UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Liver transplantation: Diagnosis of acute cellular rejection

Author
K Rajender Reddy, MD
Section Editor
Robert S Brown, Jr, MD, MPH
Deputy Editor
Kristen M Robson, MD, MBA, FACG

INTRODUCTION

Despite improvements in immunosuppressive therapy, hepatic allograft rejection remains an important cause of morbidity and late graft loss in patients undergoing liver transplantation [1-6].

At one end of the spectrum, graft function may remain stable in many patients found to have focal or mild histologic features of rejection on a protocol liver biopsy, even when no treatment is provided [7]. Such lymphocyte trafficking through the allograft has been hypothesized to contribute to the development of a degree of immunological tolerance. On the other hand, approximately 5 to 10 percent of liver transplantation recipients who develop acute cellular rejection progress to severe ductopenic rejection despite antirejection therapy [8]. These patients may require retransplantation.

The clinical manifestations and diagnosis of acute cellular liver transplantation rejection are described below. The treatment of this complication and a review of transplantation immunobiology are discussed separately. (See "Treatment of acute cellular rejection in liver transplantation" and "Transplantation immunobiology".)

EPIDEMIOLOGY AND OUTCOMES

Acute rejection in liver transplant recipients is an important clinical event and identification of risk factors for rejection may permit a more individualized approach to immunosuppressive therapy.

In a study of two large cohorts of liver transplant recipients, at least one biopsy-proven acute rejection episode occurred in 27 percent recipients in the Adult to Adult Living Donor Liver Transplantation (A2ALL) cohort and in 15.6 percent recipients in Scientific Registry of Transplant Recipients (SRTR) cohort [9].

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2017. | This topic last updated: Jun 15, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
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. Levitsky J, Goldberg D, Smith AR, et al. Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients. Clin Gastroenterol Hepatol 2017; 15:584.
  10. Neuberger J, Adams DH. What is the significance of acute liver allograft rejection? J Hepatol 1998; 29:143.
  11. Dousset B, Conti F, Cherruau B, et al. Is acute rejection deleterious to long-term liver allograft function? J Hepatol 1998; 29:660.
  12. Wiesner RH, Demetris AJ, Belle SH, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998; 28:638.
  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. 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.
  16. Rosen HR, Corless CL, Rabkin J, Chou S. Association of cytomegalovirus genotype with graft rejection after liver transplantation. Transplantation 1998; 66:1627.
  17. Ramji A, Yoshida EM, Bain VG, et al. Late acute rejection after liver transplantation: the Western Canada experience. Liver Transpl 2002; 8:945.
  18. Taner T, Stegall MD, Heimbach JK. Antibody-mediated rejection in liver transplantation: current controversies and future directions. Liver Transpl 2014; 20:514.
  19. 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.
  20. Williams JW, Peters TG, Vera SR, et al. Biopsy-directed immunosuppression following hepatic transplantation in man. Transplantation 1985; 39:589.
  21. Henley KS, Lucey MR, Appelman HD, et al. Biochemical and histopathological correlation in liver transplant: the first 180 days. Hepatology 1992; 16:688.
  22. Adams DH, Wang L, Hubscher SG, et al. Soluble interleukin-2 receptors in serum and bile of liver transplant recipients. Lancet 1989; 1:469.
  23. Perkins JD, Nelson DL, Rakela J, et al. Soluble interleukin-2 receptor level as an indicator of liver allograft rejection. Transplantation 1989; 47:77.
  24. 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.
  25. Adams DH, Burnett D, Stockley RA, et al. Biliary beta 2-microglobulin in liver allograft rejection. Hepatology 1988; 8:1565.
  26. Foster PF, Sankary HN, Hart M, et al. Blood and graft eosinophilia as predictors of rejection in human liver transplantation. Transplantation 1989; 47:72.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. Shaked A, Chang BL, Barnes MR, et al. An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection. Hepatology 2017; 65:269.
  33. 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.
  34. Larson AM, Chan GC, Wartelle CF, et al. Infection complicating percutaneous liver biopsy in liver transplant recipients. Hepatology 1997; 26:1406.
  35. Banff schema for grading liver allograft rejection: an international consensus document. Hepatology 1997; 25:658.
  36. 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.
  37. 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.
  38. Foster PF, Sankary HN, Williams JW, et al. Morphometric inflammatory cell analysis of human liver allograft biopsies. Transplantation 1991; 51:873.
  39. Foster PF, Bhattacharyya A, Sankary HN, et al. Eosinophil cationic protein's role in human hepatic allograft rejection. Hepatology 1991; 13:1117.
  40. Ludwig J, Gross JB Jr, Perkins JD, Moore SB. Persistent centrilobular necroses in hepatic allografts. Hum Pathol 1990; 21:656.
  41. 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.
  42. Wilson CH, Agarwal K, Carter V, et al. Late humoral rejection in a compliant ABO-compatible liver transplant recipient. Transplantation 2006; 82:988.
  43. 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.
  44. Williams JW, Vera S, Peters TG, et al. Cholestatic jaundice after hepatic transplantation. A nonimmunologically mediated event. Am J Surg 1986; 151:65.
  45. Goldstein NS, Hart J, Lewin KJ. Diffuse hepatocyte ballooning in liver biopsies from orthotopic liver transplant patients. Histopathology 1991; 18:331.
  46. Hübscher SG, Adams DH, Buckels JA, et al. Massive haemorrhagic necrosis of the liver after liver transplantation. J Clin Pathol 1989; 42:360.
  47. 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.
  48. Jenkins RL, Georgi BA, Gallik-Karlson CA, et al. ABO mismatch and liver transplantation. Transplant Proc 1987; 19:4580.