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On the Pathogenesis of Central Liver Nodules in Alagille Syndrome

Libbrecht, Louis*,†; Cassiman, David*,‡,§

Journal of Pediatric Gastroenterology and Nutrition: March 2017 - Volume 64 - Issue 3 - p e80
doi: 10.1097/MPG.0000000000001468
Letters to the Editor

*Liver Research Unit, University of Leuven, Leuven, Belgium

Department of Pathology, University Hospital Saint-Luc, Brussels, Belgium

Department of Gastroenterology and Hepatology

§Metabolic Center,University Hospitals Leuven, Leuven, Belgium.

Alhammad et al (1) described central hyperplastic liver nodules in Alagille syndrome patients and Rougemont et al (2) proposed that vascular anomalies lead to the development of central liver nodules with intact bile ducts, while bile duct integrity is affected in the peripheral liver.

Based on our findings in the explant liver of an Alagille syndrome patient, we proposed that defects in postnatal bile duct branching and elongation lead to bile duct paucity in the peripheral liver, while normal bile ducts are present in the central portion (3). Our hypothesis was supported in an animal model (4).

Although bile duct paucity causes cholate statis in the liver periphery, intact bile ducts in the central portion prevent the accumulation of hepatotoxic bile salts (3). This leads to compensatory hyperplasia of the central liver, yielding the picture of a hyperplastic regenerative nodule. This hyperplasia will be associated with changes in the vasculature, so we propose that the vascular anomalies are secondary to the biliary anomalies and not vice versa.

We speculate that the growth advantage in the central liver can lead to the development of hepatocellular carcinoma. It has been shown in transgenic mouse models that hepatocellular carcinoma arises from liver nodules resistant totoxic products in these models (5,6). Wetli et al (7) described hepatocellular carcinoma next to a central regenerating nodule. Because our suggestion is currently speculative, we propose that extra attention should be paid to the relative location of hepatocellular carcinomas and regenerative liver nodules in Alagille syndrome.

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1. Alhammad A, Kamath BM, Chami R, et al. Solitary hepatic nodule adjacent to the right portal vein: a common finding of Alagille syndrome? J Pediatr Gastroenterol Nutr 2016; 62:226–232.
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© 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,