Morphometric assessment of liver fibrosis may enhance early diagnosis of biliary atresia

2013 ◽  
Vol 9 (4) ◽  
pp. 330-335 ◽  
Author(s):  
Ahmed F. Abdalla ◽  
Abeer Fathy ◽  
Khaled R. Zalata ◽  
Ahmed Megahed ◽  
Ahmed Abo-Alyazeed ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Early Diagnosis ◽  
Biliary Atresia ◽  
Morphometric Assessment

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

scholarly journals Increased MMP‐7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia

2016 ◽  
Vol 2 (3) ◽  
pp. 187-198 ◽  
Author(s):  
Anna Kerola ◽  
Hanna Lampela ◽  
Jouko Lohi ◽  
Päivi Heikkilä ◽  
Annika Mutanen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Biliary Epithelium ◽  
Native Liver

scholarly journals YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Zheng ◽  
Jiaqian Luo ◽  
Yifan Yang ◽  
Rui Dong ◽  
Fa-Xing Yu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Biliary Atresia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Hippo Signaling ◽  
Mice Model ◽  
Hippo Signaling Pathway ◽  
Ductal Cells

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.

scholarly journals Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Sun ◽  
Menghua Xu ◽  
Peijun Zhuang ◽  
Gong Chen ◽  
Kuiran Dong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Transforming Growth Factor ◽  
Serum Vitamin ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Serum Vitamin D ◽  
Duct Ligation ◽  
Tgf Β1

AbstractTo investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

490c – C1Inh: A Novel Therapeutic Target to Treat Biliary Atresia and Liver Fibrosis

2019 ◽  
Vol 156 (6) ◽  
pp. S-1507
Author(s):  
Nazanin Navabi ◽  
Sridevi Gutta ◽  
Reena Mourya ◽  
Kevin Holmes ◽  
Andrea Iskenderian ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Therapeutic Target ◽  
Novel Therapeutic

scholarly journals Quantitative Liver Fibrosis Using Collagen Hybridizing Peptide to Predict Native Liver Survival in Biliary Atresia

2020 ◽  
Vol 70 (1) ◽  
pp. 87-92
Author(s):  
Catalina Jaramillo ◽  
Stephen L. Guthery ◽  
Amy Lowichik ◽  
Gregory Stoddard ◽  
Taegun Kim ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Native Liver ◽  
Native Liver Survival

scholarly journals Associations between Vitamin D and Liver Function and Liver Fibrosis in Patients with Biliary Atresia

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Peijun Zhuang ◽  
Song Sun ◽  
Rui Dong ◽  
Gong Chen ◽  
Yanlei Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Liver Fibrosis ◽  
Liver Function ◽  
Confidence Interval ◽  
Biliary Atresia ◽  
Odds Ratio ◽  
Intraoperative Cholangiography ◽  
Preoperative Serum ◽  
Histopathologic Features

Objectives. To detail the effects of vitamin D (VD) deficiency and assess the relationships between VD deficiency and liver function and liver fibrosis in patients with biliary atresia (BA). Methods. In this study, BA patients confirmed by intraoperative cholangiography were enrolled between January 2017 and February 2019. Preoperative serum 25-(OH)D level, liver function, serum biomarker levels of liver fibrosis, and histopathologic features were recorded. Deficiency, insufficiency, and sufficiency of VD were defined as serum 25-(OH)D concentrations of <10, 10-20, and >20 ng/ml, respectively. Associations between serum 25-(OH)D level and liver function and liver fibrosis were analyzed. Results. A total of 161 BA infants were included. The median (interquartile range (IQR)) serum 25-(OH)D level in all patients was 7.56 (IQR: 4.48–11.40) ng/ml. The rates of 25-(OH)D deficiency, insufficiency, and sufficiency were 67.1% (108/161), 29.2% (47/161), and 3.7% (6/161), respectively. Serum 25-(OH)D level was negatively correlated with alkaline phosphatase (r=‐0.232, P=0.003). After adjusting for age, a decrease in serum 25-(OH)D level was correlated with the increase of the Batts-Ludwig stage score (odds ratio (OR): 0.94, 95% confidence interval (CI): 0.88–0.99; P=0.028). Serum 25-(OH)D level was also correlated with the N-terminal propeptide of type III procollagen (PIIINP) (r=‐0.246, P=0.002). Additionally, PIIINP (P=0.038) and ALP (P=0.031) were independently associated with serum 25-(OH)D level. Conclusions. VD deficiency was common and inversely correlated with liver fibrosis in BA patients. Furthermore, VD was not correlated with liver function except alkaline phosphatase.

scholarly journals microRNA-21 expressions impact on liver fibrosis in biliary atresia patients

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Akhmad Makhmudi ◽  
Alvin Santoso Kalim ◽  
Gunadi
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia
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