Multi-disciplinary team of complex cholestatic liver injury after liver transplantation
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摘要:
目的 探讨多学科综合诊疗(MDT)在肝移植术后复杂胆汁淤积型肝损伤中的作用。 方法 对吉林大学第一医院肝移植中心2020年6月23日收治的1例肝移植术后复杂胆汁淤积型肝损伤病例进行MDT讨论,明确病因及治疗策略,并总结MDT在肝移植术后复杂胆汁淤积型肝损伤治疗中的作用。 结果 患者肝移植术后肝功能异常,先后明确诊断为胆道狭窄、排斥反应及胆道感染,内镜逆行胰胆管成像(ERCP)支架内外双引流、糖皮质激素冲击、抗感染等治疗效果不佳。经MDT讨论,明确诊断为肝移植术后复杂胆汁淤积型肝损伤,建议在病理辅助排除排斥反应基础上优化免疫抑制方案,行针对性抗感染治疗,并预防可能伴随出现的药物性肝损伤。后患者恢复良好,治愈出院。 结论 肝移植术后复杂胆汁淤积型肝损伤病因复杂,病情动态变化,通过MDT讨论可提高对该疾病的认知和加强对诊治思路的梳理,提高治疗的针对性和有效性。 Abstract:Objective To investigate the role of multi-disciplinary team (MDT) in the treatment of complex cholestatic liver injury after liver transplantation. Methods MDT consultation was conducted to clarify the causes and therapeutic strategies for one case of complex cholestatic liver injury after liver transplantation admitted to Liver Transplantation Center of the First Hospital of Jilin University on June 23, 2020. And the role of MDT in the treatment of complex cholestatic liver injury after liver transplantation was summarized. Results The patient presented with abnormal liver function after liver transplantation. The diagnosis of biliary stricture, rejection and biliary tract infection was confirmed successively. Endoscopic retrograde cholangiopancreatography (ERCP) stent internal and external double drainage, glucocorticoid shock and anti-infection therapy yielded low clinical efficacy. After MDT consultation, complex cholestatic liver injury after liver transplantation was confirmed. It was suggested to optimize the immunosuppressive regimen based on the exclusion of rejections by pathological examination, deliver targeted anti-infection interventions and prevent the potential risk of concomitant drug-induced liver injury. The patient was discharged after proper recovery. Conclusions The causes of complex cholestatic liver injury after liver transplantation are diverse, and the condition changes dynamically. MDT consultation are performed to deepen the understanding of this disease, strengthen the classification of diagnosis and treatment ideas and enhance the precision and efficacy of corresponding treatment. -
图 2 首次ERCP后移植肝病理学表现
注:A图示肝腺泡/小叶结构维持正常,肝细胞胆汁淤积、毛细胆管胆栓,汇管区扩张,可见重度混合性炎症细胞浸润(苏木素-伊红,×100);B图为A图箭头处放大,肝窦略有扩张,中央静脉管腔扩张,周围融合坏死伴有出血,中央静脉内皮炎(苏木素-伊红,×200);C图为A图星号处放大,汇管区可见中度混合性炎症细胞浸润,未见明显界面炎,汇管区小胆管可辨,轻度增生,炎症细胞攻击小胆管,致胆管上皮排列不整,未见明显门静脉支内皮炎,汇管区间质未见明显纤维组织增生(苏木素-伊红,×400)。
Figure 2. Pathological manifestations of liver allograft after the first ERCP
图 3 第2次ERCP后移植肝病理学表现
注:A图示肝腺泡/小叶结构维持正常,肝细胞胆汁淤积、毛细胆管胆栓,肝窦略有扩张,汇管区轻度扩张,可见轻度混合性炎症细胞浸润(苏木素-伊红,× 200);B图示肝细胞胆汁淤积、毛细胆管胆栓,部分肝小叶内见胆汁湖形成(苏木素-伊红,× 200);C图示汇管区可见中度混合性炎症细胞浸润,未见明显界面炎,汇管区小胆管轻度增生,胆管上皮排列不整齐,较多中性粒细胞围绕胆管,并见胆栓,未见明显门静脉支内皮炎,汇管区间质未见明显纤维组织增生(苏木素-伊红,× 200)。
Figure 3. Pathological manifestations of liver allograft after the second ERCP
表 1 患者不同时期肝功能变化情况
Table 1. Changes of liver function of the patient in different periods
日期 AST(U/L) ALT(U/L) GGT(U/L) ALP(U/L) TB(μmol/L) DB(μmol/L) TBA(μmol/L) 7月6日(第1次ERCP术后) 318 45 275 605 101.5 66.2 107.0 7月11日(激素冲击治疗后) 128 32 434 690 181.6 109.8 122.1 7月20日(第2次ERCP术后) 69 46 450 365 210.2 116.1 22.7 7月23日(MDT讨论后1 d) 59 43 456 396 196.0 102.5 24.3 7月31日(MDT讨论后1周) 71 38 514 403 159.7 80.3 49.3 8月14日(MDT讨论后3周) 36 25 452 386 69.7 53.3 6.5 8月24日(出院) 32 15 419 452 52.1 29.2 59.8 -
