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Neonatal intrahepatic cholestasis is a heterogeneous disease of undetermined cause. There is an unreported subset of idiopathic neonatal intrahepatic cholestasis with an unusual histological combination of hepatic siderosis and macrovesicular steatosis. The patients were a 34-day-old female and a 39-day-old male with normal birth weights. Their mothers had received oral iron supplement 4-6 weeks before delivery. The patients had obstructive jaundice noticed at the well-baby clinic at 1 month of life. They had high levels of serum galactose and tyrosine, hyperferritinemia. Urinary organic acid and bile acid analyses were negative, and galactose-1-phosphate uridyltransferase activity in red cells was normal. Liver biopsies showed diffuse iron deposits and macrovesicular fat. By substituting formula milk with lactose-free milk, the patients responded, and had normal biochemical tests within 5 months of life. Follow-up biopsies, at the age of 12 months, showed mild residual fibrosis without iron or fat deposits. They are both well at 3 and 6 years of age, respectively, without biochemical liver dysfunction and neurologic impairment. Prenatal iron-overload might contribute to the pathogenesis of the disease, but further studies are needed to confirm the assumption.

To clarify the relationship between idiopathic neonatal hepatitis and feeding type, that is, formula-milk feeding and breast-milk feeding, the medical records of 100 patients (68 male and 32 female babies) with idiopathic neonatal hepatitis of non-familial form referred to the medical centers of Akita University and Tohoku University during the past 18 years were reviewed. The patients were divided into two 9 year periods (1975–83 and 1984–92), and their clinical features were analyzed in terms of feeding type and sex. The number of patients enrolled decreased from 69 in the first half to 31 in the second half. The number of male patients dropped from 53 to 15, although the number of female patients (n = 16) remained the same in both 9 year periods. The frequency of formula-milk feeding significantly decreased in the second half (42/69 to 6/31, P < 0.01). Compared with the expected numbers of patients in the second half, calculated on the changes in the live birth population and feeding modality between the two halves, the actually enrolled numbers of patients in the second half were less in both the male and the formula-milk fed groups (× 0.35 and × 0.22), whereas the numbers of female and breast-milk feeding groups were close to the expected values (× 1.26 and × 1.08). When sex and feeding modality were combined, the formula-milk fed male group showed the lowest value (× 0.10), and the breast-milk fed female group showed the highest value (× 2.85). In conclusion, feeding type, especially in combination with gender, might be one causative factor in the occurrence of idiopathic neonatal hepatitis.

Idiopathic neonatal hepatitis (INH) is a syndrome characterized clinically and histologically but there is little information concerning the relationship between the clinical features and histological findings. In the present study, sixty-two patients clinically diagnosed as non-familial INH were histologically classified into four groups according to a provisional definition based on predominant lesions and examination of their clinical features. Patients of cholestasis (n = 23) and giant cell hepatitis (GCH, n = 21) were most frequent (37% and 33%, respectively), and patients of fatty liver (n = 10) and hepatitis (n = 8) were less common (16% and 13%). The GCH group showed a dominance of male, low birthweight, older and breast-fed babies. The cholestasis group demonstrated a dominance of male, low birthweight, younger and bottle-fed babies. The hepatitis group had the highest frequencies of high-grade hepatomegaly and splenomegaly. Fifty six cases completely recovered. Two died of hepatic failure in early infancy and four had chronic liver diseases at the age of 12 months. The fatty liver group had the worst outcome. Histological features in non-familial INH were variable and typical giant cell hepatitis was seen in only one-third of patients. Characteristic clinical features in each histologically classified group may suggest heterogenous etiologies underlying non-familial INH.