Serial liver biopsies in parenteral nutrition-associated cholestasis of early infancy.

Abstract The clinical course and liver biopsy pathology of 11 infants with parenteral nutrition (PN)-associated cholestasis were reviewed. All infants developed cholestatic jaundice shortly after beginning PN and had a liver biopsy at the height of clinical liver disease (average age 3 mo). The duration of PN averaged 1.5 mo (range 2 wk–6 mo). All infants showed a distinctive cholestatic hepatitis, with bile stasis in hepatocytes, canaliculi, and Kupffer cells, as well as portal inflammation, bile duct proliferation, and portal fibrosis. Two had ductular cholestasis and bridging fibrosis mimicking extrahepatic biliary atresia. In all patients except one, parenteral nutrition was discontinued after the first biopsy. Clinical and biochemical improvement was noted within 2 wk, and recovery appeared complete within 5 mo. Six of the patients had a second biopsy after recovery (average age 10 mo). All second biopsies showed complete resolution of portal inflammation and duct proliferation, but all 6 had mild persistent cholestasis, and 4 had periportal fibrosis and ultrastructural abnormalities, including collagen in the space of Disse and distinctive lamellar bodies. Parenteral nutrition was not discontinued in one infant with a short gut syndrome; he died of chronic liver disease at 5.5 mo of age, without a second biopsy. Thus, although infants with PN-associated cholestasis will recover if the infusion is discontinued, subtle abnormalities on liver biopsy persist months later. There was no relationship between severity of pathologic findings and duration of PN, total amino acid dose, or lipid administration. The etiology of liver damage in this condition is unknown, but there are some pathologic similarities to toxic liver disease.