[1] DAR WA, SULLIVAN E, BYNON JS, et al. Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms[J]. Liver Int, 2019, 39(5): 788-801. DOI: 10.1111/liv.14091. [2] 胡利琳, 王玮珺, 杨玲. 肝细胞型胆汁淤积诊治进展[J]. 实用肝脏病杂志, 2020, 23(1): 后插4-后插8. DOI: 10.3969/j.issn.1672-5069.2020.01.043.HU LL, WANG WJ, YANG L. Diagnosis and treatment ofparenchymal jaundice: a type of cholestasis[J]. J Pract Hepatol, 2020, 23(1): back insert 4- back insert 8. DOI: 10.3969/j.issn.1672-5069.2020.01.043. [3] 申弘, 胡萌, 魏泽辉, 等. 胆汁的生成、分泌、排泄及胆汁淤积发生机制[J]. 临床肝胆病杂志, 2019, 35(2): 431-437. DOI: 10.3969/j.issn.1001-5256.2019.02.043.SHEN H, HU M, WEI ZH, et al. Bile formation, secretion, and excretion and the pathogenesis of cholestasis[J]. J Clin Hepatol, 2019, 35(2): 431-437. DOI: 10.3969/j.issn.1001-5256.2019.02.043. [4] YOKODA RT, RODRIGUEZ EA. Review: pathogenesis of cholestatic liver diseases[J]. World J Hepatol, 2020, 12(8): 423-435. DOI: 10.4254/wjh.v12.i8.423. [5] HEATHCOTE EJ. Diagnosis and management of cholestatic liver disease[J]. Clin Gastroenterol Hepatol, 2007, 5(7): 776-782. DOI: 10.1016/j.cgh.2007.05.008. [6] European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases[J]. J Hepatol, 2009, 51(2): 237-267. DOI: 10.1016/j.jhep.2009.04.009. [7] 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 胆汁淤积性肝病诊断和治疗共识(2015)[J]. 实用肝脏病杂志, 2016, 19(6): 771-781. DOI: 10.3969/j.issn.1672-5069.2016.06.040.Branch of Hepatology of Chinese Medical Association, Branch of Gastroenterology of Chinese Medical Association, Branch of Infectious Diseases of Chinese Medical Association. Consensus on the diagnosis and treatment of cholestasis liver diseases (2015)[J]. J Pract Hepatol, 2016, 19(6): 771-781. DOI: 10.3969/j.issn.1672-5069.2016.06.040. [8] 陈虹, 王旭, 张庆, 等. 肝移植术后中远期黄疸的原因分析与治疗[J]. 中华器官移植杂志, 2012, 33(2): 97-100. DOI: 10.3760/cma.j.issn.0254-1785.2012.02.008.CHEN H, WANG X, ZHANG Q, et al. Etiological analysis and treatment of jaundice after liver transplantation during mid-later stage[J]. Chin J Organ Transplant, 2012, 33(2): 97-100. DOI: 10.3760/cma.j.issn.0254-1785.2012.02.008. [9] 赵川, 陈虹, 范铁艳, 等. 成人肝移植术后中远期胆汁淤积性肝病的研究现状[J]. 中华灾害救援医学, 2016, 4(3): 170-173. DOI: 10.13919/j.issn.2095-6274.2016.03.014.ZHAO C, CHEN H, FAN TY, et al. Research status of medium and long term cholestatic liver disease after liver transplantation in adults[J]. Chin J Disaster Med, 2016, 4(3): 170-173. DOI: 10.13919/j.issn.2095-6274.2016.03.014. [10] LO RC, CHAN KK, CHOK KS, et al. Liver allograft biopsies with histological cholestasis: a clinicopathological study of 254 cases from a single centre[J]. J Clin Pathol, 2018, 71(1): 72-78. DOI: 10.1136/jclinpath-2017-204334. [11] DE VRIES Y, VON MEIJENFELDT FA, PORTE RJ. Post-transplant cholangiopathy: classification, pathogenesis, and preventive strategies[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(4 Pt B): 1507-1515. DOI: 10.1016/j.bbadis.2017.06.013. [12] ANGELICO R, GERLACH UA, GUNSON BK, et al. Severe unresolved cholestasis due to unknown etiology leading to early allograft failure within the first 3 months of liver transplantation[J]. Transplantation, 2018, 102(8): 1307-1315. DOI: 10.1097/TP.0000000000002139. [13] DEMETRIS AJ, BELLAMY C, HÜBSCHER SG, et al. 2016 comprehensive update of the Banff Working Group on liver allograft pathology: introduction of antibody-mediated rejection[J]. Am J Transplant, 2016, 16(10): 2816-2835. DOI: 10.1111/ajt.13909. [14] MONTANO-LOZA AJ, BHANJI RA, WASILENKO S, et al. Systematic review: