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肝移植：急性细胞排斥反应的诊断

Author
K Rajender Reddy, MD
Section Editor
Robert S Brown, Jr, MD, MPH
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF
Translators
曾勇, 主任医师，教授

引言

尽管免疫抑制治疗已有所改善，但肝移植物排斥反应仍然是肝移植患者发生并发症和晚期移植物丢失的重要原因[1-6]。

在该疾病谱的一端，许多通过计划性肝活检发现有局灶性或轻度排斥反应组织学特征的患者即使不接受治疗也可能保持移植物功能稳定[7]。有假设认为，这种通过移植肝脏进行的淋巴细胞迁移会促进一定程度免疫耐受的发生。另一方面，有5%-10%的发生了急性细胞排斥反应的肝移植受者尽管接受了抗排斥治疗，仍然会进展至严重的胆管消失性排斥反应[8]。这些患者可能需要再次移植。

下文将介绍肝移植后急性细胞排斥反应的临床表现和诊断。该并发症的治疗以及移植免疫生物学将单独讨论。 (参见“肝移植急性细胞排斥反应的治疗”和“移植免疫生物学”)

排斥反应的发生时间及危险因素

早期急性细胞排斥反应大多发生在肝移植后90日内。早期急性排斥反应不会对移植物或患者结局造成不良影响，但因丙型肝炎病毒(hepatitis C virus, HCV)感染移植的患者除外，这些患者快速给予糖皮质激素治疗的结局较差[9-11]。晚期细胞排斥反应常与环孢素或他克莫司血药浓度低有关，并且已被发现与移植物存活率降低有关[2,12-14]。以下是一些最大型病例系列研究结果的举例：

●一项纳入762例肝移植连续成人受者的队列研究显示，490例(64%)患者发生过至少1次排斥反应，其中大部分发生在移植后最初6周[15]。这些患者中约有20%在移植后1年内发生了第2次排斥反应。

          

