Electron microscopic study of the liver with biliary atresia and neonatal hepatitis

Eleven cases of biliary atresia (BA) and eight of neonatal hepatitis (NH) were studied, using transmission electron microscopy, to document their different ultrastructural characteristics and to elucidate the possible pathogenesis of biliary atresia. Among 30 consecutive liver biopsies obtained from 19 infants with BA or NH, 21 specimens composed (13 BA, 8 NH) were examined ultrastructurally. The electron microscopic features of NH (patients' age range, 35 to 60 days) were (1) giant hepatocytic transformation with scattered areas of dilated endoplasmic reticulum, indicative of intracytoplasmic degeneration, (2) frequent cytoplasmic biliary necrosis, and (3) relatively intact microvilli in most bile canaliculi, which contained some hepatocytic cytoplasmic fragments. These features strongly suggest that the main pathological process in NH is hepatocellular injury rather than bile duct damage. In contrast, all cases with BA (age range, 27 to 130 days) demonstrated (1) marked hepatocellular cholestasis associated with many lysosomes and myelin figures, (2) marked loss of bile canalicular microvilli, (3) degenerated bile ductular cells containing bile pigments, and (4) periductal inflammatory fibrosis. These features suggest that the main pathological process in BA involves the biliary system. A few viral inclusions were observed in two cases with BA, which suggests that viral infection is a potential cause. In two BA cases (aged 40 and 43 days at the time of first biopsy), the ultrastructural findings essentially were the same as those of NH, and follow-up biopsy specimens (at 48 and 94 days) showed findings consistent with BA. Such results support Landing's hypothesis that BA and NH are different manifestations of a single pathological process.