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亲属活体肝移植治疗婴儿Crigler-Najjar综合征Ⅰ型1例并文献复习

顾广祥 宗志鹏 周韬 夏强

顾广祥, 宗志鹏, 周韬, 等. 亲属活体肝移植治疗婴儿Crigler-Najjar综合征Ⅰ型1例并文献复习[J]. 器官移植, 2020, 11(4): 471-476. doi: 10.3969/j.issn.1674-7445.2020.04.008
引用本文: 顾广祥, 宗志鹏, 周韬, 等. 亲属活体肝移植治疗婴儿Crigler-Najjar综合征Ⅰ型1例并文献复习[J]. 器官移植, 2020, 11(4): 471-476. doi: 10.3969/j.issn.1674-7445.2020.04.008
Gu Guangxiang, Zong Zhipeng, Zhou Tao, et al. Living related donor liver transplantation for infant with Crigler-Najjar syndrome type Ⅰ: a report of one case and literature review[J]. ORGAN TRANSPLANTATION, 2020, 11(4): 471-476. doi: 10.3969/j.issn.1674-7445.2020.04.008
Citation: Gu Guangxiang, Zong Zhipeng, Zhou Tao, et al. Living related donor liver transplantation for infant with Crigler-Najjar syndrome type Ⅰ: a report of one case and literature review[J]. ORGAN TRANSPLANTATION, 2020, 11(4): 471-476. doi: 10.3969/j.issn.1674-7445.2020.04.008

亲属活体肝移植治疗婴儿Crigler-Najjar综合征Ⅰ型1例并文献复习

doi: 10.3969/j.issn.1674-7445.2020.04.008
基金项目: 

国家自然科学基金青年项目 81700570

详细信息
    作者简介:

    顾广祥,男,1985年生,博士,住院医师,研究方向为儿童肝移植,Email:guguangxiang@163.com

    通讯作者:

    夏强,男,1966年生,博士,主任医师,研究方向为肝移植,Email:xiaqiang@shsmu.edu.cn

  • 中图分类号: R617, R596

Living related donor liver transplantation for infant with Crigler-Najjar syndrome type Ⅰ: a report of one case and literature review

More Information
  • 摘要:   目的  总结克里格勒-纳贾尔综合征(CNS)Ⅰ型的亲属活体肝移植治疗效果。  方法  1例男性3月龄患儿,出生后4 d无明显诱因下出现皮肤、巩膜进行性黄染,完善相关检查后排除其他诱因,并经基因检测鉴定为CNS Ⅰ型。其母亲作为供者,行亲属活体肝移植术。术后常规应用免疫抑制方案,并根据生化指标及受者细胞色素P450(CYP)3A5基因型调整他克莫司剂量。  结果  受者术后7 d肝酶恢复正常,胆红素逐日下降并于术后22 d降至正常范围。随访至投稿日,受者皮肤巩膜黄染褪去,胆红素正常,肝酶稳定,一般情况佳,生活质量高。  结论  活体肝移植可治疗CNS Ⅰ型所带来的高非结合胆红素血症等病症,极大提高患者的生活质量。

     

  • 图  1  肝移植术前通过EDDA IQQA-Liver系统预估血管走向及供肝体积

    注:A图为肝静脉分割走形;B图为门静脉分割走形;C图为肝动脉分割走形;D图为供肝体积评估。

    Figure  1.  Prediction of vascular direction and donor livervolume by EDDA IQQA-liver system before liver transplantation

