Arteriohepatic dysplasia in infancy and childhood: a longitudinal study of six patients.

Abstract

Arteriohepatic dysplasia (syndromatic ductular hypoplasia, Alagille syndrome) is a condition of chronic cholestasis dating from infancy accompanied by characteristic facies, pulmonic stenosis, and other somatic abnormalities. The pathologic hallmark of arteriohepatic dysplasia is a paucity or absence of intrahepatic bile ducts, wildely regarded as a congenital deficiency. We present a longitudinal study of six infants and children with arteriohepatic dysplasia, stressing evolution of the characteristic pathology on liver biopsy. All patients were biopsied twice. All five liver biopsies performed during infancy (<6 months old) showed intrahepatic cholestasis and portal inflammation, and two infants had, in addition, giant cell transformation. No infant showed congenital absence of interlobular bile ducts. Three of five infants had normal numbers of interlobular bile ducts (0.5 to 1.0 interlobular bile ducts per triad) and two infants had a paucity of interlobular bile ducts (<0.5 per triad). Three infants showed focal destructive inflammation of interlobular bile ducts. All biopsies performed later in childhood, between 3 and 20 years of age, showed a paucity or absence of interlobular bile ducts. At this time cholestasis and inflammation had largely resolved but some fibrosis persisted. The number of interlobular bile ducts decreased with age in each patient but there was no characteristic age at which interlobular bile ducts disappeared completely. The presence of interlobular bile ducts in infancy followed later in childhood by paucity or absence of interlobular bile ducts, suggests that intrahepatic bile duct deficiency in some patients with arteriohepatic dysplasia is acquired rather than congenital. The mechanism of bile duct disappearance in these patients may have been destructive inflammation of duct epithelium. Histopathologic diagnosis of arteriohepatic dysplasia may be difficult or impossible in infancy since interlobular bile ducts may be present at that time. However, arteriohepatic dysplasia should be considered in the differential diagnosis of all infants with cholestasis and such infants should have careful clinical evaluation for the syndromatic features of arteriohepatic dysplasia. Evaluation of their liver biopsies should include specific morphometric assessment of interlobular bile ducts.