Failed Allografts

The reasons for liver allograft failure vary with the time since transplantation(1-6). Primary dysfunction because of ischemic/preservation injury and hepatic artery thrombosis and subsequent bile duct necrosis are the most common causes of liver within the first several weeks. Humoral and severe acute cellular rejection also occur during this time, but they are uncommon causes of early allograft failure. Frequently, a combination of the above factors ultimately contribute to deterioration of graft function(1-6).

Between 2-3 weeks and 6 months after transplantation, delayed complications of early technical problems, such as the biliary sludge syndrome from ischemic cholangitis(7, 8), acute rejection and rapidly developing cases of chronic rejection(9, 10) are the major causes of graft failure. There are still graft failures that occur more than 6 months after transplantation, as a result of delayed technical complications. These usually involve the hepatic artery and subsequently, the biliary tree. An imperfect arterial anastomosis results in turbulent blood flow and accelerated atherosclerosis, which is limited to the immediate downstream side of the anastomosis. The intra-hepatic arterial branches are unaffected(unpublished observation). As the time since transplantation increases, recurrence of the original non-neoplastic and neoplastic diseases and chronic rejection account for an increasing percentage of graft failures.

The principle goal of the gross and histopathological examination is to provide, as precise as possible, the reason(s) for allograft failure. This requires both a detailed pathological examination, including review of any previous biopsies, and clinical correlation with the recipient surgeon and medical management team. Failure to filter the pathology findings through the screen of clinical events, often results in a purely descriptive surgical pathology report. These are difficult to incorporate into a patient management scheme, and provide inadequate data for retrospective academic analysis of patient and graft survival.

The actual approach to the gross pathological examination is similar to that described for native hepatectomy specimens, but significantly more attention is given to the hilar structures, including the hepatic artery, biliary tree and portal vein. This is particularly true early after transplantation, when technical problems related to anastomotic thrombosis and/or breakdown frequently cause or contribute to graft failure. It is our practice to first, grossly identify the hepatic artery resection margin, the end of which is frequently clipped, and to longitudinally open the hepatic artery and its primary branches into the right and left lobes. Then, the same is done for the biliary tree and then the portal venous system. This sequence is chosen because arterial thrombosis and stenosis frequently underlie biliary tract necrosis, sludge and inflammation and if the ductal system is examined first, the underlying arterial pathology might be obscured. The portal venous system is examined last, because it is infrequently the site of pathology and the cause graft injury. As the time after transplantation increases, gross examination of the failed allografts is virtually identical to that of native hepatectomy specimens, but it is still important to examine the integrity of the hilar structures.

Microscopic sections are taken according to the same protocol used for the native hepatectomy specimens(9), which includes one cassette of the biliary, hepatic arterial, and portal vein resection margins in the hilum(superficial hilum); a section from the deep hilum, which includes first and second order branches of the hepatic arterial tree and peribiliary glands; and sections from the subcapsular and deep aspects of the right and left lobes. Ample sampling and photography of any gross defects is intuitive. We also routinely save bulk frozen and formalin-fixed tissue tissue in a tissue bank for academic research purposes.


  1. Demetris AJ, Tsamandas AC, Delaney CP, Abu-Elmagd K, Fung JJ, Starzl TE. Pathology of Liver Transplantation. Transplantation of the Liver. Orlando: W. B. Saunders Company, 1996:681-723.
  2. Backman L, Gibbs J, Levy M, et al. Causes of late graft loss after liver transplantation. Transplantation 1993;55(5):1078-82.
  3. Quiroga J, Colina I, Demetris AJ, et al. Cause and timing of first allograft failure in orthotopic liver transplantation: a study of 177 consecutive patients. Hepatology 1991;14(6):1054-1062.
  4. Wozney P, Zajko AB, Bron KM, et al. Vascular complications after liver transplantation: a 5-year experience. AJR Am J Roentgenol 1986;147(4):657-663.
  5. Marino IR, Doyle HR, Aldrighetti L, et al. - Effect of donor age and sex on the outcome of liver transplantation. Hepatology 1995;22(6):1754-1762.
  6. Yersiz H, Shaked A, Olthoff K, et al. - Correlation between donor age and the pattern of liver graft recovery after transplantation [see comments]. Transplantation 1995;60(8):790-794.
  7. Ludwig J, Batts KP, MacCarty RL. Ischemic cholangitis in hepatic allografts. Mayo Clin Proc 1992;67(6):519-526.
  8. Demetris AJ. Ischemic cholangitis [editorial; comment]. Mayo Clin Proc 1992;67(6):601-602.
  9. Demetris AJ, Jaffe R, Starzl TE. A review of adult and pediatric post-transplant liver pathology. [Review]. Pathol Annu 1987;22(2):347-386.
  10. Ludwig J, Wiesner RH, Batts KP, et al. The acute vanishing bile duct syndrome (acute irreversible rejection) after orthotopic liver transplantation. Hepatology 1987;7(3):476-483.

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