Background: Unexplained graft fibrosis and inflammation are common after pediatric liver transplantation (LT).
Objective: We investigated the graft expression of fibrogenic genes and correlated the findings with transplant histopathology and outcome.
Methods: Liver biopsies from 29 recipients were obtained at a median of 13.1 (IQR: 5.0-18.4) years after pediatric LT. Control samples were from six liver-healthy subjects. Hepatic expression of 40 fibrosis-related genes was correlated to histological findings: normal histology, fibrosis with no inflammation, and fibrosis with inflammation. Liver function was evaluated after a subsequent follow-up of 9.0 years (IQR: 8.0-9.4).
Results: Patients with fibrosis and no inflammation had significantly increased gene expression of profibrotic TGF-β3 (1.17 vs. 1.02 p = .005), CTGF (1.64 vs. 0.66 p = .014), PDGF-α (1.79 vs. 0.98 p = .049), PDGF -β (0.99 vs. 0.76 p = .006), integrin-subunit-β1 (1.19 vs. 1.02 p = .045), α-SMA (1.12 vs. 0.58 p = .013), type I collagen (0.82 vs. 0.53 p = .005) and antifibrotic decorin (1.15 vs. 0.99 p = .045) compared to patients with normal histology. mRNA expression of VEGF A (0.84 vs. 1.06 p = .049) was lower. Only a few of the studied genes were upregulated in patients with both fibrosis and inflammation. The gene expression levels showed no association with later graft outcome.
Conclusions: Altered hepatic expression of fibrosis-related genes is associated with graft fibrosis without concurrent inflammation.
Keywords: fibrosis; gene expression; inflammation; liver transplantation; pediatrics.
© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.