Brief Article
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World J Gastroenterol. Mar 28, 2014; 20(12): 3312-3319
Published online Mar 28, 2014. doi: 10.3748/wjg.v20.i12.3312
Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia
Janne S Suominen, Hanna Lampela, Päivi Heikkilä, Jouko Lohi, Hannu Jalanko, Mikko P Pakarinen
Janne S Suominen, Hanna Lampela, Mikko P Pakarinen, Department of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children’s Hospital, University of Helsinki, 00290 Helsinki, Finland
Päivi Heikkilä, Jouko Lohi, Department of Pathology, HUSLAB, Helsinki University Central Hospital, 00290 Helsinki, Finland
Hannu Jalanko, Department of Paediatrics, Children’s Hospital, Helsinki University Central Hospital, 00290 Helsinki, Finland
Author contributions: Suominen JS analyzed the immunohistochemistry; Heikkilä P and Lohi J evaluated the histological fibrosis scores; Lampela H gathered the clinical data on patients; Jalanko H and Pakarinen MP designed the study and all authors took actively part in the writing process.
Supported by Sigrid Juselius Foundation; and the Finnish Pediatric Research Foundation
Correspondence to: Janne S Suominen, MD, PhD, Department of Paediatric Surgery, Pediatric Liver and Gut Research Group, Children’s Hospital, University of Helsinki, Stenbäckinkatu 11, 00290 Helsinki, Finland. janne.suominen@hus.fi
Telephone: +358-5-4270746 Fax: +358-9-47175314
Received: October 2, 2013
Revised: November 27, 2013
Accepted: January 3, 2014
Published online: March 28, 2014
Processing time: 175 Days and 21 Hours
Abstract

AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.

METHODS: Liver specimens were obtained at PE from 33 biliary atresia (BA) patients for immunohistochemical analysis of collagen 1, α-SMA and CD34. Liver biopsies from 35 organ donors were used as controls. Expression patterns were related to clinical data including age at PE, serum total and conjugated bilirubin concentration at the time of PE and during follow-up, incidence of esophageal varices in follow-up upper gastrointestinal endoscopies, and native liver survival as well as to detailed histopathological findings.

RESULTS: Collagen 1 (16.4% vs 4.5%, P < 0.0001), α-SMA (17.9% vs 4.6%, P < 0.0001) and CD34 (4.9% vs 3.8%, P = 0.017) were markedly overexpressed in BA patients compared with controls. Patients who underwent liver transplantation by age of two years had significantly higher expression of collagen 1 (18.6% vs 13.7%, P = 0.024), α-SMA (20.4% vs 15.4%, P = 0.009) and CD34 (5.9% vs 4.0%, P = 0.029) at PE compared with native liver survivors. CD34-positive microvessels were identified in the centrizonal region close to central vein in every BA patient. In majority of BA cases (56%) neovascularization was frequent as CD34-positive microvessels were observed in over half of the hepatic lobules. In controls, the CD34-positive microvessels were rare as they were completely absent in 40 % and were found in less than 5 % of the hepatic lobules in the rest. The difference between BA patients and controls was significant (P < 0.0001). Patients who developed esophageal varices by two years had significantly higher expression of CD34 at PE compared with patients without varices (5.6% vs 4.0%, P = 0.019). Expression of α-SMA (r = 0.758, P < 0.0001) and collagen 1 (r = 0.474, P = 0.016), and the amount of CD34-positive microvessels (r = 0.356, P = 0.047) were related to patient age at PE.

CONCLUSION: Hepatic myofibroblastic cell activation, fibrogenesis and neovascularization are enhanced in BA, progress with increasing PE age and relate to native liver survival and development of esophageal varices.

Keywords: Biliary atresia; Liver fibrosis; Neovascularization; Collagen 1; α-smooth muscle actin; CD34

Core tip: The majority of biliary atresia (BA) patients require liver transplantation (LTx) due to progressive hepatic fibrosis and associated portal hypertension. We aimed to relate expression of collagen 1, α-smooth muscle actin (α-SMA) and CD34 to the most essential portoenterostomy (PE) outcomes. Collagen 1, α-SMA and CD34 were markedly overexpressed in BA patients compared with controls and centrizonal neovascularization was increased in BA. Patients who underwent LTx by age of two years had significantly higher expression of collagen 1, α-SMA and CD34 at PE compared with native liver survivors. Fibrogenesis and neovascularization are enhanced in BA, progress with increasing PE age and relate to native liver survival and development of esophageal varices.