016/j.transproceed.2013.06.019. [18] 中国医院协会器官获取与分配管理工作委员会, 中国医师协会移植器官质量控制专业委员会.供体肝脏的质量控制标准(草案)[J].武汉大学学报(医学版), 2017, 38(6):954-960.Organ Acquisition and Distribution Management Working Comittee of China Hospital Association, Professional Committee for Quality Control of Transplant Organs of Chinese Medical Doctor Association. Standard of quality control of donor liver(draft)[J]. Med J Wuhan Univ, 2017, 38(6):954-960. [19] KOO J, WANG HL. Acute, chronic, and humoral rejection: pathologic features under current immunosuppressive regimes[J]. Surg Pathol Clin, 2018, 11(2):431-452. DOI: 10.1016/j.path.2018.02.011. [20] DONG JY, YIN H, LI RD, et al. The relationship between adenosine triphosphate within CD4(+) T lymphocytes and acute rejection after liver transplantation[J]. Clin Transplant, 2011, 25(3):E292-E296. DOI: 10.1111/j.1399-0012.2011.01429.x. [21] NEIL DAH, BELLAMY CO, SMITH M, et al. Global quality assessment of liver allograft C4d staining during acute antibody-mediated rejection in formalin-fixed, paraffin-embedded tissue[J]. Hum Pathol, 2018, 73:144-155. DOI: 10.1016/j.humpath.2017.12.007. [22] KOVANDOVA B, SLAVCEV A, SEKERKOVA Z, et al. Antibody-mediated rejection after liver transplantation-relevance of C1q and C3d-binding antibodies[J]. HLA, 2018, 92 (Suppl 2):34-37. DOI: 10.1111/tan.13354. [23] DAO M, HABÈS D, TAUPIN JL, et al. Morphological characterization of chronic antibody-mediated rejection in ABO-identical or ABO-compatible pediatric liver graft recipients[J]. Liver Transpl, 2018, 24(7):897-907. DOI: 10.1002/lt.25187. [24] PARAJULI S, JOACHIM E, ALAGUSUNDARAMOORTHY S, et al. Donor-specific antibodies in the absence of rejection are not a risk factor for allograft failure[J]. Kidney Int Rep, 2019, 4(8):1057-1065. DOI: 10.1016/j.ekir.2019.04.011. [25] LEE M. Antibody-mediated rejection after liver transplant[J]. Gastroenterol Clin North Am, 2017, 46(2):297-309. DOI: 10.1016/j.gtc.2017.01.005.
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