胸腺法新在肝移植术后严重肺部感染患者中的应用研究

摘要: 目的探讨胸腺法新用于治疗肝移植术后严重肺部感染的疗效及安全性。方法 2008年1月至2014年5月在解放军第309医院全军器官移植研究所进行肝移植的患者中, 围手术期共发生严重肺部感染27例。按有否应用胸腺法新分为胸腺法新组(11例)与对照组(16例)。胸腺法新应用方案为1.6 mg皮下注射, 1次/日, 连续应用2周。对照组采用常规抗感染治疗。比较两组患者呼吸机应用时间、发热持续时间、入住重症监护室(ICU)时间、病死率等指标, 同时监测两组患者急性排斥反应(AR)发生情况。结果胸腺法新组呼吸机应用时间、发热持续时间、入住ICU时间均较对照组明显缩短(均为P < 0.05)。两组间病死率差异无统计学意义, 两组患者均未发生临床型AR。胸腺法新组未观察到与胸腺法新相关的不良反应。结论胸腺法新可以明显改善肝移植术后严重肺部感染患者抗感染疗效, 不增加AR发生率, 在肝移植肺部感染患者中应用是安全有效的。
- 肝移植 /
- 肺部感染 /
- 胸腺法新 /
- 急性排斥反应
Abstract: Objective To explore the efficacy and safety of thymalfasin in the treatment of severe pulmonary infection after liver transplantation. Methods Twenty seven patients who developed severe lung infection after undergoing liver transplantation in Organ Transplant Institute of the 309^th Hospital of People's Liberation Army from January 2008 to May 2014 were enrolled in this study. According to whether the application of thymalfasin, the patients were divide into thymalfasin group(n=11) and control group(n=16). In the thymalfasin group, thymalfasin was administered via subcutaneous injection at a dose of 1.6 mg once daily for consecutive two weeks. In the control group, conventional anti-infection therapy was delivered. Ventilator time, duration of fever, the length of intensive care unit(ICU) stay and mortality were statistically compared between two groups. And the incidence of acute rejection (AR) was monitored. Results Ventilator time, duration of fever, length of ICU stay of patients in the thymalfasin group were significantly shortened compared with those in the control group (all in P < 0.05). There was no significant difference in the mortality between two groups. No clinical AR was observed in either group. No thymalfasin-related adverse event was found in the thymalfasin group. Conclusions Thymalfasin can improve the curative effect to anti-infection of patients with severe pulmonary infection after liver transplantation without the incidence of AR, which is efficacious and safe in the treatment of severe pulmonary infection.
- Liver transplantation /
- Pulmonary infection /
- Thymalfasin /
- Acute rejection

HTML全文

表 1 两组患者发生严重肺部感染前的一般资料比较

Table 1. Comparison of patients' characteristics between two groups before severe pulmonary infection

组别	n	性别 (男/女，n/n)	年龄 (岁，x±s)	术前痰培养阳性病例数(n)	术前入住ICU 病例数(n)	术前肝功能评分 (分，x±s)	术中出血量 (ml，平均值)	手术时间 (h，x±s)
胸腺法新组	11	10/1	53±7	3	2	11.5±2.5	1 800	7.0±1.2
对照组	16	14/2	52±6	4	4	11.7±2.2	2 700	7.3±1.2
统计值		0.120	0.118	0.099	0.003	0.261	1.135	0.674
P值		0.729	0.907	0.753	0.958	0.797	0.246	0.507
注：肝功能评分为Child-Pugh评分

下载: 导出CSV

表 2 两组患者的临床观察指标比较

Table 2. Comparison of clinical observation indicators of the patients between two groups(x±s)

组别	n	呼吸机应用时间(h)	发热持续时间(d)	入住ICU 时间(d)
胸腺法新组	11	22±12	9±4	13±4
对照组	16	44±33	13±6	20±8
t值		2.452	2.123	2.810
P值		0.024	0.044	0.010

下载: 导出CSV

参考文献(18)

