肝移植术后他克莫司导致双下肢疼痛综合征的治疗经验

郑永根; 周林; 杜国盛; 朱志东; 封立魁

doi:10.3969/j.issn.1674-7445.2019.04.017

肝移植术后他克莫司导致双下肢疼痛综合征的治疗经验

doi: 10.3969/j.issn.1674-7445.2019.04.017

100091 北京，中国人民解放军医学院（郑永根）；中国人民解放军总医院第八医学中心肝胆外科（周林、杜国盛、朱志东、封立魁）

基金项目:

国家自然科学基金 81771717

详细信息

作者简介:
郑永根，男，1987年生，硕士，医师，研究方向为肝胆外科，Email：nishizhen135@163.com

通讯作者:
杜国盛，男，1964年生，博士，主任医师，研究方向为肝胆外科，Email：duguosheng309@126.com

中图分类号: R617
计量
- 文章访问数: 305
- HTML全文浏览量: 254
- PDF下载量: 9
- 被引次数: 0
出版历程
- 收稿日期: 2019-04-03
- 网络出版日期: 2021-01-19
- 刊出日期: 2019-07-15

Therapeutic experience of tacrolimus-induced pain syndrome of bilateral lower limbs after liver transplantation

Medical School of Chinese People's Liberation Army, Beijing 100091, China

More Information

Corresponding author: Du Guosheng, Email:duguosheng309@126.com

摘要

摘要: 目的总结肝移植术后他克莫司（FK506）导致的下肢疼痛综合征的治疗经验。方法 1例男性52岁患者，因乙型病毒性肝炎（乙肝）、肝炎后肝硬化失代偿期、肝脏恶性肿瘤行肝移植手术后应用FK506免疫抑制剂治疗后出现双下肢疼痛综合征，经排除血管神经性疼痛后，停用FK506并转化为西罗莫司（SRL）治疗，血药浓度早期维持在6~8 ng/mL，后根据移植物存活时间逐步调整。结果经转化治疗2周后，患者双下肢肿胀疼痛逐步减轻、皮肤瘙痒逐步消退，1个月后基本恢复正常活动功能，随访至投稿日无反复。结论 FK506不良反应导致的双下肢疼痛综合征较为罕见，改用SRL可规避这一不良反应。
- 肝移植 /
- 双下肢疼痛综合征 /
- 他克莫司 /
- 器官移植 /
- 甲胎蛋白 /
- 西罗莫司
Abstract: Objective To summarize the therapeutic experience of lower limb pain syndrome caused by tacrolimus (FK506) after liver transplantation. Methods A 52-year-old male patient diagnosed with virus B hepatitis (hepatitis B), post-hepatitis liver cirrhosis at the decompensation stage and malignant liver tumors developed bilateral lower limbs pain syndrome after liver transplantation with FK506 immunosuppressant. After eliminating the possibility of angioneurotic pain, FK506 was terminated and replaced by sirolimus (SRL) therapy. The blood concentration was maintained at 6~8 ng/mLduring the early stage, and then gradually adjusted according to the survival time of the liver graft. Results After 2-weeks conversion therapy, the swelling and pain of bilateral lower limbs of the patient were gradually relieved, and the skin pruritus was gradually healed. After 1 month, the patient was basically restored to normal activity and function. No recurrence was reported until the submission date of this manuscript. Conclusions Bilateral lower limbs pain syndrome caused by adverse reaction of FK506 is relatively rare. FK506 can be substituted by SRL to avoid the adverse reaction.
- Liver transplantation /
- Pain syndrome of bilateral lower limbs /
- Tacrolimus /
- Organ transplantation /
- Alpha-fetoprotein /
- Sirolimus

HTML全文

图 1 不同治疗阶段的双下肢症状比较

A图为FK506治疗阶段；B图为SRL替代治疗阶段

Figure 1. Comparison of bilateral lower limbs symptoms in different treatment stages

下载: 全尺寸图片幻灯片

图 2 术后FK506血药浓度及SRL血药浓度变化趋势

Figure 2. Changes of plasma FK506 and sirolimus concentration after operation

下载: 全尺寸图片幻灯片

参考文献(23)

