Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia

Wilasco, Maria Inês A.; Cruz, Carolina Uribe; Santetti, Daniele; Pfaffenseller, Bianca; Dornelles, Cristina; Silveira, Themis Reverbel da

doi:10.1159/000447364

Cited by 6 publications

(3 citation statements)

References 28 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain-derived neurotrophic factor (BDNF) was recently used as a marker for the nutritional status in children and adolescents with liver cirrhosis due to biliary atresia [ 35 ]. The analysis in Wilasco et al was limited to serum BDNF controls in 53 BA patients and 33 healthy controls, with correlation to the nutritional status and the height for age ration, but has indeed shown lower serum BDNF levels in the cirrhosis group.…”

Section: Discussionmentioning

confidence: 99%

Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia

Madadi-Sanjani

Froemmel

Falk

et al. 2021

JCM

View full text Add to dashboard Cite

Background: Biliary atresia (BA) is a neonatal cholangiopathy characterized by progressive destruction of the biliary system resulting in liver cirrhosis. Residual bile drainage can temporarily be achieved through Kasai portoenterostomy (KPE) and some children show long-term survival with their native liver. However, most children eventually require liver transplantation (LTX). As several growth factors (GF) and chemokines have been shown to promote fibrogenesis in the liver, we assessed whether GF are predictive for the course of disease. Material and Methods: Liver and sera samples were collected from 49 infants with BA during KPE. Levels of 13 different GF were measured by multiplex immunoassay. Patient outcomes were stratified into favorable (bilirubin < 20 µmol/L at 2-year follow-up) and unfavorable (LTX). GF levels were compared between groups by a t-test, correlation coefficients were calculated, and principal component analyses performed. Results: Twenty-two patients showed a favorable and 27 an unfavorable disease course. No relation of GF and outcome could be established. In both groups, high levels of SDF-1alpha/CXCL12 (1473.0 ± 497.5 pg/mL), FGF2 (301.2 ± 207.8 pg/mL), and VEGF-a (209.0 ± 146.4 pg/mL) levels were measured within the liver, followed (in descending order) by PDGF-bb, LIF, GM-CSF, BDNF, VEGF-d, beta-NGF, IL-7, SCF, PIGF-1, and EGF. Serum marker levels showed much higher mean variation compared to hepatic values and no correlation to the protein microenvironment in the liver. Conclusions: Our study demonstrates high amounts of GF in livers from infants with BA at KPE, but no correlation to the outcome or serum values could be established. Our data suggest that local or systemic GF levels are unsuitable for prediction of the disease course. Collectively, we conclude that in BA the degree of proliferative activity caused by GF is a dismissible factor for the further course of disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia

Madadi-Sanjani

Froemmel

Falk

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…The level of BDNF was significantly decreased in serum samples of patients with cirrhosis due to biliary atresia and hepatitis. 33 , 34 Recently, a human study by Stawicka et al 35 presented serum levels of BDNF were decreased in cirrhosis patients with HE and introduced it as a diagnostic marker for HE. Furthermore, the protein and expression levels of BDNF were significantly decreased in the brain tissues of hyperammonemic animal models of HE.…”

Section: Discussionmentioning

confidence: 99%

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

Sepehrinezhad

Shahbazi

Negah

et al. 2023

Bioinform Biol Insights

View full text Add to dashboard Cite

Hepatic encephalopathy (HE) is a set of complex neurological complications that arise from advanced liver disease. The precise molecular and cellular mechanism of HE is not fully understood. Differentially expressed genes (DEGs) from microarray technologies are powerful approaches to obtain new insight into the pathophysiology of HE. We analyzed microarray data sets of cirrhotic patients with HE from Gene Expression Omnibus to identify DEGs in postmortem cerebral tissues. Consequently, we uploaded significant DEGs into the STRING to specify protein-protein interactions. Cytoscape was used to reconstruct the genetic network and identify hub genes. Target genes were uploaded to different databases to perform comprehensive enrichment analysis and repurpose new therapeutic options for HE. A total of 457 DEGs were identified in 2 data sets totally from 12 cirrhotic patients with HE compared with 12 healthy subjects. We found that 274 genes were upregulated and 183 genes were downregulated. Network analyses on significant DEGs indicated 12 hub genes associated with HE. Enrichment analysis identified fatty acid beta-oxidation, cerebral organic acidurias, and regulation of actin cytoskeleton as main involved pathways associated with upregulated genes; serotonin receptor 2 and ELK-SRF/GATA4 signaling, GPCRs, class A rhodopsin-like, and p38 MAPK signaling pathway were related to downregulated genes. Finally, we predicted 39 probable effective drugs/agents for HE. This study not only confirms main important involved mechanisms of HE but also reveals some yet unknown activated molecular and cellular pathways in human HE. In addition, new targets were identified that could be of value in the future study of HE.

show abstract

“…In liver disease, BDNF's neuroprotective actions against NMDA toxicity [100] may be compromised in hyperammonemia and HE conditions, which are associated with reduced BDNF and overactivation of NMDA receptors. In HE, serum BDNF is reduced in cirrhotic patients [102], while in cirrhotic-BDL rats with mHE, BDNF was found reduced in the hippocampus [103]. In hyperammonemic rats, hippocampal BDNF depletion is associated with a reduction of astrocyte BDNF production [104].…”

Section: Neuroplasticitymentioning

confidence: 96%

Hepatic Encephalopathy: From Metabolic to Neurodegenerative

2021

View full text Add to dashboard Cite

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of both acute and chronic liver disease. As a metabolic disorder, HE is considered to be reversible and therefore is expected to resolve following the replacement of the diseased liver with a healthy liver. However, persisting neurological complications are observed in up to 47% of transplanted patients. Several retrospective studies have shown that patients with a history of HE, particularly overt-HE, had persistent neurological complications even after liver transplantation (LT). These enduring neurological conditions significantly affect patient's quality of life and continue to add to the economic burden of chronic liver disease on health care systems. This review discusses the journey of the brain through the progression of liver disease, entering the invasive surgical procedure of LT and the conditions associated with the post-transplant period. In particular, it will discuss the vulnerability of the HE brain to peri-operative factors and post-LT conditions which may explain non-resolved neurological impairment following LT. In addition, the review will provide evidence; (i) supporting overt-HE impacts on neurological complications post-LT; (ii) that overt-HE leads to permanent neuronal injury and (iii) the pathophysiological role of ammonia toxicity on astrocyte and neuronal injury/damage. Together, these findings will provide new insights on the underlying mechanisms leading to neurological complications post-LT.

show abstract

Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia

Cited by 6 publications

References 28 publications

Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia

Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

Hepatic Encephalopathy: From Metabolic to Neurodegenerative

Contact Info

Product

Resources

About