    图  2  患儿肝脏脏面大体观

    Figure  2.  General view of the visceral surface of the child's liver

    表  1  肝移植治疗CNS Ⅰ型患者的预后

    Table  1.   Prognosis of CNS Ⅰ patients treated with liver transplantation

    研究作者 年份 手术方式 原发病(n 存活率(%)
    1年 5年 10年 其他
    Adam R, et al[20] 2012 OLT、LDLT、ALT、DLT CNS(59) 88、97 79、92 79、92 79、92(15年)
    86、100 76、95
    Arnon R, et al[21] 2010 OLT、LDLT、ALT 代谢性肝病(446)包括CNS(21) 94.6 88.9
    Sze YK, et al[22] 2009 OLT、LDLT、ALT 代谢性肝病(96)包括CNS Ⅰ(11) 83、91 77、86 62、82
    Strauss KA, et al[23] 2006 OLT CNS Ⅰ(4)CNS Ⅱ(1) 100(16年)
    Ozçay F, et al[24] 2009 LDLT CNS Ⅰ(4) 75
    Morioka D, et al[25] 2005 LDLT 代谢性肝病(46)包括CNS Ⅰ(2) 86.9 81.2 81.2
    Morioka D, et al[26] 2005 LDLT 代谢性肝病(21)包括CNS Ⅰ(2) 85.7 85.7
    Valmiki S, et al[27] 2020 LDLT CNS Ⅰ(1) 100
    Rela M, et al[28] 1999 ALT CNS Ⅰ(6) 100
    Shanmugam NP, et al[29] 2019 ALT 代谢性肝病(13)包括CNS(5) 100 100
    Celik N, et al[30] 2019 DLT 代谢性肝病(4)包括CNS(2) 100
    注:①为1988年至2009年移植物、受者存活率。
    ②为1999年至2009年移植物、受者存活率。
    ③为移植物、受者存活率。
    ④—为无数据。
    下载: 导出CSV
  • [1] FAGIUOLI S, DAINA E, D'ANTIGA L, et al. Monogenic diseases that can be cured by liver transplantation[J]. J Hepatol, 2013, 59(3):595-612. DOI: 10.1016/j.jhep.2013.04. 004.
    [2] VAN DIJK R, MAYAYO-PERALTA I, ARONSON SJ, et al. Disruption of HNF1α binding site causes inherited severe unconjugated hyperbilirubinemia[J]. J Hepatol, 2015, 63(6):1525-1529. DOI: 10.1016/j.jhep.2015.07.027.
    [3] CRIGLER JF JR, NAJJAR VA. Congenital familial nonhemolytic jaundice with kernicterus[J]. Pediatrics, 1952, 10(2):169-180. http://www.ncbi.nlm.nih.gov/pubmed/14884759?dopt=Abstract
    [4] SHI X, ARONSON S, KHAN AS, et al. A novel UGT1A1 gene mutation causing severe unconjugated hyperbilirubinemia: a case report[J]. BMC Pediatr, 2019, 19(1):173. DOI: 10.1186/s12887-019-1555-y.
    [5] EBRAHIMI A, RAHIM F. Crigler-Najjar syndrome: current perspectives and the application of clinical genetics[J]. Endocr Metab Immune Disord Drug Targets, 2018, 18(3):201-211. DOI: 10.2174/1871530318666171213153130.
    [6] CANU G, MINUCCI A, ZUPPI C, et al. Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database[J]. Blood Cells Mol Dis, 2013, 50(4):273-280. DOI: 10.1016/j.bcmd.2013.01.003.
    [7] ZUBAIDA B, CHEEMA HA, HASHMI MA, et al. Spectrum of UGT1A1 variants in Pakistani children affected with inherited unconjugated hyperbilirubinemias[J]. Clin Biochem, 2019, 69:30-35. DOI: 10.1016/j.clinbiochem.2019.05.012.
    [8] ELFAR W, JÄRVINEN E, JI W, et al. A novel pathogenic UGT1A1 variant in a Sudanese child with type 1 Crigler-Najjar syndrome[J]. Drug Metab Dispos, 2019, 47(1):45-48. DOI: 10.1124/dmd.118.084368.
    [9] GAILITE L, ROTS D, PUKITE I, et al. Case report: multiple UGT1A1 gene variants in a patient with Crigler-Najjar syndrome[J]. BMC Pediatr, 2018, 18(1):317. DOI: 10.1186/s12887-018-1285-6.
    [10] 杨琳, 丁俊杰, 周文浩.UGT1A1基因多态性与新生儿黄疸遗传关联性的Meta分析[J].中国循证儿科杂志, 2010, 5(5):335-348.DOI:10.3969/j.issn.1673-5501. 2010.05.004.

    YANG L, DING JJ, ZHOU WH. Association between polymorphisms of UDP-glucuronosyltransferase 1A1 gene and jaundice in neonates: a Meta-analysis[J]. Chin J Evid Based Pediatr, 2010, 5(5):335-348. DOI: 10.3969/j.issn.1673-5501.2010.05.004.
    [11] 熊清芳, 钟艳丹, 冯晓宁, 等.遗传性非溶血性非结合型胆红素血症UGT1A1突变谱研究[J].中华肝脏病杂志, 2018, 26(12):898-902.DOI: 10.3760/cma.j.issn.1007-3418.2018.12.005.

