Fulminant hepatitis associated with centrilobular hepatic necrosis in young children.

Abstract

To describe fulminant hepatic failure (FHF) in children in the United States with clinical and histopathologic features distinctly different from those typical of FHF. Seven young children were seen in early 1994 with encephalopathy, coagulopathy, and elevated aminotransferase levels. Liver failure was preceded by a prodromal viral illness that resulted in a period of fasting without dehydration. Unlike the majority of children with FHF, these patients had serum bilirubin levels < 171 mumol/L (10 mg/dl). All children had received therapeutic doses of acetaminophen during the prodromal illness. Histologic findings included zonal necrosis of hepatocytes in a centrilobular distribution, which is characteristic of toxic liver injury but is atypical for viral hepatitis and sporadic non-A non-B hepatitis. Six patients recovered spontaneously, and one died of complications of liver failure and fungal sepsis. The cause of this disorder remains unknown, but we postulate a viral or environmental insult that preferentially damages zone 3 hepatocytes. The potential for this injury may have been augmented by ingestion of therapeutic doses of acetaminophen while patients were in a fasted state. The prognosis was good compared with typical FHF in children and correlated with the degree of liver necrosis on histologic examination.