[1]	ALESSIANI M, CILLO U, FUNG JJ, et al. Adverse effects of FK506 overdosage after liver transplantation[J]. Transplant Proc, 1993, 25(1 Pt 1):628-634. http://cn.bing.com/academic/profile?id=db20cda4dc0e5b32407e6a2dfd91246c&encoded=0&v=paper_preview&mkt=zh-cn
[2]	ALSINA AE. Liver transplantation for hepatocellular carcinoma[J]. Cancer Control, 2010, 17(2):83-86. doi: 10.1177/107327481001700203
[3]	ZHOU L, PAN LC, ZHENG YG, et al. Novel strategy of sirolimus plus thymalfasin and huaier granule on tumor recurrence of hepatocellular carcinoma beyond the UCSF criteria following liver transplantation: a single center experience[J]. Oncol Lett, 2018, 16(4):4407-4417. DOI: 10.3892/ol.2018.9226.
[4]	周林, 郑永根, 杜国盛, 等.肝癌肝移植术后西罗莫司转换治疗的免疫学效应分析[J].解放军医药杂志, 2017, 29(4):24-28.DOI: 10.3969/j.issn.2095-140X.2017.04.007. ZHOU L, ZHENG YG, DU GS, et al. Immunological effect of sirolimus conversion herapy on hepatic carcinoma after liver transplantation[J]. Med Pharm J Chin PLA, 2017, 29(4):24-28. DOI: 10.3969/j.issn.2095-140X.2017.04.007.
[5]	MUELLER AR, PLATZ KP, BECHSTEIN WO, et al. Neurotoxicity after orthotopic liver transplantation. a comparison between cyclosporine and FK506[J].Transplantation, 1994, 58(2):155-170. doi: 10.1097/00007890-199405820-00006
[6]	HENDRICKSON RJ, SUJKA J, FISCHER R, et al. Indications and efficacy of conversion from tacrolimus- to sirolimus-based immunosuppression in pediatric patients who underwent liver transplantation for unresectable hepatoblastoma[J].Pediatr Transplant, 2019:e13369. DOI: 10.1111/petr.13369.
[7]	RAYAR M, BARDOU-JACQUET E. Recurrence of primary biliary cholangitis after liver transplantation: is tacrolimus really worse than other drugs?[J].Gastroenterology, 2019, 156(8)2354. DOI: 10.1053/j.gastro.2019.02.047.
[8]	LEE EC, KIM SH, PARK SJ. Safety and efficacy of once-daily prolonged-release tacrolimus in living donor liver transplantation: an open-label, prospective, single-arm, phase 4 study[J]. Ann Transplant, 2018, 23:713-720. DOI: 10.12659/AOT.910618.
[9]	杜国盛, 周林, 石炳毅, 等.三联抗肿瘤疗法预防晚期原发性肝癌肝移植术后肿瘤复发的临床研究[J].器官移植, 2014, 5(2):74-78.DOI: 10.3969/j.issn.1674-7445.2014.02.004. DU GS, ZHOU L, SHI BY, et al. Clinical study of triple anti-tumor therapy for preventing tumor recurrence of terminal primary liver cancer after liver transplantation[J]. Organ Transplant, 2014, 5(2):74-78.DOI: 10.3969/j.issn.1674-7445.2014.02.004.
[10]	魏淑贞, 张德奎, 姜山, 等.肝移植术后服用他克莫司致神经毒性反应的观察[J].中国现代医学杂志, 2004, 14(6):90-91.DOI: 10.3969/j.issn.1005-8982.2004.06.032. WEI SZ, ZHANG DK, JIANG S, et al. Study on neurotoxicity of FK506 after liver transplantation[J]. Chin J Mod Med, 2004, 14(6):90-91. DOI: 10.3969/j.issn.1005-8982.2004.06.032.
[11]	LUÉ A, MARTINEZ E, NAVARRO M, et al. Donor age predicts calcineurin inhibitor induced neurotoxicity after liver transplantation[J]. Transplantation, 2019. DOI: 10.1097/TP.0000000000002750 [Epubahead of print].
[12]	邬蓉, 陈万生, 金晓玲, 等.原位肝移植术后患者早期神经毒性反应与他克莫司血药浓度的关系[J].第二军医大学学报, 2007, 28(12):1381-1382.DOI: 10.3321/j.issn:0258-879x.2007.12.025. WU R, CHEN WS, JIN XL, et al. Relationship between blood concentration of tacrolimus and neurotoxic reactions in early phase after orthotopic liver transplantation[J]. Acad J Sec Mil Med Univ, 2007, 28(12):1381-1382. DOI: 10.3321/j.issn:0258-879x.2007.12.025.
