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Silja H. Voutilainen, Silja K. Kosola, Jouko Lohi, Aino Mutka, Timo Jahnukainen, Mikko Pakarinen, Hannu Jalanko
(Pediatric Surgery and Pediatric Transplantation Surgery, Pediatric Liver and Gut Research Group, Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland)
Ann Transplant 2020; 25:e925980
Subclinical graft inflammation and fibrosis after pediatric liver transplantation (LT) are common. Biomarkers are needed that precede and are associated with these changes and graft outcome.
MATERIAL AND METHODS: We evaluated immunohistochemical expression of 6 biomarkers [alpha-smooth muscle actin (alpha-SMA), collagen I, decorin, vimentin, P-selectin glycoprotein ligand-1 (PSGL-1), and CD34] in biopsies taken intraoperatively at LT (baseline) (n=29) and at 11.3 years after LT (first follow-up) (n=51). Liver biochemistry and graft histology were assessed at the first follow-up and at final assessment (19.6 years after LT) (n=48). Second follow-up biopsies for histology were available from 24 patients. The immunostainings were correlated with liver histology, biochemistry, and outcome at these time-points.
RESULTS: Baseline levels of the biomarkers were unrelated to presence of fibrosis at follow-up. Increased alpha-SMA, collagen I levels, decorin, and vimentin were associated with simultaneous fibrosis at the first follow-up (p=0.001-0.027). Increased SMA, collagen I, decorin, vimentin, PSGL-1, and CD34 expression at first follow-up were associated with simultaneous portal inflammation (p=0.001-0.025). alpha-SMA, decorin, and vimentin expression were increased in patients without fibrosis at the first follow-up but who developed fibrosis in second follow-up (p=0.014 p=0.024 and p=0.024). Significant fibrosis (F2) and markedly increased alpha-SMA, collagen I, decorin, and vimentin levels at first follow-up were associated with suboptimal liver status at the final assessment (p=0.002-0.042).
CONCLUSIONS: The expression of the biomarkers at LT was unrelated to later development of graft fibrosis. a-SMA, decorin, and vimentin were associated with later graft fibrosis and suboptimal liver status.