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Literature review current through: 2017-06 . | This topic last updated: 2017-06-15.
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References
Top
  1. Wiesner RH, Ludwig J, van Hoek B, Krom RA. Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure. Hepatology 1991; 14:721.
  2. Klintmalm GB, Nery JR, Husberg BS, et al. Rejection in liver transplantation. Hepatology 1989; 10:978.
  3. Emond JC, Thistlethwaite JR, Baker AL. Rejection in liver allograft recipients: Clinical characterization and management. Clin Transpl 1987; 1:143.
  4. Ascher NL, Stock PG, Bumgardner GL, et al. Infection and rejection of primary hepatic transplant in 93 consecutive patients treated with triple immunosuppressive therapy. Surg Gynecol Obstet 1988; 167:474.
  5. Oguma S, Belle S, Starzl TE, Demetris AJ. A histometric analysis of chronically rejected human liver allografts: insights into the mechanisms of bile duct loss: direct immunologic and ischemic factors. Hepatology 1989; 9:204.
  6. Krom RA, Wiesner RH, Rettke SR, et al. The first 100 liver transplantations at the Mayo Clinic. Mayo Clin Proc 1989; 64:84.
  7. McVicar JP, Kowdley KV, Bacchi CE, et al. The natural history of untreated focal allograft rejection in liver transplant recipients. Liver Transpl Surg 1996; 2:154.
  8. Soin AS, Rasmussen A, Jamieson NV, et al. CsA levels in the early posttransplant period--predictive of chronic rejection in liver transplantation? Transplantation 1995; 59:1119.
  9. Neuberger J, Adams DH. What is the significance of acute liver allograft rejection? J Hepatol 1998; 29:143.
  10. Dousset B, Conti F, Cherruau B, et al. Is acute rejection deleterious to long-term liver allograft function? J Hepatol 1998; 29:660.
  11. Samonakis DN, Germani G, Burroughs AK. Immunosuppression and HCV recurrence after liver transplantation. J Hepatol 2012; 56:973.
  12. Adams DH, Neuberger JM. Patterns of graft rejection following liver transplantation. J Hepatol 1990; 10:113.
  13. Mor E, Gonwa TA, Husberg BS, et al. Late-onset acute rejection in orthotopic liver transplantation--associated risk factors and outcome. Transplantation 1992; 54:821.
  14. Anand AC, Hubscher SG, Gunson BK, et al. Timing, significance, and prognosis of late acute liver allograft rejection. Transplantation 1995; 60:1098.
  15. Wiesner RH, Demetris AJ, Belle SH, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998; 28:638.
  16. Ramji A, Yoshida EM, Bain VG, et al. Late acute rejection after liver transplantation: the Western Canada experience. Liver Transpl 2002; 8:945.
  17. Bennett-Guerrero E, Feierman DE, Barclay GR, et al. Preoperative and intraoperative predictors of postoperative morbidity, poor graft function, and early rejection in 190 patients undergoing liver transplantation. Arch Surg 2001; 136:1177.
  18. Taner T, Stegall MD, Heimbach JK. Antibody-mediated rejection in liver transplantation: current controversies and future directions. Liver Transpl 2014; 20:514.
  19. Bathgate AJ, Hynd P, Sommerville D, Hayes PC. The prediction of acute cellular rejection in orthotopic liver transplantation. Liver Transpl Surg 1999; 5:475.
  20. Rosen HR, Corless CL, Rabkin J, Chou S. Association of cytomegalovirus genotype with graft rejection after liver transplantation. Transplantation 1998; 66:1627.
  21. Abraham SC, Furth EE. Receiver operating characteristic analysis of serum chemical parameters as tests of liver transplant rejection and correlation with histology. Transplantation 1995; 59:740.
  22. Williams JW, Peters TG, Vera SR, et al. Biopsy-directed immunosuppression following hepatic transplantation in man. Transplantation 1985; 39:589.
  23. Henley KS, Lucey MR, Appelman HD, et al. Biochemical and histopathological correlation in liver transplant: the first 180 days. Hepatology 1992; 16:688.
  24. Adams DH, Wang L, Hubscher SG, et al. Soluble interleukin-2 receptors in serum and bile of liver transplant recipients. Lancet 1989; 1:469.
  25. Perkins JD, Nelson DL, Rakela J, et al. Soluble interleukin-2 receptor level as an indicator of liver allograft rejection. Transplantation 1989; 47:77.
  26. Adams DH, Mainolfi E, Elias E, et al. Detection of circulating intercellular adhesion molecule-1 after liver transplantation--evidence of local release within the liver during graft rejection. Transplantation 1993; 55:83.
  27. Adams DH, Burnett D, Stockley RA, et al. Biliary beta 2-microglobulin in liver allograft rejection. Hepatology 1988; 8:1565.
  28. Foster PF, Sankary HN, Hart M, et al. Blood and graft eosinophilia as predictors of rejection in human liver transplantation. Transplantation 1989; 47:72.
  29. Hoffmann MW, Wonigeit K, Steinhoff G, et al. Tumor necrosis factor alpha and interleukin-1 beta in rejecting human liver grafts. Transplant Proc 1991; 23:1421.
  30. Umeshita K, Monden M, Tono T, et al. Determination of the presence of interleukin-6 in bile after orthotopic liver transplantation. Its role in the diagnosis of acute rejection. Ann Surg 1996; 223:204.
  31. Kim C, Aono S, Marubashi S, et al. Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation. J Surg Res 2012; 175:138.
  32. Asaoka T, Kato T, Marubashi S, et al. Differential transcriptome patterns for acute cellular rejection in recipients with recurrent hepatitis C after liver transplantation. Liver Transpl 2009; 15:1738.
  33. Massoud O, Heimbach J, Viker K, et al. Noninvasive diagnosis of acute cellular rejection in liver transplant recipients: a proteomic signature validated by enzyme-linked immunosorbent assay. Liver Transpl 2011; 17:723.
  34. Farid WR, Pan Q, van der Meer AJ, et al. Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transpl 2012; 18:290.
  35. Bubak ME, Porayko MK, Krom RA, Wiesner RH. Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy. Hepatology 1991; 14:1063.
  36. Larson AM, Chan GC, Wartelle CF, et al. Infection complicating percutaneous liver biopsy in liver transplant recipients. Hepatology 1997; 26:1406.
  37. Banff schema for grading liver allograft rejection: an international consensus document. Hepatology 1997; 25:658.
  38. Snover DC, Freese DK, Sharp HL, et al. Liver allograft rejection. An analysis of the use of biopsy in determining outcome of rejection. Am J Surg Pathol 1987; 11:1.
  39. Demetris AJ, Qian SG, Sun H, Fung JJ. Liver allograft rejection: an overview of morphologic findings. Am J Surg Pathol 1990; 14 Suppl 1:49.
  40. Foster PF, Sankary HN, Williams JW, et al. Morphometric inflammatory cell analysis of human liver allograft biopsies. Transplantation 1991; 51:873.
  41. Foster PF, Bhattacharyya A, Sankary HN, et al. Eosinophil cationic protein's role in human hepatic allograft rejection. Hepatology 1991; 13:1117.
  42. Ludwig J, Gross JB Jr, Perkins JD, Moore SB. Persistent centrilobular necroses in hepatic allografts. Hum Pathol 1990; 21:656.
  43. Bellamy CO, Herriot MM, Harrison DJ, Bathgate AJ. C4d immunopositivity is uncommon in ABO-compatible liver allografts, but correlates partially with lymphocytotoxic antibody status. Histopathology 2007; 50:739.
  44. Wilson CH, Agarwal K, Carter V, et al. Late humoral rejection in a compliant ABO-compatible liver transplant recipient. Transplantation 2006; 82:988.
  45. Höroldt BS, Burattin M, Gunson BK, et al. Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation? Liver Transpl 2006; 12:1144.
  46. Wright TL, Donegan E, Hsu HH, et al. Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 1992; 103:317.
  47. Ferrell LD, Wright TL, Roberts J, et al. Hepatitis C viral infection in liver transplant recipients. Hepatology 1992; 16:865.
  48. Petrovic LM, Villamil FG, Vierling JM, et al. Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation. Liver Transpl Surg 1997; 3:398.
  49. Regev A, Molina E, Moura R, et al. Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation. Liver Transpl 2004; 10:1233.
  50. Sreekumar R, Rasmussen DL, Wiesner RH, Charlton MR. Differential allograft gene expression in acute cellular rejection and recurrence of hepatitis C after liver transplantation. Liver Transpl 2002; 8:814.
  51. Williams JW, Vera S, Peters TG, et al. Cholestatic jaundice after hepatic transplantation. A nonimmunologically mediated event. Am J Surg 1986; 151:65.
  52. Goldstein NS, Hart J, Lewin KJ. Diffuse hepatocyte ballooning in liver biopsies from orthotopic liver transplant patients. Histopathology 1991; 18:331.
  53. Hübscher SG, Adams DH, Buckels JA, et al. Massive haemorrhagic necrosis of the liver after liver transplantation. J Clin Pathol 1989; 42:360.
  54. Oda T, Yamashi S, Ohoka H, et al. A case of hemolytic anemia resulting from autoantibody in renal transplantation — study of autoanti-A or autoanti-B. Transplant Proc 1985; 17:2294.
  55. Jenkins RL, Georgi BA, Gallik-Karlson CA, et al. ABO mismatch and liver transplantation. Transplant Proc 1987; 19:4580.