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  1. Article ; Online: Expression of fibrosis-related genes in liver allografts: Association with histology and long-term outcome after pediatric liver transplantation.

    Voutilainen, Silja H / Kosola, Silja K / Lohi, Jouko / Jahnukainen, Timo / Pakarinen, Mikko P / Jalanko, Hannu

    Clinical transplantation

    2021  Volume 35, Issue 8, Page(s) e14373

    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. ...

    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.
    MeSH term(s) Allografts/pathology ; Child ; Fibrosis ; Humans ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Liver Transplantation
    Language English
    Publishing date 2021-06-27
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.14373
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2204: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Expression of 6 Biomarkers in Liver Grafts After Pediatric Liver Transplantation: Correlations with Histology, Biochemistry, and Outcome.

    Voutilainen, Silja H / Kosola, Silja K / Lohi, Jouko / Mutka, Aino / Jahnukainen, Timo / Pakarinen, Mikko / Jalanko, Hannu

    Annals of transplantation

    2020  Volume 25, Page(s) e925980

    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 AND METHODS We evaluated ... ...

    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 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.
    MeSH term(s) Adolescent ; Biomarkers ; Biopsy ; Child ; Child, Preschool ; Female ; Fibrosis ; Humans ; Infant ; Liver/pathology ; Liver Cirrhosis/etiology ; Liver Cirrhosis/pathology ; Liver Transplantation/adverse effects ; Male
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-10-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1484710-3
    ISSN 2329-0358 ; 1425-9524
    ISSN (online) 2329-0358
    ISSN 1425-9524
    DOI 10.12659/AOT.925980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Liver and serum expression of matrix metalloproteinases in asymptomatic pediatric liver transplant recipients.

    Voutilainen, Silja H / Kosola, Silja K / Tervahartiala, Taina I / Sorsa, Timo A / Jalanko, Hannu J / Pakarinen, Mikko P

    Transplant international : official journal of the European Society for Organ Transplantation

    2016  Volume 30, Issue 2, Page(s) 124–133

    Abstract: We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post-LT and age- ... ...

    Abstract We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post-LT and age-matched controls for analyses of MMPs and TIMPs. Patients with fibrosis had significantly higher hepatic gene expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 than patients without. Expression of these genes correlated with graft Metavir fibrosis stage (r = 0.494-0.684, P ≤ 0.006 for all). Gene expression of MMP-1, MMP-3, MMP-8, TIMP-3, and TIMP-4 was undetectable in both patients and controls. Portal inflammation and cytokeratin 7 correlated positively with gene expression of TIMP-1. Gene expression of MMP-2, MMP-9, and TIMP-2 correlated negatively with the time of low-dose cortisone usage (r = -0.448 to -0.422, P < 0.05 for all). Serum concentrations of MMP-8 and TIMP-1 were significantly increased and MMP-9 decreased among patients compared with controls, but no correlations to graft histology or gene expression were observed. Hepatic gene expression of certain MMPs and TIMPs is increased in stable pediatric LT recipients displaying graft fibrosis, but this did not reflect to their serum concentrations. Increased hepatic gene expression of TIMP-1 correlated with graft fibrosis stage, inflammation, and chronic cholestasis.
    MeSH term(s) Adolescent ; Adult ; Child ; Cross-Sectional Studies ; Female ; Fibrosis ; Gene Expression ; Humans ; Immunosuppression ; Keratin-7/metabolism ; Liver/enzymology ; Liver/pathology ; Liver Transplantation ; Male ; Matrix Metalloproteinases/blood ; Tissue Inhibitor of Metalloproteinases/blood ; Young Adult
    Chemical Substances Keratin-7 ; Tissue Inhibitor of Metalloproteinases ; Matrix Metalloproteinases (EC 3.4.24.-)
    Language English
    Publishing date 2016-12-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 639435-8
    ISSN 1432-2277 ; 0934-0874
    ISSN (online) 1432-2277
    ISSN 0934-0874
    DOI 10.1111/tri.12879
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2358: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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