A clinical research consortium sponsored by NIAID
Demetris AJ, Ruppert K, Ekong U, Rosenthal P, Sayre P, Tchao N, Feng S
Department of Pathology, University of Pittsburgh, PA Department of Pediatrics, Northwestern University, Chicago, IL Department of Pediatrics, University of California San Francisco, CA Immune Tolerance Network, San Francisco, CA Department of Surgery, University of California San Francisco, CA
Background:The prevalence of histopathologic abnormalities in stable pediatric living-related liver transplant (tx) recipients is largely unknown.
Methods: Histomorphometric analyses of protocol biopsies (bxs) from an ITN-sponsored study of immunosuppression withdrawal obtained from 8 pediatric recipients of living related liver grafts 5-12 yrs after tx (Table 1) were compared to 8 normal controls matched to the gender and current age of the historic liver donors. Bx length and width, portal tract #, central vein (CV) #, portal sinusoidal length and, for each portal tract, inflammation profile, portal vein (PV), hepatic artery (HA), and bile duct (BD) #s were measured. Architectural distortion, glycogen vacuolization of periportal hepatocyte nuclei, steatosis, and sinusoidal fibrosis were semi-quantitatively scored. Cohorts were compared; differences were analyzed by chi-square and Wilcoxon Rank Sum tests. Differences in PV, HA, BD, and inflammation were analyzed by hierarchical linear models adjusting for within-bx correlations.
Results: Pediatric allograft bx findings overlapped with those of controls but showed greater architectural distortion (p<.001), higher % of portal tract lacking PVs (p<.003), decreased CV# / µm2 bx (p<.02), and more patchy subsinusoidal fibrosis and glycogen vacuolization (p<.06). All other parameters were comparable. No allograft bxs showed immunologic injury or a specific disease process.
Conclusions: Architectural integrity of long-surviving living related liver grafts overlaps with normal livers. They show alterations possibly reflecting microcirculation disturbances perhaps best classified as nodular regenerative hyperplasia. Whether these changes are more common in partial grafts merits further study. Our findings have implications for liver growth, regeneration, and repair.
