[1656] IHC for Foxp3, CD4 and CD8 Lymphocytes Aid in the Diagnosis of Acute Rejection vs. HCV Recurrence in Liver Transplant Biopsies

A Tholpady, G Krueger, B Zhao, RE Brown, N Tatevian. UT Health Science Center at Houston, Houston, TX

Background: End-stage liver disease due to Hep C is the most common indication for liver transplantation. Fresh donor liver transplant is inevitably doomed to recurrent HCV (rHCV) in these patients, which is further complicated by the risk of acute rejection (AR). Distinguishing between the two can be a diagnostic challenge by H & E alone. In this study, we used the IHC markers CD4, CD8 and Foxp3-a marker for regulatory Tcells (Tregs)-to aid in diagnosis.
Design: Biopsies from explant liver and donor pre- and post-transplant over the course of 132 weeks were stained with H&E and scored for rHCV and AR by the Scheuer system and rejection activity index (RAI). IHC was performed with Foxp3, CD4 and CD8. Average numbers of positive cells were calculated in 10 high power fields in liver lobules (LL) and in 10 portal areas (PA) in each biopsy.
Results: As seen here:

Quantity of Foxp3 and CD8 cells in PAs and LL

Diagnosis	Time (weeks)	CD8/hpf	CD8/PA	Foxp3/hpf	Foxp3/PA
Explant (cirrhotic liver, S 3-4)	0	2.2	32.2	0.8	7
No AR, no rHCV	1.4	3.6	29.4	0.4	3
Donor pre-transplant	0	3.8	8	0.2	3.8
rHCV (G 2/4, S 1/4) no AR	132	4.8	81.3	1.8	7.6
rHCV (G 2/4, S 1/4), AR?	111	8.3	50	3.7	9
rHCV (G 2/4, S 1/4), AR?	85.7	10	88	1.8	23.9
rHCV (G 3/4, S 3/4), RAI=6/9	60	28.9	206	4.3	33.5
rHCV (G3/4, S 1/4), RAI=5/9	128	33.2	138	6.1	33.8
RAI 7/9	9	33.7	102.5	0.9	2.2

hpf=40x mag., rHCV=grade and stage

CD8 cells are markedly increased in LL from biopsies with AR alone or concurrent AR and rHCV (>28/hpf) in comparison to biopsies without AR (<10/hpf). Foxp3 cells in LL were decreased in AR alone (<1/hpf) vs. rHCV (>1.7/hpf). The distribution of both CD8 and Foxp3 in PAs showed a similar but less correlative trend. A striking pattern was observed in biopsies with both AR and rHCV where CD4 cells formed nodules in portal areas while CD8 cells remained predominantly in the periphery.


Conclusions: In cases with AR, CD8 lymphocytes were remarkably increased in a diffuse manner. Foxp3 lymphocytes were rarely seen in AR but increased in # when rHCV occured. Our preliminary results show these immunohistochemical markers to be useful in diagnosing AR and rHCV.
Category: Liver & Pancreas

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 216, Monday Morning