    XIONG QF, ZHONG YD, FENG XN, et al. Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia[J]. Chin J Hepatol, 2018, 26(12):898-902. DOI: 10.3760/cma.j.issn.1007-3418.2018.12.005.
    [12] ABUDUXIKUER K, FANG LJ, LI LT, et al. UGT1A1 genotypes and unconjugated hyperbilirubinemia phenotypes in post-neonatal Chinese children: a retrospective analysis and quantitative correlation[J]. Medicine (Baltimore), 2018, 97(49):e13576. DOI: 10.1097/MD.0000000000013576.
    [13] STRAUSS KA, AHLFORS CE, SOLTYS K, et al. Crigler-Najjar syndrome type 1: pathophysiology, natural history, and therapeutic frontier[J]. Hepatology, 2020, 71(6):1923-1939. DOI: 10.1002/hep.30959.
    [14] RAZEK AAKA, TAMAN SE, EL REGAL ME, et al. Diffusion tensor imaging of microstructural changes in the gray and white matter in patients with Crigler-Najjar syndrome type I[J]. J Comput Assist Tomogr, 2020, DOI: 10.1097/RCT.0000000000001008[Epubahead of print].
    [15] BENTIVEGNA A, SANTAMBROGIO J, CLERICI M. UGT1A1 mutations and psychoses: towards understanding the relationship with unconjugated bilirubin[J]. CNS Spectr, 2019:1-3. DOI: 10.1017/S1092852919001251.
    [16] ARIAS IM, GARTNER LM, COHEN M, et al. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. clinical, biochemical, pharmacologic and genetic evidence for heterogeneity[J]. Am J Med, 1969, 47(3):395-409. doi: 10.1016/0002-9343(69)90224-1
    [17] LUND HT, JACOBSEN J. Influence of phototherapy on the biliary bilirubin excretion pattern in newborn infants with hyperbilirubinemia[J]. J Pediatr, 1974, 85(2):262-267. doi: 10.1016/S0022-3476(74)80408-7
    [18] MAISELS MJ, MCDONAGH AF. Phototherapy for neonatal jaundice[J]. N Engl J Med, 2008, 358(9):920-928. DOI: 10.1056/NEJMct0708376.
    [19] MAZARIEGOS G, SHNEIDER B, BURTON B, et al. Liver transplantation for pediatric metabolic disease[J]. Mol Genet Metab, 2014, 111(4):418-427. DOI: 10.1016/j.ymgme.2014.01.006.
    [20] ADAM R, KARAM V, DELVART V, et al. Evolution of indications and results of liver transplantation in Europe. a report from the European Liver Transplant Registry (ELTR)[J]. J Hepatol, 2012, 57(3):675-688. DOI: 10.1016/j.jhep.2012.04.015.
    [21] ARNON R, KERKAR N, DAVIS MK, et al. Liver transplantation in children with metabolic diseases: the studies of pediatric liver transplantation experience[J]. Pediatr Transplant, 2010, 14(6):796-805. DOI: 10.1111/j.1399-3046.2010.01339.x.
    [22] SZE YK, DHAWAN A, TAYLOR RM, et al. Pediatric liver transplantation for metabolic liver disease: experience at King's College Hospital[J]. Transplantation, 2009, 87(1):87-93. DOI: 10.1097/TP.0b013e31818bc0c4.
    [23] STRAUSS KA, ROBINSON DL, VREMAN HJ, et al. Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease[J]. Eur J Pediatr, 2006, 165(5):306-319. doi: 10.1007/s00431-005-0055-2
    [24] OZÇAY F, ALEHAN F, SEVMIŞ S, et al. Living related liver transplantation in Crigler-Najjar syndrome type 1[J]. Transplant Proc, 2009, 41(7):2875-2877. DOI: 10.1016/j.transproceed.2009.07.025.
    [25] MORIOKA D, KASAHARA M, TAKADA Y, et al. Living donor liver transplantation for pediatric patients with inheritable metabolic disorders[J]. Am J Transplant, 2005, 5(11):2754-2763. doi: 10.1111/j.1600-6143.2005.01084.x
    [26] MORIOKA D, TAKADA Y, KASAHARA M, et al. Living donor liver transplantation for noncirrhotic inheritable metabolic liver diseases: impact of the use of heterozygous donors[J]. Transplantation, 2005, 80(5):623-628. doi: 10.1097/01.tp.0000167995.46778.72
    [27] VALMIKI S, MANDAPATI KK, MIRIYALA LKV, et al. A case report of a novel 22 bp duplication within exon 1 of the UGT1A1 in a Sudanese infant with Crigler-Najjar syndrome type I[J]. BMC Gastroenterol, 2020, 20(1):62. DOI: 10.1186/s12876-020-01192-4.
