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To study the mechanism of the intrahepatic cholestasis observed during total parenteral nutrition (TPN) in neonates, we examined the localization of IgA, secretory component (SC) and complement component C3 (C3) in the liver in 4 patients by light and electron microscopic immunohistochemistry. In the patients who received TPN for 1 month, IgA- and SC-positive cholestasis was limited to bile canaliculi, but the integrity of both the canalicular wall and intercellular tight junction was maintained. These findings suggest that obstruction in the biliary tract develops at the canalis of Hering, causing reflux of IgA and SC into the bile canaliculi. When the duration of TPN extended beyond 6 months, the cholestasis in bile canaliculi progressed further, and degeneration of hepatocytes became more marked. Bile retained in hepatocytes occasionally contained IgA and SC. IgA- and SC-positive cholestasis also developed in the interlobular bile ducts, where no cholestasis had been observed 1 month after the beginning of TPN. SC production and SC-mediated transport of IgA, which are important functions of bile duct epithelial cells in the local immune mechanism, were impaired in association with the injury of those cells. C3 was localized not only in the hepatocellular organelles where C3 is normally observed, but also in the lumen of dilated bile canaliculi, suggesting that C3 is released from hepatocytes into bile in neonates receiving TPN and that C3 may be involved in some local immune mechanism of biliary system.

keio journal of medicine

Immunoelectron Microscopic Study on IgA, Secretory Component and Complement Component C3 in the Liver of Children Undergoing Total Parenteral Nutrition through Neonatal Period.