recurrent autoimmune liver diseases after liver transplantation[J]. Aliment Pharmacol Ther, 2017, 45(4): 485-500. DOI: 10.1111/apt.13894. [15] MONTANO-LOZA AJ, HANSEN BE, CORPECHOT C, et al. Factors associated with recurrence of primary biliary cholangitis after liver transplantation and effects on graft and patient survival[J]. Gastroenterology, 2019, 156(1): 96-107. DOI: 10.1053/j.gastro.2018.10.001. [16] HILDEBRAND T, PANNICKE N, DECHENE A, et al. Biliary strictures and recurrence after liver transplantation for primary sclerosing cholangitis: a retrospective multicenter analysis[J]. Liver Transpl, 2016, 22(1): 42-52. DOI: 10.1002/lt.24350. [17] NEVENS F. PBC-transplantation and disease recurrence[J]. Best Pract Res Clin Gastroenterol, 2018, 34/35: 107-111. DOI: 10.1016/j.bpg.2018.09.001. [18] TRONINA O, ŚLUBOWSKA K, MIKOŁAJCZYK-KORNIAK N, et al. Fibrosing cholestatic hepatitis C after liver transplantation: therapeutic options before and after introduction of direct-acting antivirals: our experience and literature review[J]. Transplant Proc, 2017, 49(6): 1409-1418. DOI: 10.1016/j.transproceed.2017.01.077. [19] LLOVET LP, SCIARRONE S, RODRÍGUEZ-TAJES S, et al. Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation[J]. Gastroenterol Hepatol, 2020, 43(1): 14-21. DOI: 10.1016/j.gastrohep.2019.07.006. [20] SEMBERA S, LAMMERT C, TALWALKAR JA, et al. Frequency, clinical presentation, and outcomes of drug-induced liver injury after liver transplantation[J]. Liver Transpl, 2012, 18(7): 803-810. DOI: 10.1002/lt.23424. [21] GONZÁLEZ-DIÉGUEZ ML, VISO VIDAL D, MENDOZA PACAS GE, et al. Tacrolimus-induced cholestatic hepatitis in a patient with liver transplant[J]. Transplantation, 2018, 102(10): e454-e456. DOI: 10.1097/TP.0000000000002332. [22] VÉLEZ-GONZÁLEZ F, BALLESTER V, ANTÚNEZ I, et al. Rejection, recurrence, or something else?[J]. Bol Asoc Med P R, 2016, 108(2): 39-41. [23] KOHLI DR, DESAI MV, KENNEDY KF, et al. Patients with post-transplant biliary strictures have significantly higher rates of liver transplant failure and rejection: a nationwide inpatient analysis[J]. J Gastroenterol Hepatol, 2021, 36(7): 2008-2014. DOI: 10.1111/jgh.15388. [24] 蔡云石, 刘雄威, 肖衡, 等. 肝移植术后胆道并发症的诊治[J/CD]. 中华肝脏外科手术学电子杂志, 2018, 7(5): 391-395. DOI: 10.3877/cma.j.issn.2095-3232.2018.05.011.CAI YS, LIU XW, XIAO H, et al. Biliary complications after liver transplantation: diagnosis and treatments[J/CD]. Chin J Hepatic Surg (Electr Edit), 2018, 7(5): 391-395. DOI: 10.3877/cma.j.issn.2095-3232.2018.05.011. [25] LARGHI A, TRINGALI A, RIMBAŞ M, et al. Endoscopic management of benign biliary strictures after liver transplantation[J]. Liver Transpl, 2019, 25(2): 323-335. DOI: 10.1002/lt.25358. [26] 中华医学会器官移植学分会. 中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)[J]. 器官移植, 2021, 12(1): 8-14, 28. DOI: 10.3969/j.issn.1674-7445.2021.01.002.Branch of Organ Transplantation of Chinese Medical Association. Diagnosis and treatment specification for immunosuppressive therapy and rejection of liver transplantation in China (2019 edition)[J] Organ Transplant, 2021, 12(1): 8-14, 28. DOI: 10.3969/j.issn.1674-7445.2021.01.002. [27] 杨雪, 涂荣芳, 杨晋辉. 药物性肝损伤的研究进展[J]. 临床肝胆病杂志, 2020, 36(3): 509-513. DOI: 10.3969/j.issn.1001-5256.2020.03.006.YANG X, TU RF, YANG JH. Research advances in drug-induced liver injury[J]. J Clin Hepatol, 2020, 36(3): 509-513. DOI: 10.3969/j.issn.1001-5256.2020.03.006.