[13]	朱静楠, 张翠欣.肝移植受者他克莫司治疗窗浓度的初步探讨[J].临床合理用药杂志, 2012, 5(26):15-16. DOI: 10.3969/j.issn.1674-3296.2012.26.011. ZHU JN, ZHANG CX. Preliminary research of the therapeutic window concentration of tacrolimus in liver transplant recipients[J]. Chin J Clin Rational Drug Use, 2012, 5(26):15-16.DOI: 10.3969/j.issn.1674-3296.2012.26.011.
[14]	张骊, 田大治, 滕大洪, 等.肝移植术后肾功能不全病例分享[J/CD].实用器官移植电子杂志, 2017, 5(4):283-284. DOI: 10.3969/j.issn.2095-5332.2017.04.011. ZHANG L, TIAN DZ, TENG DH, et al. Case-sharing of renal dysfunction after liver transplantation[J/CD]. Pract J Organ Transplant (Electr Vers), 2017, 5(4):283-284. DOI: 10.3969/j.issn.2095-5332.2017.04.011.
[15]	杜国盛, 周林, 朱志东, 等. Foxp3⁺调节性T细胞与肝癌肝移植患者术后肿瘤复发关系的研究[J].器官移植, 2015, 6(5):311-315.DOI: 10.3969/j.issn.1674-7445.2015.05.007. DU GS, ZHOU L, ZHU ZD, et al. Research on the relationship between Foxp3⁺ regulatory T cell and umor recurrence of patients after liver transplantation for hepatocellular carcinoma[J]. Organ Transplant, 2015, 6(5):311-315. DOI: 10.3969/j.issn.1674-7445.2015.05.007.
[16]	周林, 杜国盛, 朱志东, 等.预防晚期肝内胆管细胞癌肝移植术后复发的三联疗法疗效报道[J/CD].中华普外科手术学杂志(电子版), 2014, 8(1):40-43. DOI: 10.3877/cma.j.issn.1674-3946.2014.01.013. ZHOU L, DU GS, ZHU ZD, et al. Prevention of recurrence of end-stage intrahepatic cholangiocellular carcinoma after liver transplantation by triple therapy[J/CD]. Chin J Oper Proced Gen Sur (Electr Vers), 2014, 8(1):40-43.DOI: 10.3877/cma.j.issn.1674-3946.2014.01.013.
[17]	周林, 索龙龙, 宋继勇, 等.以西罗莫司为基础三联抗肿瘤疗法对大鼠肝癌肝移植复发模型T淋巴细胞的影响[J].器官移植, 2014, 5(6):368-373.DOI: 10.3969/j.issn.1674-7445.2014.06.009. ZHOU L, SUO LL, SONG JY, et al. Influence of sirolimus based triple anti-tumor therapy on T lymphocyte of rat model with liver cancer recurrence after transplantation[J]. Organ Transplant, 2014, 5(6):368-373. DOI: 10.3969/j.issn.1674-7445.2014.06.009.
[18]	MORENO GONZALES M, MYHRE L, TANER T. Sublingual tacrolimus in liver transplantation: a valid option?[J]. Transplant Proc, 2016, 48(6):2102-2106. DOI: 10.1016/j.transproceed.2016.03.043.
[19]	ALTIERI M, DELAVAL G, KIMMOUN E, et al. Conversion from once-daily prolonged-release tacrolimus to once-daily extended-release tacrolimus in stable liver transplant recipients[J]. Exp Clin Transplant, 2018, 16(3):321-325. DOI: 10.6002/ect.2016.0328.
[20]	BILBAO I, DOPAZO C, CASTELLS L, et al. Immunosuppression based on everolimus in liver transplant recipients with severe early post-transplantation neurotoxicity[J]. Transplant Proc, 2014, 46(9):3104-3107. DOI: 10.1016/j.transproceed.2014.10.001.
[21]	TÖNSHOFF B, HÖCKER B. Treatment strategies in pediatric solid organ transplant recipients with calcineurin inhibitor-induced nephrotoxicity[J]. Pediatr Transplant, 2006, 10(6):721-729. DOI: 10.1111/j.1399-3046.2006.00577.x.
[22]	HE MK, LE Y, ZHANG YF, et al. Matrix metalloproteinase 12 expression is associated with tumor FOXP3⁺ regulatory T cell infiltration and poor prognosis in hepatocellular carcinoma[J]. Oncol Lett, 2018, 16(1):475-482. DOI: 10.3892/ol.2018.8642.
[23]	LEISKAU C, RAJANAYAGAM J, PFISTER ED, et al. Side effects and efficacy of renal sparing immunosuppression in pediatric liver transplantation:a single center matched cohort study[J]. Pediatr Transplant, 2018, 22(5):e13207. DOI: 10.1111/petr.13207.