The Pre-Senescence Features of Chronic Liver Allograft Rejection Can Be Recognized Prior to Full Development of Banff-Defined Criteria
Sara Hafezi-Bakhtiari, Oyedele A Adeyi. University Health Network, University of Toronto, Toronto, ON, Canada
Background: Chronic rejection (CR) is one of the most serious complications of allograft liver transplant and even though it occurs at a rate of 3% over 5 years, it has great impact on allograft outcome and survival. Banff criteria are used to diagnose CR when specific parameters are documented in biopsy. We however describe series of changes we believe precede earliest Banff criteria of bile duct senescence in majority of sampled ducts, which could help in earlier diagnosis and timely intervention of CR.
Design: Histologically documented CR biopsies between 2003 and 2011, who had at least one biopsy prior (pre-CR) to the one that ultimately diagnosed CR were identified. Clinical information was retrieved from transplant electronic record and corresponding biopsies reviewed. Control biopsies include 10 cases of allograft liver due to recurrent HCV (rHCV) and 10 of proven obstruction.
Results: Twenty-two biopsies in 22 patients with CR were included of which 15 (68.2%) had what we have called pre-senescence changes. These include 7 female and 8 male [ages: 20-69 years (mean 47); time from transplant to CR diagnosis: 13d-84 months (mean: 28months); time between pre-CR and diagnostic CR biopsies: 4 d-16 months (mean 5.8 months.
Features attributable to poor bile drainage seen in periportal areas in 15 of 22 pre-CR biopsies are:
-Peri-portal small cell change with high N: C ratio
-No significant ductular proliferation (confirmed by CK7 immunostain)
-Early but sparse intermediate cells /biliary metaplasia of periportal hepatocytes
-Occasional but less than 50% senescence features in terminal bile ducts
-No significant (i.e. less than 30%) duct loss.
Alkaline Phosphatase was increased in all 15 patients at the time of pre-CR biopsies. 7 of 22 patients showed 0-1 of the above features probably attributed to longer interval between pre-CR and CR biopsies (11.1 months compared to 5.8 months). None of the rHCV showed the above features, but some were seen in obstruction biopsies, although these in addition had ductular reaction and intermediate cells by CK7 was more pronounced in obstruction than pre-CR biopsies.
Conclusions: Our observation suggests that these histologic findings might represent early CR features resulting from relative bile stasis and preceding morphologic evidence of significant duct atrophy/senescence and/or loss. Recognizing and validating these features will help in earlier diagnosis and intervention of patients in whom CR process is already evolving, but could not meet current diagnostic criteria for CR.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 149, Tuesday Afternoon