LAUSR

Alagille syndrome (AGS), a multisystem disorder, is caused by defects in the Notch signalling pathway with an autosomal dominant inheritance [1]. The main organ systems affected are the liver (chronic cholestasis ± bile duct paucity), heart (congenital heart disease primarily affecting the pulmonary outflow tract and vasculature), skeletal system (butterfly vertebrae, hemivertebrae, fusion of adjacent vertebrae, recurrent fractures), eyes (posterior embryotoxon, optic disc abnormalities and wide variety of abnormalities affecting the cornea, iris, retina, optic disc), kidneys (structural anomalies, renal tubular acidosis) and vasculature (anomalies of blood vessels especially in brain) along with characteristic facial features [1, 2]. AGS can be diagnosed clinically on the basis of cholestasis with at least three features from the list of characteristic Alagille facies, congenital cardiac disease, posterior embryotoxon, butterfly vertebrae, typical renal disease and a structural vascular anomaly [3]. If genetic mutation is identified, then the presence of a single clinical feature is sufficient to diagnose AGS [3]. AGS patients have an increased risk of developing wide variety of liver tumours including nodular hyperplasia of the liver, adenomas, hepatoblastoma and HCC [3, 4]. Hepatocellular carcinoma (HCC) is a rare long-term complication of AGS in adults but is being increasingly reported in children [5–8]. There is increased risk of HCC across all age groups [6, 7]. HCC in AGS can occur with or without the presence of cirrhosis [3]. JAGGED 1 and NOTCH 2 upregulation or activation has been noted in mouse models of HCC favouring a role for these genes in development of HCC [8]. We present our experience with 3 cases of HCC in AGS and review of literature for HCC in paediatric patients with AGS.