Expression of fibrosis‐related genes in liver allografts: Association with histology and long‐term outcome after pediatric liver transplantation. Issue 8 (27th June 2021)

• Record Type: Journal Article
• Authors: Voutilainen, Silja H.; Kosola, Silja K.; Lohi, Jouko; Jahnukainen, Timo; Pakarinen, Mikko P.; Jalanko, Hannu
• Is Part Of: Clinical transplantation. Volume 35:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-27
• Subjects: fibrosis -- gene expression -- inflammation -- liver transplantation -- pediatrics; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ctr.14373
• Languages: English
• ISSNs: 0902-0063

Abstract

Abstract: 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.