Expression of 6 Biomarkers in Liver Grafts After Pediatric Liver Transplantation: Correlations with Histology, Biochemistry, and Outcome

Abstract

Background 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/Methods We evaluated immunohistochemical expression of 6 biomarkers [α-smooth muscle actin (α-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 α-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). α-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 α-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. α-SMA, decorin, and vimentin were associated with later graft fibrosis and suboptimal liver status.

Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism)

“…Haematoxylin‐eosin and Masson’s trichrome stainings were used for histological analysis. Immunohistochemical stainings on formalin‐fixed autopsy samples were performed as previously reported 19 . Immunohistochemical grading was done semiquantitatively by the first and last authors on a scale of 0–3 for each marker.…”

“…Immunohistochemical stainings on formalinfixed autopsy samples were performed as previously reported. 19 Immunohistochemical grading was done semiquantitatively by the first and last authors on a scale of 0-3 for each marker. At least 20 visual fields per sample were analysed.…”

Hovenia dulcis: a Chinese medicine that plays an essential role in alcohol-associated liver disease

“…Myricetin inhibits the higher TGF-β1 after ethanol exposure, potentially suppressing hepatic fibrosis ( Zhao et al, 2018 ). Alpha-smooth muscle actin (a-SMA) is a marker of activated HSCs, which is responsible for the overproduction of ECM components and the development of fibrosis ( Voutilainen et al, 2020 ). Upon stimulation with TGF-β, HSCs begin to differentiate from a quiescent state into proliferating and fibrotic myofibroblasts that express and secrete α-SMA and type I collagen (CoI-l), CoI-III and CoI-IV, leading to hepatic fibrosis ( Chang et al, 2023 ).…”

The MORPHOLOGICAL AND FUNCTIONAL ASSESSMENT OF FAP+ AND Α-Sma+-Cells IN DIFFERENT TIMES OF RAT TOXIC LIVER FIBROSIS

“…Углубленное изучение источника миофибробластов и понимание молекулярных механизмом, регулирующих изменение фенотипа клеток печени в фиброгенную линию, имеют фундаментальное значения для разработки антифибротических препаратов [1-4, 11, 15]. При фиброзе органов миофибробласты преимущественно идентифицируют с помощью маркеров α-SMA (активированные ЖК) и FAP (активированные ПФ) [16][17][18]. В большинстве органов в условиях нормы уровни мРНК и белка FAP были низкими, за исключением молочной железы, эндометрия матки, поджелудочной железы, плаценты и кожи.…”