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

Abstract

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.

Systemic cytokine profiles in biliary atresia

“…In contrary to the above findings, reductions in plasma levels of growth factors including PDGF and VEGF were observed to be significantly associated with the presence of BA and jaundice. These findings have been supported by previous clinical studies revealing significant alterations in plasma levels of several growth factors in BA patients compared to healthy controls [10]-particularly a significant decrease in plasma VEGF levels [24]. In hepatitis B virus (HBV)-infected patients, the severity of liver damage and fibrosis was found to be associated with plasma PDGF levels [25], consistent with our additional findings showing associations between plasma levels of VEGF as well as PDGF and clinical parameters, especially liver stiffness in BA patients.…”

Post-hepatoportoenterostomy Acoustic Radiation Force Impulse Elastography to Predict Two-year Outcome of Biliary Atresia

“…3 Although effective HPE treatment can reestablish bile drainage and greatly improve prognosis, most patients still have continuous inflammation and fibrosis postoperatively and require LT for long-term survival, which accounts for nearly 50% of all pediatric transplants. 4,5 However, hepatic fibrosis progression and complications of portal hypertension after HPE lead to a need for LT, which is heterogeneous and unpredictable. An early prognostic indicator for post-HPE disease dynamics is crucial to the management of BA patients because late referral for LT could cause pediatric mortality due to the scarcity of donor organs, especially for infants.…”

“…An early prognostic indicator for post-HPE disease dynamics is crucial to the management of BA patients because late referral for LT could cause pediatric mortality due to the scarcity of donor organs, especially for infants. 5,6 Although many investigators have examined prognostic factors to identify short-or long-term outcomes of HPE for infants with BA in the early stages, only a few markers may be indicative of the ultimate success of HPE, such as patient age and initial aspartate aminotransferase to platelet ratio index (APRI) at the time of surgery. 1,[7][8][9][10] Recent reports indicate that postoperative bilirubin levels are markedly associated with native liver survival (NLS) in children.…”