Molecular signature of active fibrogenesis prevails in biliary atresia after successful portoenterostomy

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Kerola , A , Lampela , H , Lohi , J , Heikkilä , P , Mutanen , A , Jalanko , H & Pakarinen , M P 2017 , ' Molecular signature of active fibrogenesis prevails in biliary atresia after successful portoenterostomy ' , Surgery , vol. 162 , no. 3 , pp. 548-556 .

Title: Molecular signature of active fibrogenesis prevails in biliary atresia after successful portoenterostomy
Author: Kerola, Anna; Lampela, Hanna; Lohi, Jouko; Heikkilä, Päivi; Mutanen, Annika; Jalanko, Hannu; Pakarinen, Mikko P.
Contributor organization: Lastenkirurgian yksikkö
Children's Hospital
HUS Children and Adolescents
Department of Surgery
II kirurgian klinikka
HUS Abdominal Center
Department of Pathology
University of Helsinki
Lastentautien yksikkö
Date: 2017-09
Language: eng
Number of pages: 9
Belongs to series: Surgery
ISSN: 0039-6060
Abstract: Background. In biliary atresia mechanisms of progressive liver injury leading to need of liver transplantation after successful portoenterostomy remain unknown. A better understanding is a prerequisite for development of novel therapies to extend native liver survival, and we aimed to unravel molecular characteristics of liver injury after successful portoenterostomy. Methods. Liver biopsies obtained from 28 biliary atresia children during successful portoenterostomy and at median age 3.0 years were studied. Biopsies were analyzed for histology and immunohistochemical expression of collagen 1, myofibroblast marker alpha-smooth muscle actin, and cytokeratin-7 positive ductal reactions. Hepatic ribonucleic acid (RNA) expression of growth factors and inflammatory cytokines was evaluated. Intestinal failure patients with comparable liver fibrosis and nonfibrotic gallstone patients and donor livers were controls. Results. After successful portoenterostomy, histologic cholestasis resolved and portal inflammation reduced, while fibrosis along with ductal reactions and overexpression of collagen and alpha-smooth muscle actin persisted. At follow-up, liver RNA expression of collagen and platelet-derived growth factor was increased, whereas RNA expression of various inflammatory cytokines remained low. Disappearance of periductal alpha-smooth muscle actin expression after successful portoenterostomy (36% of patients) associated with contracted ductal reactions and reduced progression of fibrosis, collagen accumulation, platelet-derived growth factor RNA expression, and serum levels of bile acids and bilirubin. Fibrosis progressed less rapidly in syndromic than in isolated biliary atresia patients. Conclusion. These findings suggest that instead of inflammation, molecular signature of active fibrogenesis in association with ductal reactions prevails in long-term native liver survivors with biliary atresia. Patients should be stratified for isolated and syndromic disease forms in interventional studies.
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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