    [28] RELA M, MUIESAN P, VILCA-MELENDEZ H, et al. Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome type I[J]. Ann Surg, 1999, 229 (4):565-569. doi: 10.1097/00000658-199904000-00017
    [29] SHANMUGAM NP, VALAMPARAMPIL JJ, REDDY MS, et al. Auxiliary partial orthotopic liver transplantation for monogenic metabolic liver diseases: single-centre experience[J]. JIMD Rep, 2019, 45:29-36. DOI: 10.1007/ 8904_2018_137.
    [30] CELIK N, SQUIRES JE, SOLTYS K, et al. Domino liver transplantation for select metabolic disorders: expanding the living donor pool[J]. JIMD Rep, 2019, 48(1):83-89. DOI: 10.1002/jmd2.12053.
    [31] DHAWAN A, LAWLOR MW, MAZARIEGOS GV, et al. Disease burden of Crigler-Najjar syndrome: systematic review and future perspectives[J]. J Gastroenterol Hepatol, 2020, 35(4):530-543. DOI: 10.1111/jgh.14853.
    [32] FAMULARI ES, NAVARRO-TABLEROS V, HERRERA SANCHEZ MB, et al. Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice[J]. Sci Rep, 2020, 10(1):887. DOI: 10.1038/s41598-020-57820-2.
    [33] FOURRIER A, DELBOS F, MENORET S, et al. Regenerative cell therapy for the treatment of hyperbilirubinemic gunn rats with fresh and frozen human induced pluripotent stem cells-derived hepatic stem cells[J]. Xenotransplantation, 2020, 27(1):e12544. DOI: 10.1111/xen.12544.
    [34] GRUBBS BH, CHING MM, PARDUCHO KR, et al. Ultrasound-guided in utero transplantation of placental stem cells into the liver of Crigler-Najjar syndrome model rat[J]. Transplantation, 2019, 103(7):e182-e187. DOI: 10.1097/TP.0000000000002735.
    [35] SMETS F, DOBBELAERE D, MCKIERNAN P, et al. Phase I/Ⅱ trial of liver-derived mesenchymal stem cells in pediatric liver-based metabolic disorders: a prospective, open label, multicenter, partially randomized, safety study of one cycle of heterologous human adult liver-derived progenitor cells (hepastem) in urea cycle disorders and Crigler-Najjar syndrome patients[J]. Transplantation, 2019, 103(9):1903-1915. DOI: 10.1097/TP.0000000000002605.
    [36] APGAR JF, TANG JP, SINGH P, et al. Quantitative systems pharmacology model of hUGT1A1-modRNA encoding for the UGT1A1 enzyme to treat Crigler-Najjar syndrome type 1[J]. CPT Pharmacometrics Syst Pharmacol, 2018, 7(6):404-412. DOI: 10.1002/psp4.12301.
    [37] ARONSON SJ, VERON P, COLLAUD F, et al. Prevalence and relevance of pre-existing anti-adeno-associated virus immunity in the context of gene therapy for Crigler-Najjar syndrome[J]. Hum Gene Ther, 2019, 30(10):1297-1305. DOI: 10.1089/hum.2019.143.
    [38] COLLAUD F, BORTOLUSSI G, GUIANVARC'H L, et al. Preclinical development of an AAV8-hUGT1A1 vector for the treatment of Crigler-Najjar syndrome[J]. Mol Ther Methods Clin Dev, 2018, 12:157-174. DOI: 10.1016/j.omtm.2018.12.011.
    [39] 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. http://d.old.wanfangdata.com.cn/Periodical/zsykdxxb201904002

    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. http://d.old.wanfangdata.com.cn/Periodical/zsykdxxb201904002
    [40] AL SHURAFA H, WALI S, CHEHAB MS, et al. Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia[J]. Clin Transplant, 2002, 16(3):222-226. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=9efaca9f0089317df655d63df5c4e8a3
    [41] ISKANDER I, GAMALELDIN R, EL HOUCHI S, et al. Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy[J]. Pediatrics, 2014, 134(5):e1330-e1339. DOI: 10.1542/peds.2013-1764.
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出版历程
  • 收稿日期:  2020-03-26
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2020-07-15

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