[1]	Feltracco P, Carollo C, Barbieri S, et al. Early respiratory complications after liver transplantation[J]. World J Gastroenterol, 2013, 19(48):9271-9281. doi: 10.3748/wjg.v19.i48.9271
[2]	Müller V, Kováts Z, Horváth G. Pulmonary infections following solid organ transplantation[J]. Orv Hetil, 2012, 153(23):899-903. doi: 10.1556/OH.2012.29395
[3]	Serafino A, Pierimarchi P, Pica F, et al. Thymosin α1 as a stimulatory agent of innate cell-mediated immune response[J]. Ann N Y Acad Sci, 2012(1270):13-20. http://www.researchgate.net/publication/232227940_Thymosin_1_as_a_stimulatory_agent_of_innate_cell-mediated_immune_response
[4]	Garaci E. Thymosin alpha1:a historical overview[J]. Ann N Y Acad Sci, 2007(1112):14-20. doi: 10.1196-annals.1415.039/
[5]	Roy R, Singh SM, Shanker A, et al. Mechanism of thymocyte apoptosis induced by serum of tumor-bearing host:the molecular events involved and their inhibition by thymosin alpha-1[J]. Int J Immunopharmacol, 2000, 22(4):309-321. doi: 10.1016/S0192-0561(99)00087-9
[6]	Vogler MA, Teppler H, Gelman R, et al. Daily low-dose subcutaneous interleukin-2 added to single-or dual-nucleoside therapy in HIV infection does not protect against CD4⁺ T-cell decline or improve other indices of immune function:results of a randomized controlled clinical trial (ACTG 248)[J]. J Acquir Immune Defic Syndr, 2004, 36(1):576-587. doi: 10.1097/00126334-200405010-00005
[7]	Nebbia G, Mattes FM, Sabin CA, et al. Differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation[J]. Transplantation, 2007, 84(5):605-610. doi: 10.1097/01.tp.0000280555.08651.11
[8]	Ciancio A, Rizzetto M. Thymalfasin in the treatment of hepatitis B and C[J]. Ann N Y Acad Sci, 2010(1194):141-146. https://www.researchgate.net/publication/44662013_Thymalfasin_in_the_treatment_of_hepatitis_B_and_C
[9]	Garaci E, Pica F, Serafino A, et al. Thymosin α1 and cancer:action on immune effector and tumor target cells[J]. Ann N Y Acad Sci, 2012(1269):26-33. doi: 10.1111/j.1749-6632.2012.06697.x/references
[10]	Morton B, Pennington SH, Gordon SB. Immunomodulatory adjuvant therapy in severe community-acquired pneumonia[J]. Expert Rev Respir Med, 2014, 8(5):587-596. doi: 10.1586/17476348.2014.927736
[11]	Song EY, Shin Y, Roh EY, et al. Serum HBsAg levels during peginterferon alpha-2a treatment with or without thymosin alpha-1 in HBeAg-positive chronic hepatitis B patients[J]. J Med Virol, 2011, 83(1):88-94. doi: 10.1002/jmv.v83:1
[12]	Sherman KE. Thymosin alpha 1 for treatment of hepatitis C virus:promise and proof[J]. Ann N Y Acad Sci, 2010(1194):136-140. https://www.researchgate.net/publication/44662012_Thymosin_a_1_for_treatment_of_hepatitis_C_virus_Promise_and_proof
[13]	刘洪涛, 彭龙开, 谢续标, 等.胸腺肽a1联合抗病毒药治疗肾移植术后巨细胞病毒肺炎[J].中国现代医学杂志, 2007, 17(22):2784-2786. http://d.wanfangdata.com.cn/Periodical/zgxdyxzz200722028 Liu HT, Peng LK, Xie XB, et al. Combination therapy of thymosinal and antiviral drugs in kidney transplant recipients with cytomegalovirus pneumonia[J]. Chin J Mod Med, 2007, 17(22):2784-2786. http://d.wanfangdata.com.cn/Periodical/zgxdyxzz200722028
[14]	傅英梅, 徐战平.胸腺肽在肾移植术后巨细胞病毒肺炎治疗作用初探[J].国际医药卫生导报, 2005, 11(8):10-11. http://d.wanfangdata.com.cn/Periodical/gjyywsdb200508004 Fu YM, Xu ZP. A preliminary study on thymosin in treatment of cytomegalovirus pneumonia after renal transplantation[J]. Int Med Health Guid News, 2005, 11(8):10-11. http://d.wanfangdata.com.cn/Periodical/gjyywsdb200508004
[15]	Ding JH, Wang LL, Chen Z, et al. The role of Tα1 on the infective patients after hematopoietic stem cell transplantation[J]. Int J Hematol, 2013, 97(2):280-283. doi: 10.1007/s12185-012-1208-5
[16]	Zhang P, Chan J, Dragoi AM, et al. Activation of IKK by thymosin alpha1 requires the TRAF6 signalling pathway[J]. J EMBO Rep, 2005, 6(6):531-537. doi: 10.1038/sj.embor.7400433
[17]	Grottesi A, Sette M, Palamara T, et al. The conformation of peptide thymosin alpha 1 in solution and in a membrane-like environment by circular dichroism and NMR spectroscopy. a possible model for its interaction with the lymphocyte membrane[J]. J Peptides, 1998, 19(10):1731-1738. doi: 10.1016/S0196-9781(98)00132-6
[18]	Hwang S, Kim KH, Song GW, et al. Peritransplant monitoring of immune cell function in adult living donor liver transplantation[J]. Transplant Proc, 2010, 42(7):2567-2571. doi: 10.1016/j.transproceed.2010.04.040