Dynamics of pediatric liver allograft histological changes and the role of HLA, non-HLA antibodies.
(2015) American Association for the Study of Liver Diseases (AASLD) — Location: San Francisco, USA (13.November.2015)
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- Abstract
- Study purpose: Pediatric liver allograft histological changes are frequently seen but their significance remains unclear. Our purpose was to evaluate these changes and assess the impact of various antibodies on the liver graft. Methods: Retrospective study including children transplanted between 2004 and 2014 having known HLA and non-HLA antibody status, more than 1 protocol biopsy and under regular follow up. Children with combined organ transplant, re-transplant, chronic rejection, vascular and biliary complications were excluded. Protocol biopsies were evaluated for bile duct proliferation, portal tract inflammation and fibrosis as per the Metavir and Venturi score. Fibrosis rate was calculated as change in fibrosis score divided by duration (years) since previous biopsy. HLA antibodies were tested with solid single bead Luminex assay with MFI>1500 as cut off. Results: 103 children with 323 biopsies were included. Longer post LT duration was associated with higher grade of fibrosis over all (p<0.05) and specifically in the peri-portal zone (p=0.01). Fibrosis rate overall and in the peri-portal zone was significantly higher 0-3 years post LT in comparison to duration of 3-10 years post LT. The HLA antibodies were positive in 27% pre-LT and in 46% post LT. Post LT duration and development of HLA antibodies were significantly related (p<0.05). 80% of the HLA antibodies post LT were de-novo and donor specific (53%), non-donor specific (47%) were equally distributed. The non-HLA antibodies: ANA, SMA and LKM positivity increased post LT. Transient positivity for ANA in 20% and SMA in 31% was seen. Gama-globulin % was significantly higher (19.5%) when non-HLA antibodies were present, than when absent (15%; p<0.05). Levels >20% were associated with HLA antibody positivity (p=0.05). Histological evaluation showed increase in bile duct proliferation with post LT duration (p=0.04), HLA post-type II antibodies (p=0.05), increasing severity of overall fibrosis (p=0.001) and specifically with portal and sinusoidal fibrosis (p=0.001, 0.02). Increasing portal fibrosis was associated with portal inflammation (p=0.001). Conclusions: Pediatric liver allograft changes should be visualized as portal inflammation or non specific hepatitis that progress to portal fibrosis and biliary proliferation that result in portal or cental fibrosis. The HLA II antibodies post LT may have a role in propagating fibrosis through biliary inflammation and consequent proliferation. In non-DNAIH like histology, non HLA antibodies have a limited role. Fibrosis increases with duration post LT and progression rate is remarkable different before and after 3 years of LT.
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Varma, S., & Sokal, E. (2015). Dynamics of pediatric liver allograft histological changes and the role of HLA, non-HLA antibodies. American Association for the Study of Liver Diseases (AASLD), San Francisco, USA. https://hdl.handle.net/2078.5/229652